O. Kovalsky De Ietent SV V. Danylevych RAD. Diagnostic Imaging ap CUBS 35MINISTRY OF HEALTH OF UKRAINE O. Kovalsky D. Mechev V. Danylevych RADIOLOGY RADIOTHERAPY DIAGNOSTIC IMAGING Textbook for students of higher medical educational establishments of IV" accreditation level IReningicaurtnHiA Kon BIBJIOT 16478309 EKA Vinnytsia Nova Knyha 2013YAK 615.849(075.8) Pexomendosano Minicmepcmaox oxoponu sdopos'a Vipainu ax BBK 53.6873 nidpynux daa cmydexmis euujux meduanuex Hasuatonux saKradi6 K 56 IV piana axpedumayit (npomokon Ne 3 id 16.10.2012 p. sacidanna Konicil 3 meduyunu nayKoeo-memodunot padu 3 numan oceimu Minicmepemea oceimu i nay, mon0di ma cnopmy Yepainu) Tpup Minicmepemea oxoponu sdopos'a Vepainu eudanuii na yxpaivomosne eudanna. Tlanuit nidpyanun € neperiadon 3 yxpaincexol woot. Authors: Kovalsky 0. V. — Candidate of Medical Sciences, Associate Professor manag- ing the Course of Diagnostic Radiology and Radiotherapy, Vinnytsia National Pirogov Memorial Medical University. Mechev D. S. — Honored Scientist of Ukraine, Doctor of Medical Sciences, Professor, Chief of the Radiology Department, P.L. Shupik National Medical Academy of Post. Graduate Education. Danylevych V, P. — Assistant of the Course of Diagnostic Radiology and Radiotherapy, Vinnytsia National Pirogov Memorial Medical University. Reviewers: A. A, Honchar, Doctor of Medical Sciences, Professor of the Rocntgenology Department, P. L. Shupik National Medical Academy of Post-Graduate Education V. M. Rychyk, Honored Scientist of Ukraine, Doctor of Medical Sciences, Professor, Chief of the Radiology Department, Ivano-Frankivsk National Medical University. V.M. Sokolov, Honored Scientist of Ukraine, Doctor of Medical Sciences, Professor of the Oncology Department with the Course of Diagnostic Imaging and Radiotherapy. Odessa National Medical University, Kovalsky O. V. K56 Radiology. Radiotherapy. Diagnostic Imaging : textbook for stud. of higher med. establishments of IV" accred. level : translated from Ukrainian / O. Kovalsky, D, Mechev, V. Danylevych. — Vinnytsia : Nova Knyha, 2013, — 496 p. sil. ISBN 978-966-382-480-2 The textbook for students of higher medical educational establishments was created in accordance with the program for the discipline “Radiology” (Kyiv. 2006) and complies with the principles of the European credit-modular system for the high-quality training of doctors. In the textbook there are represented the most recent achievements of Medical Radiology, Diagnostic Imaging techniques and its principles, diagnostic imaging of internal organs diseases, diagnostic algorithms in the study of organs and systems, questions for self-control and case studies. For the convenience of students the current level of radiation therapy is presented in one publication For students of higher medical educational establishments of IV" accreditation radiologists and physicians of other specialties. level. int YAUK 615.849(075.8) BBK 53.6273 Koyalsky O. V., Mechev D. S., Danylevych V. P., 2013 ISBN 978-966-382-480-2 © Nova Knyha, 2013CONTENT Introduction... Abbreviations... Part |. Fundamentals of Medical Radiology Chapter 1. Principles of Medical Radiology... Chapter 2. Biological Effects of lonizing Radiation.. Part Il. Radiotherapy Chapter 3. Principles and Fundamentals of Radiation Therapy of Malignant Tumors and Non-Neoplastic Lesions... 39 Chapter 4. X-ray Therapy. ss Chapter 5, Long-Focus Radiotherapy... Chapter 6. Brachytherapy... Part Ill. Methods of Diagnostic Imaging. The Physical Basis of Diagnostic Imaging Chapter 7. Nuclear |maging.......... Chapter 8. X-ray, CT, MRI and Uitrasound Imaging Part IV. Diagnostic Imaging of Organs and Systems Diseases Chapter 9. Diagnostic Imaging of the Skeleton... Chapter 10, Diagnostic Imaging of the Chest... Chapter 11. Diagnostic Imaging of the Cardiovascular System Chapter 12. Diagnostic Imaging of the Digestive System Chapter 13. Diagnostic Imaging of the Urinary System... Chapter 14. Diagnostic Imaging of the Reproductive System and Breast... sma Chapter 15. Diagnostic Imaging of the Central Nervous System Chapter 16. Diagnostic Imaging of the Endocrine Glands Chapter 17. Diagnostic Imaging in Dentistry... References...INTRODUCTION Radiology is the medical discipline which includes Diagnostic Radiology and Radiation Therapy. Diagnostic Radiology studies the use of ionizing radiation, ultrasound and magnetic fields to diagnose diseases of organs and systems. Radiotherapy studies the use of ionizing radiation for the treatment of ma- lignant tumors and non-neoplastic lesions. The textbook “Radiology” for medical students is consistent with the prin- ciples of the European credit-modular system for qualitative changes of future physicians according to the program for the discipline ‘Radiology’ (Kyiv, 2006). The order of the training materials in the issue is related to the need of stu- dents (the initial acquaintance with the “Radiology” — dosimetry of ionizing ra- diation, biological effects of ionizing radiation, radiation safety). in the first part — "Fundamentals of Medical Radiology °— there are repre- sented the foundations of Medical Radiology, dosimetry of ionizing radiation, biological effects of ionizing radiation. In the second part — “Radiotherapy” — there are described the principles, methods and elements of radiotherapy of malignant turnors and non-neoplas- tic lesions. The third part — “Methods of Diagnostic Imaging’ — presents the physical principles of Diagnostic Radiology. The fourth part — ‘Diagnostic Imaging of Organs and Systems Diseases” — shows the possibility of X-ray, CT, MRI, ultrasound, nuclear imaging and inter- vention methods. The section “Diagnostic Imaging in Dentistry’ includes the modern methods of Diagnostic imaging of teeth and jaws, Radiological Anatomy and Diagnostic Imaging of Dental Pathology according to the program “Radiology (Diagnos- tic maging and Radiation Therapy’ (Kyiv, 2011) for students of stomatological departments of higher medical educational establishments of IV” accreditation level.ABBREVIATIONS AFP —c-fetoprotein Bq — Becquerel BSRU —Basic Sanitary Rules of Work with lonizing Radiation in Ukraine CEA = —carcincembryonic antigen cm —centimeter CM = —contrasting matter CNS = —central nervous system CPS —calices-pelvis system cT — computed (X-ray) tomography ci — Curie DMSA —dimercaptosuccinic acid DNA —deoxyribonucleic acid EOA — electro-optical amplifier ESR — erythrocyte sedimentation rate eV —electron-volt EU — excretory urography Fig. = —figure 9 —gram GIT — — gastrointestinal tract Gy —Grey Hb = —hemoglobin HSA = — human serum albumin HU — Hounsfeld units IRMA — immunoradiometric assay kv — kilovolt LFRT © —long-focus radiotherapy mA — —milliampere MH — — Ministry of Healthcare min — minute mm = —millimeter MRA —— magnetic resonance angiography MRI — magnetic resonance imaging NI — nuclear imaging NRSU = — norms of radiation safety of Ukraine PET — positron emission tomographyRAW = —radioactive wastes RCP = — retrograde cholangiopancreatography RD — roentgenologic diagnostics RIA — radioimmunoassay RP — radiopharmaceutical preparation SCT —spiral X-ray) computed tomography sec — second SFD —single focal dose SPECT — single-photon emission computed tomography SSD = —source-skin distance Sv — Sievert TAUS — transabdominal US TFD = —total focal dose Tg — thyroglobulin TRUS = — transrectal US TTH — thyrotropic hormone TVUS = — transvaginal US US — ultrasound diagnostics (ultrasound examination) WBC — white blood cells WR — radiation suspended factorfear oP Fundamentals of Medical Radiology Chapter J. Principles of Medical Radiology Chapter 2. Biological Effects of lonizing RadiationPRINCIPLES OF MEDICAL RADIOLOGY Radiology is a section of medicine which works out the theory and practice of using ionizing radiation for diagnostics (radiodiagnostics) and treatment (ra- diotherapy). Radiodiagnostics studies the use of radiations for the evaluation of different organs and systems structure and functions. Radiodiagnostics includes: X-ray diagnostics, nuclear imaging (NI), ultrasound diagnostics (US), computed to- mography diagnostics (CT), magnetic-resonance imaging (MRI), interventional radiology. Radiotherapy studies the use of ionizing radiation for the treatment of on- cologic and non-oncologic diseases. At the end of the 20" century all the methods of diagnostics and treatment based on the use of ionizing radiations, ultrasound, infra-red radiation, mag- netic fields of atomic nuclei were united into a single scientific speciality — Radiology. THE HISTORY OF MEDICAL RADIOLOGY The discovery of X-rays must be considered as one of the fastest known discoveries in the world. Wilhelm Conrad Roentgen (1845-1923), a German physicist, was Professor of Physics at (Munich) Wurzburg University. He began his experiments on X-rays in the late October of 1895, which ultimately yielded ‘the actual experimental discovery on the 8" of November, 1895. However, he announced about it in press on the 28" of December, 1895. The discovery was made known to the world on the 5" of January, 1896. Clinically, the first medi- cal radiograph was produced in Great Britain by A. A. Campbell Swinton and J.C. Stanton on the 13" of January, 1896. Although the prospects for the X-ray diagnostics were immediately recognized, Roentgen refused to enter any com- mercial contract to exploit his discovery. He was of the opinion that his discov- ery belonged to the humanity and should not be the subject of patents, licens- es and contracts. The first Nobel Prize for Physics was awarded to him in 1901.Antoine Henri Becquerel (1852-1908) Wilhelm Conrad Roentgen (1845-1923) In 1896 Antoine Henri Becquerel, a French scientist, discovered natural ra- dioactivity (the second notable event). Radioactivity is a decay of unstable nuclei giving off radiation until they become stable, for example: 778Rq > $He+ U2Rn+ The materials which emit ionizing radiation are named radioactive materials. In 1896 Marie and Pierre Curie isolated polonium and radium out of ura- nium ore. In 1934 Irene and Frederic Joliot-Curie discovered artificial radionuclides (radionuclides or isotopes) — varieties of elements with an identical proton number in the nucleus but a different quantity of neutrons, thus having the same order number in Mendeleev's periodic table, but a different mass. Artifi- cial radionuclides (radionuclides) are received in nuclear reactors while bom- barding stable chemical elements by neutrons or elementary particles in ac- celerators of elementary particles. The nuclei of radionuclides decay with the release of ionizing radiation, for example: 31p 4 Ip _y 32 32 2 iP + gn oP St 4e The adioactivity determined by natural radionuclides is named natural, while the radioactivity determined by artificial radionuclides is named artificial. In 1940 G. N. Flerov and K. O. Petrzhak discovered the phenomenon of in- dependent decomposition of uranium nuclei into large fragments which is accompanied by releasing of two-three neutrons able to cause subsequentdivision of other uranium nuclei. This discovery became the basis for the reali- zation of the chain reaction. In 1942 Enrico Fermi in Chicago (USA) first built an operating atomic reactor. In the process of the work of the reactor they got the raw material for making a-bombs, and in 1945, for the first time in history, the energy of an atomic nucleus was used to the humanity harm — a-bombs were thrown on the Japanese cities Hiroshima and Nagasaki by American pi- lots, which caused death of more than 300 thousand people. The use of atomic weapon became a shove to the stormy development of Radiobiology — the science which studies biological effects of ionizing radia- tion. Radiobiology includes: Radiation Hygiene, Radiation Biochemistry, Radia- tion Genetics, Radiation Cytology, Radiation Immunology, Radiation Ecology, Space Radiobiology, Radiobiology of Tumors, Prophylaxis and Treatment of Radiation Defects. PHYSICAL BASE OF RADIOLOGY The structure of an atom The atomic nucleus consists of protons, neutrons and other elementary par- ticles which are kept together due to the forces of nuclear attraction. The pro- tons and neutrons sum makes the mass number of chemical elements. Around the nucleus negatively charged electrons rotate. The number of protons in the nuclear equals to its number in Mendeleev's periodic system. Atomic nuclei of heavy elements are unsteady and beginning with the 84" element turn into other nuclides. The types of radioactive interaction 1. Alpha-decay is an release of alpha-particles (#He) out of the nuclei of natural radioactive elements: 26 “Ho + pn 4+ agRa > >He+ *gRn+y 2, Electronic nuclear beta-decay is a release of beta-particles (electron, °¢) out of natural or artificial radioactive elements: 40, 40 -1 ik > Catyt+e3. Positron nuclear beta-decay is a release of beta-particles (positron, Je) out of natural or artificial radioactive elements: os a 7 3020 > Cut y+e 4, K-capture (orbital electron capture) — a nuclear proton captures an electron from the K-layer (the nearest level to the nuclear one) and turns into a neutron. The order number of the element diminishes by one. An electron from another layer passes to the vacant place in the K-layer which is accompa- nied by releasing of the characteristic radiation quantum: 4 1 _y 64 yy Cute — 33Ni+v 5. A spontaneous decay of nuclei is observed in the radioactive elements with a great atomic number (#°U, Pu, etc.) if their nuclei are captured by slow neutrons: 235) 4 yyy Kp 4 tnd QU + p> spk + SeBat ont nt+E A nuclear decay is accompanied by a release of nuclear energy. Neutrons (which emerge at a decay of nuclei) cause a decay of other nuclei (nuclear chain reactions). 6. Thermonuclear reactions (synthesis of nuclei) emerge if the temperatures achieve several million degrees. At this rate the nuclei of light elements are united into the nuclei of heavier elements: 20437 > tHe+ |n+E(17,57MeB) The law of the radioactive decay permanence: in regular intervals of time there occurs a nuclear transformation of equal parts (portions) of radionuclide active atoms: ~at Noe Where N, is the number of active atoms at the initial moment (t=0); N, is the number of the radioactive atoms which remained in the time of t; e is the decay constant which is determined by the part of the atoms which decay per time unit. "The part of the atomic nuclei which decay is the constant for every radionuclide named the decay constant ()): where T (the half-decay period) is the time during which the half of the active atomic nuclei of this radionuclide decay. Radionuclides with the period of half- decay more than 15 days are considered to be long-living radionuclides, less than 15 days — short-living radionuclides, Radioactive substance activity is the number of nuclear interaction per time unit. The SI unit of activity is becquerel (Bq) — one transformation per second; MBq= 10° Bq, GBq= 10° Bq, TBq= 10" Bq). The off-system unit of ac- tivity is curie (Ci). 1 Ci=3.7x 10" Bg, the derivatives of Ci: millicurie (mCi) = 3.7x 10” Bq; microcurie (mcCi)=3.7 x 10¢ Bq. lonizing radiation is the radiation which at interacting with a material causes the excitation of the material atoms and molecules and leads to the emerging of oppositely charged ions. The types of ionizing radiations: * corpuscular: alpha-radiation, beta-rays, proton radiation and neutron radiation; * quantum or photonic: gamma-radiation (electromagnetic radiation that arises up during the transformation of radioactive nuclei or during the interaction of the fast charged particles with the material), X-rays (braking radiation) and space radiation. The properties of ionizing radiations: 1) the penetrating property is the ability of ionizing radiation to get through different materials (inversely proportional to the material density); 2) the ionizing property is the ability of ionizing radiation to split mole- cules into positively and negatively charged ions, for example: H,O= H*+OH; 3) the photochemical property — is the ability of ionizing radiation to cause photolysis AgBr = Ag* + Br (used while exposing photographic materials);4) the luminescent (scintillation) property — is the ability of ionizings ra- diation to cause scintillations (luminescence) of some chemical materials; 5) the biological property is the ability of ionizing radiation to cause func- tional, anatomic and metabolic changes at various levels of the bio- logical organization (the molecular, subcellular, cellular, organ systems level and organismic level); 6) the cumulative property is the ability of ionizing radiation to accumu- late negative effects of radiation exposures in the organism, which even- tually can cause undesirable remote consequences (malignant tumors, congenital malformations, gene mutations, life-span reduction); 7) the thermal property is the ability of ionizing radiation to be accompa- nied by thermal energy release. lonizing radiations are not perceived by sense organs, they are invis- ible, do not have either smells or taste, that is why at the moment of radiation exposure the organism does not feel its effect. In medical practice there are used both ionizing (alpha-, beta-, gamma-, X-ray, neutron and proton) and non-ionizing (ultrasound, infra-red, laser, reso- nant radio-frequency) radiations. Sources of ionizing radiations. They distinguish natural sources — space radiation and natural radionuclides of the Earth and artificial sources of ion- izing radiation — non-radionuclide and radionuclide. Non-radionuclide (non-nuclear) sources are technical devices which do not contain radionuclides, but under certain conditions are able to generate ionizing radiation due to the acceleration and deceleration of charged parti- cles. These are generators of X-ray (X-ray short- and long-focus apparatuses), deceleration and corpuscular radiations of high energies (linear accelerators of electrons, betatrons, synchrophasotrons, synchro-cyclophasotrons, etc,). Radionuclide (nuclear) sources are sources in which the radioactive mate- rial has a continuous effect. Depending on a technological setting they distin- guish closed and open sources of ionizing radiations. A closed source is a radioactive radiant the equipment of which prevents the hit of radioactive material that is contained in it to the external environ- ment, for example; radioactive preparations (needles, beads, etc.) and a gam- ma therapy device for static and dynamic radiation exposure. An open source is a radioactive radiant at the use of which there is possible a hit to the external environment of a radioactive material, that is in it there are contained real solutions and suspensions of a radioactive material. 13The physical properties and penetrability of some ionizing radiations are represented in Table 1.1. Table 1.1. The physical properties and penetrability of some types of ionizing radiations Radia- | Energy of | Speed of dis-/ Path __| Path length | tonizing power (den- tion | radiation | tribution in | length in | intissues | sity of ionization ofMeV | the vacuum | the air per unit of the path of km/c length in the air) Alpha | 1-10 20.000 | to20cm | toS50mkm | 10.000-20.000 ion pairs/mm Beta_| 01-2 | 270.000 | to1sm | totem | S-10ionpairs/mm Gamma | 0.1-20 | 300.000 | hundreds | tens of Lion pair/em ofmeters | centimeters Neu- 0.5-10 0.001— hundreds | centimeters, hundreds, tens of trons 1.000.000 | ofmeters | meters "| thousands of ion pairs per mm. The material - ionizing radiation interaction The primary mechanisms of material-ionizing radiation interaction are the excitation of the atom or its ionization as a result of transferring the radiation energy to the atomic electron. Depending on the magnitude of linear energy transmission (LET), all ionizing radiations are divided into rarely- and densely-ionizing radiations. To the rare- ly-ionizing radiations belong the radiations with LET less than 10 keV/mkm — B- and quantum radiations. The densely-ionizing radiation has LET more than 10 keV/mkm — neutrons, protons, nuclei of heavy chemical elements. Different types of radiations cause different types of ionization. Primarily-ionizing radiations transfer their ionization to the medium directly by charged particles (a-, B-particles, protons, heavy ions, m-mesons). Quantum radiations (X-ray and y-radiation) and neutron radiation belong to secondary ionizing radiations. The material - ionizing quantum radiation interaction At the material - ionizing quantum radiation interaction the following ef- fects emerge: 141. The photoelectric effect (photo effect) comes as a result of transmis- sion of the whole quantum energy to the orbital electron (the energy of quantum is 0.1-0.3 MeV). 2. The Compton effect (Compton dispersion) consists in the transmission of part of the y-quantum energy to the electron and changing its initial direction (the energy of quantum is 0.1-0.3 MeV). . Formation of electrons-positrons pairs emerges as a result of colli- sion of a photon with the nucleus (the photon energy is more than 1 MeV). we The material - ionizing corpuscular radiation interaction At the interaction of a-particles with a material there emerges the excitation and ionization of atoms as a result of inelastic collisions with orbital electrons. If a-particles strike the atomic nucleus, there appears the nuclear reaction with the release of particles (neutrons, a-particles and others). The interaction of B-particles with the material leads to ionization, the excitation of atomic nuclei and decelerating radiation (as a result of inelastic and elastic collisions with orbital electrons). Bragg curve. The charged particles penetrate more deeply materials, which increases the number of interactions with atoms and molecules. The speed of particles diminishes. Consequently, the probability of new interactions and the frequency of ionizations increase. With the augmentation of the path, the particle ionization increases in a substance and culminates (Bragg peak), and then quickly decreases down to zero (Fig. 1.1). The material - neutrons interaction The material - neutrons interaction depends on the neutron energy. . Slow neutrons: a) ultracold — 10-7 eV; b) cold — up to 5x 10° eV; c) thermal — to 0.5 eV; d) super-thermal — to 10 eV. . Resonance neutrons — 0.5 keV. . Intermediate neutrons — 0.2 MeV. . Fast neutrons — up to 20 MeV. . Very fast neutrons — up to 300 MeV. . Ultrafast (relativistic) neutrons — over 300 MeV. DUAWNThe tissue depth, cm. The absorbed dose, % of the exposition dose 306 9 12 15 18 24 Bragg curve for protons; — the place of maximal ionizations inside of tissue (proton's energy — 160 MeV); — the place of maxima} ionizations inside of tissue (proton's energy — 190 MeV); Slow neutrons are captured by nuclei, as a result there can be induced ra- dioactivity, for example: 2 1560 {Cot pn Co Resonance neutrons are captured only by heavy nuclei. For intermediate and fast neutrons elastic collisions and nuclear reactions are typical. For fast neutrons both inelastic and elastic collisions are characteristic, As a result, protons, a-particles, neutrons and other particles capable of ion- izing are irradiated (indirect ionization by neutrons). Dosimetry of ionising radiation exposure Dosimetry is the quantification and evaluation of ionizing radiations. The tasks of clinical dosimetry: 1) revealing radiation sources, identification of radiation types, activity and energy; 2) determining the radiation influence degree on the object being irradi- ated. 16Dose of ionizing radiation A dose of ionizing radiations is the energy transferred from radiation to the elementary volume or mass of the material being exposed. An exposure radiation dose (photonic: X-ray and gamma radiations — ERD is a quantitative characteristic of radiation based on its ability to ionize the air, As @ unit of an exposure radiation dose in the SI system there is accepted sucha dose which in 1 kg of dry air generates ions with the charge of 1 Coulomb of a single sign — C/kg. The off-system unit of an exposure radiation dose is a Roentgen (R). At radiating with an exposure radiation dose equal to 1R in 1 cm? of dry air under normal physical conditions there are formed 2.08x 10° pairs of ions. The deriva- tive of Roentgen: 0.001 R= 1 mR; 0.000001 R= 1 mkR. Exposure radiation dose power of photonic radiation (PERD) is an exposure radiation dose per a time unit — 1 C/kg x sec = 1 A/kg. The off-sytem unit — R/hour, mR/sec. An absorbed ionizing radiation dose (D) is the energy transferred from ra- SP ciation to.a mass unit of the material being exposed. In the Si system Grey (Gy) is 1 J/kg. The off-system unit of an absorbed dose is rad (from “radiation ad- Wsorbed dose”). Ns 1Gy=100 rad, 1rad =0.01Gy Absorbed ionizing radiation dose power is absorbed ionizing radiation dose pera time unit (Gy/sec, rad/sec). An integral absorbed radiation dose is the average energy transferred to a certain mass of the exposed tissues, organ, part or the whole body, — Gy x kg (rad xkg). An equivalent radiation dose (H) — Sievert (Sv) is such an absorbed ioniz- ing radiation dose (of any type) which causes the same biological effect as 1 Gy of an absorbed ionizing radiation dose of X-ray or gamma radiations (J/kg); 0.01 Sv=1rem (the biological equivalent of roentgen). A personal equivalent radiation exposure dose is the sum of equivalent radiation doses which a human absorbs during life-time. A collective equivalent radiation exposure dose is equal to a personal ef- fective radiation accumulated doses of a population group for a definite time interval. The measurement unit — person-Sivert (person-Sv). A population dose is equal to all the effective radiation accumulated doses of the country’ aL TESSOUESES Ol Fadiation exposure. The mea- surement unit > levers) «Hi MEQMYHMG | YHTBEPCHTET YAUM, | 9 lnesrvebiaynanne xon 16476 BIBMIOTEKAn equivalent radiation dose (H,,,) in an organ or tissue is the magnitude which is defined as a result of mutiplication of an absorbed dose in a separate organ or tissue by the radiation suspended factor (WR). H, =DxWR The radiation suspended factor is the coefficient which takes into ac- count the biological efficiency of different types of ionizin 9 radiations in the association with different magnitude of the linear transmission of energy (LTE). LTE is the ratio of a complete energy (dE) which is transferred to the material by a charged particle as a result of collisions on the way (dL), and the path length. dé LTE =— dl The value of the radiation suspended factors (SR) (see Table 1.2) Table 1.2. The value of the radiation suspended factors (SR) Types of radiation WR Photons: X-rays and gamma-rays, all energies 1 Beta-particles, muons, all energies 1 Protons (<10 MeV) 10 Neutrons (2-10 MeV) 10 Alpha-particles, heavy nuclei of recoil 20 Distribution of doses in some organs and tissues depends on the magni- tudes of equivalent doses and the value of tissues suspended factors for sepa- rate tissues or organs. The tissue suspended factor (Wt) is the coefficient which reflects the rela- tive stochastic (probable) risk of irradiating a separate tissue or organ to the total risk at the uneven radiation exposure of the body (see Table 1.3) An effective dose of radiation exposure (E) is a sum of equivalent doses of works (H,) in separate organs and tissues multiplied by the corresponding tis- sues suspended factors (Wt). The unit of measurement is Sivert (Sv). E=SH,xW,Table 1.3. The value of tissues suspended factors Ne Atissue or organ wr | Ne A tissue or organ wt i Gonades 0.20 | 8 The liver 0.05 2 The red marrow 012 | 9 The esophagus 0.05 3 The colon 0.12 | 10 The thyroid 0.05 4 The lungs 012 | 11 The skin 0.01 s The stomach 012 | 12 A bone surface 0.01 6 The urinary ladder 13 Other organs 0.05 7 The mammary gland 0.05 | 14 An effective dose allows defining probable total risk from radiation exposure of different areas of the body in different absorbed doses. The value of effective doses is summed up for each person during a life-time and this total magnitude is adopted as the index of the accumulated risk of radiation exposure. A collective effective dose (S) is the sum of personal effective doses of ra- diation exposure of a certain population group for a certain interval of time or the sum of average group effective doses works multiplied by the number of persons in corresponding groups which form the collective for which it is calcu- lated. The measurement unit — person-Sivert (person-Sv). Apopulation dose is the total effective dose of irradiating a country's popula- tion from all sources of radiation exposure. The measurement unit — Sivert (Sv). A power of radiation exposure effective dose is an effective dose per a time unit — 1 SV/s; 0.01 Sv/s = 1 rem/s. The effective period of half-decay and half-excretion of a radionuclide (T,,,) is the time during which the number of radionuclides in an organism diminishes twice as a result of its radioactive disintegration and biological excretion. Methods of Dosimetry They distinguish the following methods of dosimetry: physical (ioniza- tion, luminescent, semiconductive, thermoluminiscent, neutron-activating, calorimetrical, photographic), chemical, biological and calculative (mathe- matical). 19The ionization method of dosimetry is used with an ionization chamber and based on estimating the degree of ionization of the environment through which radiation passes. The greater the power of the dose, the more ions ap- pear, the greater is the ionization current. Measuring the size of the ionization current gets the picture of the power of an ionizing radiation dose. The scintillation method of dosimetry consists in measuring the intensity of light flashes which emerge in materials with the luminescent property (po- tassium iodide, sodium, caesium or anthracene, stilbene and others) during the passage of X-rays or y-rays through them. The semiconductive method of dosimetry — during radiation exposure in semiconductive detectors there emerges the current after the magnitude of which it is possible to define the radiation dose power which affects a detec- tor. The thermoscintillation (photoscintillation, radioscintillation) method is based on the ability of a crystalline luminophore (lithium fluoride activated by silver) to accumulate absorbed radiation energy. In case of additional heating of crystals in a certain mode there occurs a thermoscintillation “flash” the in- tensity of which depends on the dose of radiation exposure which the lumino- phore has absorbed The neutron-activating method is the determination of directed radioac- tivity as a result of neutrons streams influence. The photographic method of dosimetry is based on the ability of radia- tion to cause the photolysis of haloid silver (see above) as a result of which there occurs its partial recreation. In the process of revealing in places of radiation exposure the film darkens proportionally to a dose of radiation exposure. The chemical method is based on the ability of ionizing radiations to cause in compounds the dissociation of polyatomic molecules with the formation of new compounds. The transparency or colour of solutions changes, some part of a dissociation product sediments or turns into gas. The quantitative estima- tion of these changes allows defining a dose of radiation exposure using the measuring system graduated with the use of a standard radiant. The calorimetrical (thermal) method of dosimetry — is based on measur- ing the amount of heat which is excreted in a detector at absorbing ionizing radiations (little used in medicine because of its low sensitiveness). The calculation (mathematical) method — supposes using tables and no- mograms for calculating personal absorbed doses at different variants of irra- diating a person. 20The biological methods of dosimetry are based on evaluating biomate- rials (chromosomal analysis of lymphocytes of peripheral blood, the marrow biopsy phantom, the electronic paramagnetic resonance of the teeth enamel extracted after medical indications) and the account of radiation reaction of the organism. This method of dosimetry is used in clinical practice. Geiger detector + id. ‘ : | F; intensifier detector display — ¢ high-voltage ‘source Fig. 1.2. The principle scheme of a radiometer Types of devices for measuring of a dose and radioactivity Dosimeters are personal searching dosimeters of defence control, labora- tory and clinical (VJ-18, VJ-23). They are used for the determination of dose rate. Radiometers are used for the determination of a sample activity of the external environment objects and levels of radioactive contamination of sur- faces and in vitro diagnostics (Fig. 1.2). There are laboratory radiometers for the determination of activity of 3°Cs and “°K, of 26Ra and 27Th; well-type detectors, spectrometers, spec- trometers of the radiation of a man — WBC (whole body counter), WBRM (whole-body radiation meter) and clinical radiometers (radiometers, ra- diographs, scanners, scintillation gamma chambers, single-photon emis- sion computed tomography — SPECT, positron emission tomography — PET). THE NORMS OF RADIATION SAFETY OF UKRAINE (NRSU-97, NRSU-97/D-2000) These are the basic state documents which set the hygienic norms of radio- logical defence of people. 21The radiological defence of population is based on the following principles of radiation safety: 1) the principle of justification — the practical activity which is accompa- nied by irradiating people must not be carried out, if the benefit from it does not exceed the harm which it inflicts to the man or society; 2) the principle of not exceeding — the levels of the radiation exposure cumulative effective doses as a result of the industrial activity must not exceed the established limits of doses (see Table 1.4); 3) the principle of optimization — personal doses and the number of persons exposed to rays must be as minimal as possible taking into ac- count social and economic factors. By the NRSU-97 there have been set the following categories of persons exposed to radiation. 1. Category A (personnel) are the persons who work directly with sources of ionizing radiations. 2. Category B (personnel) are the persons who do not work directly with sources of ionizing radiations, but in accordance with the location of their workplaces in premises with radiation-nuclear technologies can get an additional radiation exposure. 3. Category C is the entire population of a country. Table 1.4. Limits of radiation exposure doses (mSv/year) Limits (quotas) of doses A category of persons (individuals) exposed to radiation A B c LO, (limit of an effective dose) Limits of an equivalent dose 20 2 1 of the external radiation exposure LD, (for the lens of an eye) 150 15 15 LO, (for the skin) 500 50 50 LO sam (for hands and feet) 500 50 - Note: a) the distribution of a radiation dose during a calendar year is not regu- lated; 22b) proper limitations are valid for women of childbearing age (under 45 years) and expectant mothers. NRSU-97 includes 4 groups of radiation-hygienic regulated values. The first group of regulations is set for taking control over practical activity for the limitation of the professional radiation exposure in conditions of nor- mal exploitation of industrial sources of ionizing radiations. These are limits of doses, derivative levels, acceptable levels (AL) and control levels. The numerical values of doses limits (Table 1.4) are set at the levels which exclude any possibility of the emergence of Deterministic effects of radiation exposure from the influence of a sum of the effective doses of all sources. The second group of regulations is set for the limitation of medical radia- tion exposure of persons in medical practice. This group includes recommend- ed maximum levels. During performing X-ray and nuclear imaging they distin- guish the following categories of patients. Category AD: patients with oncological diseases or with the suspicion of them; patients whose evaluation is conducted with the purpose of differen- tial diagnosis of innate cardiovascular pathology, including vascular peripheral malformations; patients for whom intervention measures are taken; persons being explored in emergency practice (including traumas) after vital indica- tions. The maximum permissible radiation exposure dose (ADL — Administra- tive Dose Limit) is 100 mSv/year. Category BD: patients, for whom evaluations are conducted after clinical indicators at somatic (non-oncologic) diseases with the purpose of clarifying the diagnosis and (or) the choice of the treatment tactic. ADL — 20 mSv/year. Category CD: persons from risk groups who work at enterprises with harm- ful pathogenic factors and those who are admitted to work at those enterprises and who pass a professional selection; patients struck off the medical record after radical treatment for oncologic diseases at periodic examinations. ADL — 2 mSv/year. Category DD: persons for whom all types of prophylactic inspection are conducted, except for those belonging to category CD; persons for whom examinations after medical programs are conducted, ADL — 1 mSv/year. The third group are regulations concerning the dose of radiation exposure of population prevented as a result of interference in conditions of a radiation failure. This group includes interference levels and effect levels. The fourth group are regulations concerning the dose of radiation exposure of population from technogenic strengthened sources prevented as a result of 23natural origin interference (sources of natural origin ionizing radiation which as a result of human economic and production activity were concentrated or their availability was increased, which, in tur, led to the formation of radiation exposure additional to the natural radiation background). This group includes interference levels and effect levels. ADL in emergency situations When emergency works are carried out for the rescue of people's lives, the radiation exposure doses of the emergency personnel must not exceed the values regulated by NRSU-97: the equivalent dose of any organ (together with the even radiation exposure of the whole body) must not exceed 500 mSv. The planned increase of the personnel radiation exposure doses over 100 mSv is accepted with the permission of the Ministry of Health of Ukraine — one time during all the labour activity. In European and other countries of the world the lonizing Radiation Regula- tion (IRR) are used (see Table 1.5). lonizing Radiation, Protection and Regulation: Revised legislation: The Radioactive Material (Road Transport) Regulations 2002. Inclusion of Best Practicable Means, required by the Environment Agency under Radioactive Substances Act 1993. New Legislation: High Activity Sealed Radioactive Sources and Orphan Sourses Regulations 2005. Section on Protection of Patients rewritten to follow ionizing radiation (Medical Exposure) Regulations 2000, Schedule 1, employer's Procedures. Table 1.5. Annual dose limits in the lonizing Radiations Regulations 1999 (IRR 1999) Limits of doses under 18 years | over 18 years | Others Dose limits for the whole body (mSv) 20 6 1 Dose limits for some organs 500 150 50 and tissues (mSv) Dose limits for the lens of an eye (mSv) 150 15 15 24CONTROL TASKS Questions for self-control 1, The history of discovery of radioactivity. . Nature and properties of ionizing radiations, . Radioactivity, units of radioactivity. . Dosimetry. Types of dosimeters. . Chemical methods of dosimetry. . Limits of radiation exposure doses. 2: 3. 4, \sotopes. The basic descriptions of radioactive isotopes. 5. 6. 7. 25GSR 0 BIOLOGICAL EFFECTS OF IONIZING RADIATIONS THE STAGES OF A RADIATION DEFECT Under the biological effect of ionizing radiations they understand their ability to cause functional, anatomic and metabolic changes at all levels of bio- logical organization. The biological effect of ionizing radiations is predefined by the energy which is passed by radiations over to different tissues and or- gans. At the basis of the biological effect of ionizing radiations there lie: + absorption of radiation energy by a biosubstrate; + ionization and excitation of atoms and molecules, radiolysis of water with the formation of free radicals H* OH” and hydrogen peroxide — H,0. + formation of active free radicals and development of primary radia- tion-chemical reactions and damage of high molecular compounds. The primary effect of radiation can be linear and non-linear. There are the excitation and ionization of molecules, tissues and organs at direct radiation influence (see Table 2.1), lonization and excitation of the tissue atoms and molecules exposed to rays is the primary physical process, the starting mechanism of the biological ef- fect of ionizing radiation, that is why it is called the direct effect. Thus there is a disruption of molecular associations with the formation of free radicals with high chemical activity. They interact with surrounding intact atoms and molecules (molecules of organic materials dissolved in water: proteins, nu- cleoprotein, lipids, enzymes and others), as a result of which there occurs their splitting with the formation of following free radicals which interact with the molecules unexposed to rays and predetermine the indirect effect of ionizing radiation, that is changes of molecules emerge not from the got energy of ion- izing radiation, but from the energy of the changed molecules (during radia- tion exposure a very insignificant part of molecules of the organism exposed to rays find themselves under the direct effect). 26Table 2.1. The stages of radiation defect Time A stage of defect Alevel of biologi- cal organization 10? sec | Physical interaction, absorption of energy, ionization} Molecular and excitation of molecules 107-10? sec | Primary radiochemical reactions, formation of radi- | __Subcellular cals. Changes in molecules, violation of biochemis- try of cells Seconds — Damages of cells: violation of structures which Cellular minutes provide functioning and heredity of cells Minutes — | Violation of morphology of cells andtheir death | — Tissue, organ hours Minutes — | Damages of the whole organism: violation of func- The whole months tions of organs and systems; morphological changes organism in organs and systems; death of the organism During one's | Remote somatic effects (decrease in body resis- lifetime tance, reduction in lifetime, development of cancer or leukosis, dystrophic changes of tissues) indefinitely Genetic consequences of radiation exposure Population long time The basic biosubstance of oxidizing reactions caused by free radicals are biolipids and nucleoproteides. As a result of radiation influence the structure of tissues and cells is damaged. lonization of atoms and molecules leads to the change in the molecular structure, which results in violation of biochemical processes in organs and tis- sues and displays in disorders of tissue breathing, change in enzyme system's action, violation of protein synthesis, etc. lonizing radiation always has a destructive effect on a living organism. The reactions of an organism to radiation exposures are variable and de- termined by both the nature of radiation and condition of the organism itself. The degree of radiation defects correlates distinctly with the partial pressure of oxygen in tissues — the less is the partial pressure of oxygen, the less is the radiation defect (the so-called “oxygen effect’). In the conditions of hypoxia, the radiosensitivity of the organism can decrease in 2-3 times. 27FEATURES OF THE BIOLOGICAL EFFECT OF IONIZING RADIATIONS 1. The biological effect depends upon an absorbed dose and power of a radiations dose (linear dependence) — the effect increases with the growth of the dose and its power. Pathological changes emerge at all levels of organism integration — molecular, cellular, organ, and in an organism as a whole. The effect of radiation exposure is related to the distribution of a dose in time, that is to the speed of the energy absorption. The disintegration of the same total dose into separate fragments leads to the diminishing of a radiation defect degree. The processes of renewal begin at once after radiation exposure and are able to compensate, at least partly, the caused violations. . The degree and form of a radiation defect are determined by radiation energy distribution in the organism. The greater destruction is caused by the radiation exposure of the whole organism which is the general radiation exposure. The lesser changes are caused by the influence of the same dose on separate parts of the organism which is called the lo- cal radiation exposure. It is important which parts of the organism are exposed to rays. The greatest consequences are caused by the radiation exposure of the stomach, and the least — by the radiation exposure of the extremities. 4. The biological effect depends upon the type of radiation (see the sec- tion “The material - ionizing radiation interaction”). Consequently, all types of ionizing radiations, either themselves or indirect- w ly, cause excitation or ionization of atoms or molecules of a biological system. However, at the radiation exposure of objects by different types of ionizing radiations in even doses there emerge quantitavely, and sometimes qualita- tively, various biological effects. That is why there was introduced the concept of the relative biological efficiency (RBE) of ionizing radiations (see the section “The material — ionizing radiation interaction”), 28 5. The presence of the latent period of the radiation effect. The latent pe- riod is the interval of time which covers the period from the moment of radiation exposure to the appearance of changes which are registered clinically. The duration of this period is inversely proportional to the dose absorbed. The higher the dose, the shorter the latent period is. It is necessary to bear in mind that the latent period is a conventional, pure-ly clinical concept, because actually the reaction of radiation exposure develops persistently. . Accumulation ability. If one exposes an area of the skin to adose of 1 Gy, no visual changes will be present. If one repeats radiation exposure for a few days successively, erythema will develop. If radiation exposure is given every day for 2-3 months, there comes necrosis. It takes place because small changes accumulate gradually in tissues which are caused by every radiation exposure, which eventually results in great damages 2 In the formation of the biological effect a special role belongs to the func- tion of the systems which integrate an organism — the nervous system, the en- docrine system and the humoral system (which transports throughout the or- ganism toxic products being formed in tissues as a result of radiation exposure). Nervous receptors experience the influence of toxic products, which results in the violation of nervous regulatory processes and the emergence of chain self-accelerating reactions in an organism exposed to rays, predetermines the development of a radiation defect at subsequent stages with the typical peri- odicity of the pathological process development. The following important statements are the derivatives from the aforesaid: 1. The interaction of ionizing radiation with living material takes place af- ter the laws of physics and is accompanied by excitation and ionization of atoms and molecules and primary radiochemical processes (reac- tions). But this is only the primary effect of radiation. . lonization of atoms and molecules is only the starting mechanism for secondary processes which further develop in a living organism after biological laws. That is why the efficiency of the biological effect of ion izing radiations is estimated from the point of view of the severity of these secondary damages. N The effect of ionizing radiations on cells and organisms of warm-blooded animals As a result of radiation exposure in a cell it is possible to register a great number of most various reactions — delay of division, suppression of DNA syn- thesis, damage of membranes and others. The degree of expression of these reactions depends on a stage of a life cycle at which a cell radiation exposure took place. 29Itis known that the synthesis of DNA in a cell takes place in an interphase which is divided into 3 periods — the period of synthesis of DNA (S-peri- od), before — (G,) and postsynthetic (G,) periods, the fourth period — mi- tosis (M). The duration of the mitotic cycle varies in time, being disposed as follows: M < G, < S < G,. The shortest period — mitosis — is over within 30-60 minutes. Some radiation reactions are easily born by a cell, as a result of structures’ damage the loss of which is very quickly restored. The most universal reaction is the temporal delay (suppression) of cellular division that is often named the radiation blocking of mitoses. For the majority of cells cultures the delay of division is equal to approximately 1 hour per every 1 Gy. The duration of the delay time depends also on a stage of a cellular cycle in which cells are at the moment of radiation exposure. It is the longest in those cases when radiation influence is experienced by cells at the stage of DNA synthesis, and the short- est — at radiation exposure in mitosis. One should distinguish the reaction of division from a complete suppression of mitosis, which sets in after the influ- ence of higher doses when a cell continues to live for a considerable time but completely loses the ability to divide. Lethal effects of cells. The forms of cellular death Under cellular death or the lethal effect of radiation exposure one under- stands the loss by a cell the ability to proliferation. Survived cells are those ones which preserved the ability to unlimited reproduction, that is cloning. Thus, the question is about reproductive death of a cell. This form of radio-inactivation of cells is most widespread in nature. Another type of the reproductive death of the exposed cells descendants is the formation of the so-called giant cells which emerge as a result of the con- fluence of two adjacent, “sisterly” cells. Such cells are able to divide 2-3 times, after which they perish. The principal reason for reproductive cell death is structural interaction of DNA as the so-called chromosomal alterations or aberrations. The basic types of aberrations are: fragmentation of chromosomes, forming of chromosomal bridges, dicentrics, circular chromosomes, appearance of intra- and interchro- mosomal exchanges and others. Some aberrations, for example bridges, mechanically hinder the division of cells. The exchange inside chromosomes and between them results in the un- even division of chromosomes, the loss of the genetic material that causes the 30death of a cell as a result of deficit of metabolites, the synthesis of which was encoded by the DNA of the lost part of a chromosome. Still another form of radiation of cells inactivation — interphase death — occurs when cells enter mitosis, At radiation exposure doses of 10 Gy death can occur “under a ray” or soon after the radiation exposure, At a radiation exposure dose up to 10 Gy death occurs within the first hours after radiation exposure and can be registered as varied degenerative changes of cells — more frequently pyknosis or fragmentation of chromatin. The nature of cells' radiation death The sensitiveness of a cell nucleus is approximately six orders higher than that of cytoplasm. Of all intranuclear structures, DNA is accountable for the vi- ability of a cell. The latter takes part in forming chromosomes and the transfer of genetic information. Radiation exposure causes varied interaction in DNA: breaks of a DNA molecule, the formation of alkali-labile associations, the loss of bases and change of their composition, changes of nucleotides sequences, fu- sion of DNA ~ DNA and DNA ~ protein, violations of DNA complexes with other molecules. One distinguishes single breaks of DNA when associations between sepa- rate atomic groups are violated in one of the filaments of a double spiral mol- ecule of DNA and double when a break takes place at once near closely locat- ed areas of two chains, that results in the disintegration of a molecule. At any break, reading information from a molecule of DNA and the spatial structure of chromatin are violated. Single breaks do not result in breakages of a molecule of DNA, because the torn filament is firmly kept in place by hydrogen, hydrophobic and other types of interaction and the opposite filament of DNA. In addition, the structure is re- stored well enough by the powerful system of reparation. Single breaks them- selves are not the reasons for cells destruction. With the increase of a radiation exposure dose the probability of transi- tion of single breaks into double ones grows as well. Rarely ionizing radia- tions (gamma, X-ray, fast electrons) per 20-100 single breaks cause one double break. Densely ionizing radiations cause a much greater number of double breaks of DNA and chromosomal aberrations immediately after radiation exposure. Alongside the formation of breaks, the structure of bases in the exposed DNA, foremost of thymine, is violated, that increases the number of genes mu- atations. The formation of fusions between DNA and proteins of a nucleoprotein complex is marked, Finally, the important consequence of radiation exposure is the change of epigenomic (unconnected with the nuclear material) heredity of a cell the transmitters of which are varied cytoplasmic organels, Thus, the functional ac- tivity of the exposed cells descendants decreases, Probably, exactly it can be one of the reasons for remote consequences of radiation exposure. However, the main reason of reproductive cell death at radiation exposure is the dam- age of their genetic apparatus. The post-radiation renewal (reparation) of cells A lot of radiation damages restore. Such damages are named potential. Their fate may be related to two ways: they are repaired and then a cell sur- vives, or realized and then a cell perishes. After the time of realization one distinguishes prereplicative, postreplica- tive and replicative reparations. Prereplicative reparation (before the stage of DNA doubling) can take place by the reunion of breaks and also with the help of exclusion (excision) of the damaged bases. In the uniting of single breaks there take part the enzymes: ligase, endo-, exonuclease, DNA ligase, which provide the eventual act of repa- ration — the ligase reunion. Postreplicative reparation is the process at which a cell keeps its viability, in spite of the presence of DNA defects. Replicative reparation (DNA renewal in the process of its reparation) is car- ried out by eliminating damages in the area of chain growth point, or by elon- gation, passing the damage. They estimate the biological effect of radiations also after radiosensitivity (the appearance of physiological reactions after radiation exposure) and radio- lethality (radiolethality: ML 50/30 causes the death of 50 % animals during 30 days; ML 100/30 — causes the death of 100 % exposed to rays), A radiation defect depends on personal sensitiveness to ionizing radiation and general reactivity of an organism during radiation exposure. There are spe- cific differences in sensitiveness in mammals. A mortal dose for a man is more than 6 Gy, for a dog — 6 Gy, for a guinea-pig — 5 Gy, for a rat — 8 Gy, for a bird — 8-10 Gy, for a rabbit — 12 Gy, for the simplest (amoeba) — 1000 Gy, for bacteria — hundreds of thousands ‘of Gy (Micrococcus radiodurens lives and reproduces itself in channels of functioning atomic reactors), 32Radiosensitivity depends on age (in children it is considerably higher than in adults and elderly persons), genetic constitution, state of health (patients are usually more radiosensitive than healthy persons), nourishment (the valu- able and balanced nourishment promotes radioresistance), hormonal status (the hormonal status violation promotes radiosensitivity), gender (females are more radioresistant than males), the amount of oxygen in the atmosphere during irradiating biological objects (the oxygen effect is an increase of radio- sensitivity at the growth or decline of the oxygen partial pressure in the atmo- sphere), the temperature (a decrease in body temperature below normal lev- els is accompanied by an increase of radioresistance). In 1906 |. Bergonie and L. Tribondeau noted that the radiosensitivity of tissues is directly proportional to the proliferative activity and inversely pro- portional to the degree of differentiation of the cells constituting it. That is why haemopoetic tissue, lymphoid tissue, the gonades, the lens of an eye and others are most sensitive. This concerns muscular tissue first of all. Depending on radiosensitivity, 3 groups of critical organs or tissues are establishe Group | — the whole body, gonades and the red marrow, lymphoid tissue. Group Il — the thyroid, fatty tissue, the liver, the kidney, the spleen, GIT, lungs, muscles, lens of an eye and organs which do not belong to groups | and Ill. Group III — the skin, bone tissue, hands, forearms, shins and feet. The mechanism of tumor cells' radiation damage Radiotherapy is based on the biological effect of ionizing radiations (see Section 1). As a result of the radio influence there is the oppression of cellular division in a tumor. The doses like 0.1 Gy cause the disappearance of normal mitotical numbers. With increase in dose still more cells lose the ability to re- production. The number of abnormal mitoses of the tumor cells grows, and the cells which continue to reproduce themselves after some divisions perish as a result of the harmful influence of chromosomal aberration and genes muta- tions related to the damage of DNA. There appear endophlebitis and prolifera- tive endarteritis in blood vessels of the tumor. The obliteration of tiny vessels violates tumor feeding, which strengthens dystrophic changes in it and con- tributes to tumor death with substituting it by connective tissue. Specialists in radiotherapy aspire to the most complete destruction of tumors elements at the least damage of surrounding healthy tissues. It becomes possible because 33in the whole organism at the same absorbed dose the damage of tumor tissue usually occurs quicker and is expressed to a greater degree as a result of low differentiation of tumor cells and their higher radiosensitivity (the appearance of the physiological reaction after radiation exposure) in comparison with sur- rounding normal cells, the nervous system activity and the presence of the an- tiblastic defence of healthy tissues factors. The difference in normal and tumor cell radiosensitivity is named the therapeutic interval of radiosensitivity. The greater this interval is, the eas- ier it is to obtain tumor destruction at saving the viability of surrounding tis- sues. The radiotherapeutic interval can be extended by changing radiation exposure rhythm: a set total dose of radiation exposure is divided into sepa- rate parts (fractions). A tumor is exposed to rays repeatedly, by small (2-3 Gy), middle (5-6 Gy) or large (8-12 Gy) fractions. Another way of increasing the ra- diotherapeutic interval is dose protraction. In these cases each fractioned ra- diation exposure is prolonged by decreasing the power of a dose. Radiomodi- fiers — radiosensibilizators and radioprotectors — are also used. Expansion of the radiotherapeutic interval is promoted by: radiosensibili- zators (increase tumors radiosensitivity); satiating a tumor with oxygen (radia- tion exposure in the conditions of oxygenotherapy); synchronization of cells division cycles; hyperthermia and magnetotherapy. Some chemical means strengthen a radiation defect (the primary damage of DNA) — fluorouracil, methotrexate, heparin; weaken the postradiation renewal of tumor cells — the antibiotics of the actinomycin group — actinomycin D, aurentine and others; worsen tumors’ trophic conditions — gexamine and others. Radioprotectors — reduce the sensitiveness of normal tissues to radiation exposure. These are pharmaceutical preparations (serotonine, cystamine, cys- teine and others) hypothermia and hypoxia (inhalation of a mixture of nitro- gen with oxygen containing up to 12 % of oxygen, putting a tourniquet on an extremity). With the purpose of strengthening the radiation damage of cells, the so- called radiosensibilizators are used. Here belong chemical remedies which strengthen the primary radiation defect by the increase of satiation of tumor cells with oxygen (heparin), that strengthens the primary damage of DNA. They also strengthen the radiation defect — (fluorouracil, methotrexate), loosen the postradiation renewal of tumor cells (the antibiotics of the actinomycin group — actinomycin D, aurentine and others), worsen the conditios of tumor trophic (mexamine and others). 34In 1938 B. Ye. Peterson on the basis of the study of tumors radiosensitivity, developed the classification of radiosensitivity which in our days is acknowl. edged by many scientists: 1) radiosensitive tumors — seminoma, thymoma, lymphosarcoma, Ewing's tumor, basalioma and others; 2) moderately radiosensitive — epithelial carcinoma; 3) moderately radioresistant — adenocarcinoma; 4) radioresistant tumors — neurofibrosarcoma, fibrosarcomas, teratomas, skin melanomas, chondrosarcomas and others. The radiosensitivity of tumors depends on their histological structure, the degree of differentiation of cellular elements, the correlation of stroma and pa- renchyma (tumors rich in stroma are less sensitive to radiation as a result of poor oxygenation), blood supply, localization, the size of a tumor (tiny tumors are more sensitive than large ones), the speed and character of growth: endo- phytic carcinomas are more sensible than exophytic ones. Success of radiotherapy of malignant tumors depends on a method of radia- tion exposure and a dose. There is an optimal dose within 60 to 120 Gy depend- ing on the histological structure, localization of a tumor and other factors, Very high doses can affect healthy tissues around a tumor, violate vasculari- sation, which causes tumor tissues anoxia and increases their radioresistance, Consequently, very high doses can be harmful, and small ones are simply not effective. That is why the choice of an optimal effective dose depends on the morphological structure of a tumor, a stage of disease, the state of surrounding normal tissues, the general condition of a patient and the other factors listed above. Principles of the defence from the ionizing radiation effect 1. The defence by amount — the diminishing of the sources power up to minimal values at a workplace. The dose and activity are in inversely proportional dependence (the less the activity of radiation exposure source, the less the dose of radiation exposure is). 2. The defence by time — the reduction of the time of the contact with a radiant. The time and dose are in inversely proportional dependence (the less the time of the contact with a source of radiation exposure, the less a dose of radiation exposure is). 353. The defence by distance — the increase of the distance between aman and a radiant. The distance and dose are in inversely proportion- al dependence (the greater the distance from the source of radiation exposure, the less the dose of radiation exposure is). 4, The defence by a screen — screening sources with materials which ab- sorb ionizing radiations. Protective means against ionizing radiation effect 1. Personal: clothes, special footwear, protective means for respiratory or- gans, insulating suits, additional protective devices. 2. Collective: walls, pressurized production equipment, ventilation and others. Radioactive wastes Radioactive wastes (RAW) are material objects and substances whose ra- dioactive contamination exceeds the levels set by valid norms under the condi- tion that the use of these objects and substances is not supposed. Depending on their physical state RAW are divided into solid, liquid and gaseous. Collection of RAW is carried out in the establishments where their forma- tion took place. Solid and liquid RAW are kept in special containers-collectors. The uncontrolled pouring liquid RAW out into the domestic sewage system and into the environment is forbidden. Pouring liquid RAW out into the domes- tic sewage system at the simultaneous observance of the BSRU-2001 require- ments is accepted. If the contents of some radionuclides in wastes exceeds the concentration possible for pouring out into the sewage system, they are col- lected in special containers and transported, as well as solid RAW, by a specially equipped transport to specialized organizations for processing and burying RAW. The deactivation of radioactive wastes The deactivation of radioactive wastes can be executed by the following methods: 1) to keep until a complete disintegration (10 half-decay periods); 2) to dissolve with water or air up to the maximally accepted concentration; 363) to bury radioactive wastes in special grave-diggers (highly active long- living). CONTROL TASKS Questions for self-control Methods and facilities of protection during work with ionizing radiation. The biological action of ionizing radiation. The direct and indirect action of ionizing radiation. Specific, individual and age varieties of radiosensitivity. The mutagenic action of radiation. . The influence of external conditions on organism's radiosensitivity. . Categories of patients directed for X-ray examination. Possible doses of ra- diation. Categories of persons and the threshold doses according to IRR-99. The deactivation of radioactive wastes. NOAM bok ad 37raeeraer Tr Radiotherapy Chapter 3. Principles and Fundamentals of Radiation Therapy of Malignant Tumors and Non-Neoplastic Lesions. Chapter 4. X-ray Therapy. Chapter 5. Long-Focus Radiotherapy. Chapter 6. Brachytherapy.OF RADIATION THERAPY OF MALIGNANT TUMORS AND NON-NEOPLASTIC LESIONS Radiotherapy is a section of Medical Radiology which studies the applica- tion of ionizing radiations for the treatment of malignant tumors and non-neo- plastic lesions. Radiotherapy of malignant tumors and non-neoplastic lesions is conducted at radiological departments of oncological dispensaries and research insti- tutes. CLASSIFICATION OF RADIOTHERAPY METHODS Since 1970's this section of Medical Radiology has been divided into two constituents: Radiotherapy and Radiosurgery. The classification of radiotherapy methods: 1. Long-focus (source-skin distance /SSD/ is within the interval of 30 cm to2m) + X-ray therapy (superficial, half-deep, deep) * gamma-therapy (static, dynamic) ¢ irradiation with high energy sources (with the application of linear or cyclic accelerators) 2. Close-focus (SSD is within the interval of 1.5 cm to 30 cm) 3. Contact (SSD is 0 cm) + application + interstitial + intracavitary + with incorporated radionuclides 4, Radiosurgery 39THE MAIN PRINCIPLES OF RADIOTHERAPY The main principles of radiotherapy for malignant tumors . The timely application of radiotherapy at the early stages of the disease. 2. The choice of the most rational methods of irradiation. . Holding up an optimal dose at an optimal time to the tumor while sav- ing the viability of surrounding healthy tissues and under the decrease of the total dose absorbed by the organism. Simultaneous radiation influence on the primary tumor and regional metastasizing ways. . The complexness of the patient's treatment; the application, together with radiotherapy, means which increase the general and local reactiv- ity of the organism. w > w The main principles of radiotherapy for non-neoplastic lesions . Radiotherapy for non-neoplastic lesions is only used when well-ground- ed indications for that are present. . Radiotherapy is the method of choice and it is used, as a rule, when a positive effect of already applied medications has not been achieved, and a probability of somatic, genetic and radiation damages is exclud- ed completely. . Radiotherapy for non-neoplastic lesions should not be applied to chil- dren, teenagers and pregnant women. . The main method of irradiation is an immediate influence on the patho- logically changed organs and tissues. . Radiotherapy should be conducted with the application of methods which minimize the irradiation of vitally important organs and tissues. N w B wv THE SOURCES OF IONIZING RADIATIONS APPLIED FOR RADIOTHERAPY Radionuclide sources of ionizing radiations Radionuclide sources of ionizing radiations are sources of an immediate ef- fect radiations containing radioactive substances. 40A closed source of ionizing radiations — is a radionuclide source of ion- izing radiations the construction of which excludes getting of the radioac- tive substance (it contains) to the environment (for example, radioactive needles, beads, gamma therapeutic apparatuses for static and dynamic ir- radiation). An open source of ionizing radiations — is a radionuclide source of ion- izing radiations whose application makes getting of the radioactive sub- stance (it contains) to the environment possible (solutions and suspensions of RP), Non-radionuclide sources of ionizing radiations Non-radionuclide sources of ionizing radiations are technical devices not containing radioactive substances but under certain circumstances are capable of generating ionizing radiations at the expense of accelerat- ing and decelerating charged particles. These are generators of X-radiation (X-ray apparatuses for close-focus and long-focus X-ray therapy), generators of decelerating and high energy corpuscular irradiations (linear accelerators of electrons, betatrons, microtrons, synchrophasotrons, synchrocyclotrons and others). Depending on the spatial location of the radiation source in relation to the patient's body, they perform external irradiation (on the skin's side) and inter- nal irradiation (the radiation source is placed in the patient's body). For radio- therapy they use closed (Co, '’Cs, Cf, Ir, etc.) and open (P, *Sr-chloride, "311, "Au, and others) sources. For external irradiation they use closed sources of radiations (most fre- quently Co) in gamma therapeutic and surgical apparatuses and electrophysi- cal installations (roentgentherapeutic apparatuses, linear accelerators, a cy- berknife and others). A gamma installation consists of a radiation head, a support and a patient positioning table (Fig. 3.1). In the radiation head (Fig. 3.2), in the protective lead case, there is placed the source Co with the activity of 150-250 TBq (depend- ing on the apparatus type), with the half-decay period of 3.5 years. The radia tion beam of rays exit is only possible through the window which is closed with the leaf made of tungsten. A special construction enables to perform static and dynamic irradiation. 4iy Fig. 3.2. The scheme of the radia- tion head of the gamma therapeu- tic apparatus 1 — the ionizing radiation source “Co, 2— the tungsten leaf, Fig. 3.1.The gamma therapeutic apparatus 1 — the radiation head; 2 — the support; 3— the table 3 — the lead case, 4— the aperture TYPES AND METHODS OF RADIOTHERAPY At the basis of the radiation types classification there is laid their division af- ter a type of ionizing radiations: X-ray therapy, gamma-therapy, beta-therapy, megavoltage therapy, proton therapy, neutron therapy. Methods of radiotherapy 1. X-ray therapy is the method of treatment of non-neoplastic lesions in which the source of radiation is an X-tube. They distinguish: + superficial radiotherapy — when the pathological focus is at the depth of up to 1 cm from the skin's surface; * half-deep — when the pathological focus is at the depth of up to 3 cm from the skin's surface; « deep — when the pathological focus is at the depth of up to 5 cm from the skin's surface. Il, Long-focus methods of irradiation: + close-focus methods of irradiation are applied at the source-skin dis- tance (SSD) of 1.5 cm to 30 cm; 42+ long-focus methods of irradiation are applied at the source-skin dis- tance (SSD) of 30 cm to 2m. 2.1, Long-focus gamma-therapy Depending on the dose distribution in the space they distinguish static gamma-therapy (unifield, bifield and multifield irradiations) and dynamic gam- ma-therapy (rotation, pendulum-like, sector, tangent and convergent irradiation). Static distant gamma-therapy is performed with open fields (unifield, by- field and multifield irradiations). Under static irradiation the radiation source during the whole time of treatment remains in a fixed position in relation to the patient. To provide the even dose distribution while irradiating objects of a com- plex form they use special compensators of equivalent materials tissue (water, paraffin and others). For shaping the irradiation field of the needed form they use special de- vices: lattice diaphragms, lead wedge-shaped filters, protective blocks, collima- tors. Dynamic long-focus gamma-therapy. Mobile irradiation is characterized by the relocation of the radiation source in relation to the patient during ir- radiation. There are exist rotation, pendulum-like (sector), tangent (eccentric), rotation-convergent gamma-therapy with managed speed. The advantages of mobile irradiation over static one are the following: a high exactitude of the ray beam centration, a considerable decrease and even distribution of radiation load on the skin, which enables to hold up higher dos- es to the pathological area. 2.2. Therapy by decelerating high energy radiation and fast electrons: a) static; b) dynamic; ©) conform therapy on equipped computer apparatuses with the use of three-dimensional or four-dimension planning (X-ray, CT, MRI-stimu- lators) of intensity-modulated radiation therapy (IMRT). Ill. Close-focus methods of irradiation (brachytherapy) Depending on the location of the focus being irradiated they apply: 1. The intracavitary method. 2. The intrastitial method. 3. The application method. 4. The method of selective accumulation of radionuclides (radionuclide ther- apy — treatment with incorporated radioactive preparations). 43IV. The radiosurgical method Radiosurgery is the term first coined in 1968 by the Swedish radiosurgeon L. Leksell. This term means: “The destruction of the selected brain zone with a single high radiation dose through the skull”. This method is currently not only used in neurosurgery, but also in the treatment of many other neoplasms. In radiosurgery they use: Leksell gamma knife, modified linear accelerators, photon cyberknife. Each of the above mentioned methods of treating malignant tumors can be applied as: * the independent method — long-focus or close-focus therapy; + the united method of radiotherapy — a combination of the long-focus and close-focus methods of irradiation; + the combined method of treating malignant tumors includes radiother- apy and surgical treatment under which preoperative, suboperative and postoperative irradiation can be applied. Preoperative irradiation is aimed at: + the prophylaxy of relapses and metastases of tumors; + the devitalization of the most radiosensitive tumor cells; + the decrease of perifocal inflammation; + stimulation of connective tissue development and incapsulation of tumor cells complexes; + the decrease of the tumor volume, which gives the opportunity to perform surgical intervention. Suboperative irradiation is performed during operative intervention with the aim of: + irradiation of the removed tumor bed; * prevention of implantatory metastases; Postoperative irradiation is performed after surgical intervention with the aim of: + the devitalization of residual tumor cells; + the prophylaxy of relapses and metastases of tumors; # the destruction of regional metastases; * stimulation of connective tissue development and incapsulation of residual cancer cells * the complex method of treating malignant tumors presupposes the ap- plication of radiotherapy methods together with hormonotherapy and chemotherapy in the treatment. 44Depending on the treatment purpose, they distinguish the radical pro- gram of radiotherapy (achieving the complete resorption of the tumor and the patient's recovery), the palliative program of radiotherapy (decelerating the tumor's growth, the patient's lifetime prolongation) and the symptomatic pro- gram of radiotherapy (removing some symptoms, for example, pain, compres- sion syndrome and others). The radical program of radiotherapy supposes the complete destruction of tumorous elements in the zone of the primary focus and is aimed at the full recovery of the patient. They irradiate the primary focus and zones of regional metastasizing. Depending on the tumor's localization and its radiosensitivity they determine the method of radiotherapy, regime of irradiation and a radia- tion dose. The total dose per part of the primary tumor is, as a rule, 60-75 Gy, on the zones of metastazing — 45-50 Gy. The palliative program of radiotherapy is performed for patients with the ad- vanced tumorous process under which it is impossible to achieve a complete and stable recovery. As a result of radiotherapy there comes just tumors' partial regression, intoxication decreases, the pain syndrome disappears and the func- tion of the organ damaged by a tumor is partially restored, which provides the patient's lifetime prolongation. Under palliative radiotherapy they use the total doses of 40-55 Gy. The symptomatic program of radiotherapy is applied for removing the se- verest symptoms of tumor disease (compression of the bile ducts, ureters, large veins, obturation of the esophagus lumen, the pain syndrome, prevention of pathological bones fractures and others). THE DOSES OF RADIATIONS APPLIED FOR TREATING MALIGNANT TUMORS The following concepts are distinguished: * a single focal dose (SFD) — the dose which is held up to the patho- logical area for one session of irradiation; + a total focal dose (TFD) — the dose which is held up to the pathologi- cal area during the whole course of treatment; + asingle skin dose (SSD) — the dose which is held up to the skin field for one session of irradiation; + a total skin (superficial) dose (TSD) — the dose which is held up to the skin field during the whole course of treatment; 45For the treatment of malignant tumors they use such sources of ionizing radiations which convey an optimal therapeutic dose to the necessary depth for the complete destruction of tumors with the maximal preservation of sur- rounding healthy tissues. Depending on the tumor's histological structure, its radiosensitivity (Chap- ter 5), size and depth of location, they apply the following total focal doses (TFD) for a treatment course: + for the destruction of epithelial tumors — TFD 50-70 Gy; + for the destruction of adenocarinomas TFD 70-80 Gy; + for the destruction of sarcomas of muscular and osteogeneous origin and melanomas — TFD 80-90 Gy; To prevent tissues radiation damage, total doses of radiation are divided into some parts — fractions. RADIATION REACTIONS AND RADIATION DAMAGES Radiation reactions are reversible changes in tissues which pass in 2-3 weeks after irradiation without any special treatment. Radiation damages are profound, often irreversible, changes of organs and tissues which need a special treatment. Local radiation reactions Radiation erythema emerges after gamma irradiation on the skin field by tiny fractions: SFD 2 Gy up to TFD 30-35 Gy. Erythema is characterized by the stable reddening of the skin, edema, tenderness, Erythema disappears in 2-4 weeks after ceasing the treatment. Dry radiodermitis appears under gamma irradiation on the skin field by tiny fractions: SFD 2 GY up to TFD 40-50 Gy. Objectively: there are augmented erythema and edema, dermis cell division stops as well as that of the hair fol- licles, there emerges epilation and desquamation of superficial tissues, the epi- dermis exfoliates, the skin becomes dry and pigmented. Exudative (wet) radiodermitis emerges under gamma irradiation on the skin field by tiny fractions up to TFD 50-60 Gy. The epidermis is desquamated, on the edges of the desquamated surface there appears a strip of new epider- mis which gradually, within 2-3 weeks, spreads over up to the centre of the damaged area of the skin. The skin in the damaged area exfoliates for a long 46time, is unevenly pigmented, in remote terms there occurs atrophy of epider- mis and epilation. For the sake of prophylaxis of skin radiation reactions, it is recommended to smear the irradiation fields with indifferent fats. It is strictly forbidden to smear the skin with ointments containing salts of met- als (3, Lassar's Paste and others) for prophylaxis of skin radiation burns (an addi- tional influence on the skin of the characteristic irradiation of ointments’ metal at- ‘oms which appear during a radiotherapy session). Radiation damages Early radiation damages can develop during irradiation or within three months after irradiation under exceeding tolerant levels of tissues irradiation (Table 3.1). Early radiation damages are characteristic of more radiosensitive and well regenerating tissues, that is why such damages are quickly recovered. Radiation skin necrosis is not recovered on its own, it can get malign. For the prophylaxis of skin damages under tiny and medium fractioning they consider the concept of a tolerant skin dose. A tolerant skin dose is the total maximal skin dose of ionizing radiation under the exceeding of which there emerge radia~ tion skin damages. The values of a tolerant skin dose are obligatorily taken into account while making up the plan of the patients radiation treatment. Late radiation damages develop three months (sometimes several years) later after irradiation with doses exceeding tolerant levels of skin irradiation. To late radiation damages belong local (radiation fibrosis, indurative edema, radiation ulcer, radiation cancer; radiation damages of internal organs — ra- diation fibrosis, radiation necrosis, radiation ulcer) and general radiation dam- ages (stable morphological changes in the blood, CNS, esophagus, endocrine glands, chronic radiation disease). Radiation damages of tissues require surgical treatment, hormonotherapy, etc. For that reason, to prevent radiation damages of tissues and organs one has to keep strictly to the methods and standards of radiotherapy. DOSIMETRIC AND TOPOMETRIC PREPARATION Various sources and methods of radiation therapy enable to irradiate with a necessary therapeutic dose pathologic processes that are located at different 47depth. The penetrating capacity of ionizing radiation into the human body de- pends on the type and energy of irradiations. Under long-focus irradiation the type and energy of irradiation are selected to provide the damage of the deep- ly located pathological area with a minimum dose of radiation of Surrounding tissues, The relation of the dose at the given depth to the dose in the skin is called a relative or percentage depth dose. The distribution of energy of different irradiation types is presented in Fig. 3.3. Kp | Gammanayn | Drekng vaiaion rtonsdindon 2200 Eos PE Mev Betcomy B= 12 Mev 0 0 100 5 70 5 x 5 5 5 2 30 Z| oo02s | = 10 0 10 |-{10 g 15 3 50 235 % 15 70) 90 100 20 20 25 wor dowe-asea fioom dow=ssem | 0% dane-asem | 1s donee 425 sox dese” ow doc lace” |sowune-sem” | sow une sen sox due ioom [Som Sor=200m [Gen ioe-rem | Gow denote Fig, 3.3. The distribution of energy of different irradiation types The distribution of energy of different irradiation types presented as curves at each point of which there is the same percent of the skin dose. The lines con- necting points with the same percent of depth doses are called isodose curves. On the manufactured section of the patient's body with the place of the Patho- logical area marked on it, a radiotherapist together with a physicist-dosimetrist design the program of irradiation, determine the volume of the irradiation zone. They choose the type of radiation and method of irradiation, sizes and shape of the irradiation fields, direction of the ray beams and draw them on the topographic-anatomic sketch. The topographic-anatomic sketch is performed nowadays on the transversal CT or MRI section (Fig. 3.4 a) at the level of the tu- mor centre. After the irradiation fields have been drawn, they put perpendicu- lar lines through the appointed fields' centres which cross in the tumor centre (Fig. 3.4 b). They define the percent depth dose in the damage focus of each 48Fig. 3.4. CT of the thoracic cavity at the tumor level (a), the marking of the irradiation fields ‘on the CT-section of the same patient (b) - b irradiation field. The number of irradiation fields is determined considering the account of the irradiated tissues tolerance level (Table 3.1). The value of the radiation dose which is held up to the tumor from each irradiation field is limited by normal tissues' tolerance. A tolerant dose is the threshold dose of ionizing radiation which does not cause irreversible tissue changes. A great experience of radiologists is based on the application of “classical” fractioning with a single dose of 2 Gy of gamma radiation daily per 5 fractions a week. For this regime of fractioning there are established tolerant doses of gamma radiation for various organs and tissues (Table 3.1). Exceeding tolerant doses can lead to normal tissues' damages (vessels, connective tissue), to the decrease of their regeneratory capacity, which can affect negatively the disease state. The specific stages of conform topometric radiation preparation are given using the example of a patient with malignant glioma of the brain. I stage — the analysis of the MRI data (Fig. 3.5 a), CT or SPECT (single-photon emission computed tomography) of images in three dimensions in three mu- tually perpendicular planes for evaluating the localization of the pathological area, its size, volume of peritumoral edema, presence of tumor disintegration or presence of cysts, state of surrounding healthy tissues of the brain; Il stage — taking the contour at the pathological area centre and construct- ing an anatomic-topometric map of irradiation on which soft tissue and bone 49Table 3.1. The irradiation tolerant level for various human organs and tissues An organ, tissue A tolerant dose (Gy) of gamma radiation under “classical” fractioning (SFD 2 Gy 5 times a week) The skin 60-65 Mucous membranes 32 The brain, a small volume (up to 100 cm’) 66 The base of the brain, medulla oblongata 26 The spinal cord, an area with the length of up 57 20cm Abone a1 Muscles in adults 90 The heart, the aorta 43 The single lung 30 The esophagus 60 The stomach 35 The smail intestine as: The large intestine, rectum 52 The liver, a small volume (up to 200 cm?) 50 Kidneys 40-50 The urinary bladder 60 The hematopoietic tissue 9 The spleen 55 Lymph nodes 48 Testicles 3 The vulva 25-30 structures are drawn of the skull, the brain, the tumor itself, the zone of its sub- clinic spreading and critical structures (Fig. 3.5 b); {Il stage — with the help of a planning system (“Gammaplan”, for example) there is performed the calculation of the irradiation fields’ sizes and isodose 50Fig. 3.5. The stages of topometric preparation: 4) the analysis of the patient's MRI image with the brain tumor; ) taking the contour and constructing an anatomic-topometric map of irradiation; )drawing the tumor and the zone ofits clinic spreading; d) the construction of an individual anatomic-topometric map distribution. Modified spatial irradiation being supported by the absence of distinct borders of the pathological area, supposes the including in the target volume practically the whole of the brain from two lateral opposite fields. In this there is performed the calculation of single and total focal doses in the pathologic focus, critical organs, adjacent tissues and on the irradiation fields skin. 51'V stage — the construction of an individual topometric map of irradiating the patient which supposes the confrontation of the MRI (CT or SPECT) im- age and the data of dosimetric and topometric accounts of planning systems (Fig. 3.5 d). Methods of three-dimensional (3D) and four-dimensional (4D) planning are being put into practice. Three-dimensional planning accounts three spa- tial tumor sizes and its connection to adjacent organs, which is found out at CT or MRI (possibly SPECT and PET). Four-dimensional planning accounts ad- ditionally the tumor location in the real time mode, which, for example, is ap- plied in a radiosurgical installation cyberknife. These innovative achievements have enabled to start a new direction of radiotherapy — conform radiotherapy. Conform radiotherapy is the opportunity to form irradiation fields which cor- responds maximally to a tumor's shape, volume and localization. THE BASICS OF MALIGNANT TUMORS AND NON-NEOPLASTIC LESIONS RADIOTHERAPY Experts in radiotherapy are striving to destroy tumorous elements as com- pletely as possible under the least damage of surrounding healthy tissues, It becomes possible as in the whole organism, in the same absorbed dose tumor tissue, damage occurs typically faster and is displayed to a greater degree un- der the low differentiation of tumor cells and their higher radiosensitivity (the emergence of a physiological reaction to irradiation) as compared to surround- ing normal cells, the nervous system activity and the presence of healthy tis- sues antiblastic protection factors. Radiotherapeutic interval is the difference between the degree of damage and the degree of recovery of tumor and healthy tissues under equal doses absorbed by them. To increase the effectiveness of radiotherapy and decrease of the negative impact of ionizing radiation on surrounding healthy tissues, they apply radi modifiers. Radiomodifiers applied for increasing tumor cell radiosensitivity (saturating tumors with oxygen, hyperthermia, magnetotherapy, pharmatheu- tical preparations and hemopreparations — fluorouracil, ftoraful, methotrexat, xeloda, temodal) are called radiosensibilizers. Radiomodifiers decreasing the radiosensitivity of normal tissues are: pharmatheutical preparations (etiol, cys- tamine, serotonin); a decrease of the oxygen partial pressure (hypothermia) is called radioprotectors, 52In 1938, B. Ye, Peterson, on the basis of tumors' radiosensitivity research, developed the radiosensitivity classification: 1. Radiosensitive tumors — lymphosarcoma, lymphogranulomatosis, reticulosarcoma, basal-cell cancer, seminoma, timoma, Ewing's tumor and others. 2. Moderately radiosensitive tumors — planocellular cancer with differ- ent degrees of differentiation. 3. Moderately radioresistant tumors — adenocarcinoma. 4. Radioresistant tumors — neurofibrosarcoma, osteogenic sarcoma, fi- brochondrosarcoma, skin melanoma and others. Tumors radiosensitivity depends on their histologic structure, the degree of cellular elements differentiation, phase of the mitotic cycle (in the phase of mi- toses tumor cells are most radiosensitive), the stroma-parenchyma relationship (tumors rich in stroma are less sensitive to radiation impact as a consequence of their poor oxygenation), blood supply (tumors with sufficient blood supply are more radiosensitive as a consequence of the greater ogygen partial pressure values in them at the account of “the oxygenic effect’, localization, tumor's size (tiny tumors are more sensitive than large ones), speed of growth (cells with high growth rate are more radiosensitive than those with low growth rate, nature of growth (exophytic tumors are more radiosensitive than endophytic types). The success of malignant tumors radiotherapy depends in the irradoiation method and the dose value. There is an optimal dose of radiation within 60 to 120 Gy which is defined de- pending on the histological structure, localization of a tumor and other factors. The application of radiotherapy in non-neoplastic lesions In irradiation of the area damaged by the non-malignant process there oc- curs tissue edema diminishing, improvement in tissues cells function as well as microcirculation. In the first hours after irradiation there emerges the dilatation of capillaries, increase of tissue wall penetrability, augmentation of exudation, migration of blood elements to tissues with their subsequent! disintegration and the formation of biologically active compounds. Lymphatic capillaries dilate, which facilitates enforcement of outflow from the inflammatory focus, there diminishes the intrastitial pressure and pain decreases. There goes up the leukocytes phagocytic activity, acidosis is replaced by alkalosis and pain syn- drome decreases. 53The factors influencing the effectiveness of radiotherapy The significance of tissue irradiation volume It is known that the volume of the irradiated tissue determines the degree of biological response. While defining the dose, rhythm of irradiation and volume of the pathologi- cal area, itis necessary to take into account the stage of the disease, anatomical peculiarities of the area being irradiated and paths of regional lymphatic oul- flow. While defining the volume of the tissues being irradiated, they consider the localization, histological structure, nature of growth, spread of malignant tissue, the general patient's state and other factors influencing the choice of methods and radiotherapy effectiveness. While prescribing radiotherapy, it is necessary to evaluate the risk rate, severity of the cancer process and define which of the factors presents the greatest danger — passivity of therapeutic measures or very active treatment. When choosing a treatment method it is necessary to choose the method of irradiation, at which healthy tissue beyond the irradiated volume would receive the lowest dose. Finally, it is necessary to define exactly the doses received by other areas of the organism under irradia- tion The dependence of the therapeutic effect on the radiation type Biological activity depends on the density of ionization or the number of ion pairs which are formed in a unit of a photon or particle run path; dense- 'y-ionizing radiations cause a greater biological effect than rarely-ionizing as a consequence of a lesser dependence of the damage effect on the oxygen content and a lesser postradiation recovery upon sublethal damages. The significance of irradiation time and fractioning A decrease in the dose power in fractionated irradiation saves the stroma undamaged and facilitates damaging tumor cells. Fractionating and protrac- tion (increasing the irradiation time while decreasing the dose power) enlarges the probability of tumor cells irradiation at the stages sensitive to ionizing irra- diation. At the stage of mitosis the cell is most sensitive to irradiation. A radiotherapy course is the period of radiation treatment during which the patient receives a total focal dose. Making a plan of radiotherapy is performed 54by three experts (a radiotherapist, a medical physicist and a roentgenologist) for each individual patient according to the existing strategy of radiotherapy. THE STRATEGY OF A RADIOTHERAPY COURSE A radiotherapy course is comprised of three periods: preradiation, radia- tion, postradiation. The preradiation period: 1. A detailed examination of a patient (clinical, laboratory, US, X-ray, CT, MRI and other studies). 2. Finding out the histological form of the disease (morphological or his- tological verification). 3. Finding out the indications for radiotherapy. Excluding contraindications for radiotherapy. Choosing the type and method of radiotherapy and additional non- radiation medication measures. 6. Finding out the topographic-anatomic relationship of the tumor and surrounding healthy organs and tissues (topometric preparation of a patient). 7. The choice of the optimal single and total dose of radiation. 8. The choice of the optimal regime of irradiation (single, fractionated, continuous). 9. The technology of irradiation. ws The radiation period: 1. Performing irradiatiion. Treatment of malignant tumors of all localizations is performed according to the Order of the Ministry of Health of Ukraine of 17.09.2007 N° 554 “On the confirmation of giving first medical aid protocols in the speciality “Oncology”. 2. The application of treatment additional methods. 3. Taking care of patients, in case of need — correction in treatment planning. 4. Monitoring possible local radiation reactions. The postradiation period: 1. Following up the patient's state. 2. Evaluating the treatment effectiveness. 553. Monitoring possible local radiation reactions and damages. 4. Dispensary monitoring the patient twice a year, If there is no relapse in 10 years, the patient is excluded out of the oncological list. THE INDICATIONS AND CONTRAINDICATIONS FOR PRESCRIBING RADIOTHERAPY The general indications for prescribing radiotherapy are based ona detailed diagnostics confirmed by the morphological verification and defined stage of the disease. The general indications for radiotherapy of malignant tumors 1. Malignant tumors. 2. Metastatic injuries. 3. Some relapsing benign tumors (for example, the brain tumors). 4, Hemoblastoses: Hodgkin's disease: non-Hodgkin's malignant lympho- mas, multiple myeloma, The contraindications for radiotherapy of malignant tumors The absolute contraindications 56 1, Decompensation of function of the cardiovascular system, liver and kid- ney functions. 2. Decompensated forms of diabetes. 3. An expressed intoxication, rise of body temperature above 38°C. 4. The presence of anemia (Hb <70 g/l), leucopenia (L< 3x10%/1), throm- bocytopenia (Thr < 150x 10°). 5. Cancer cachexia, disintegration of tumors with hemorrhage, multiple remote metastases. 6. Survived myocardial infarction (less than 5-6 months since the coming of IM). 7. Active tuberculosis. 8. The general state according to the Karnofsky scale less than 30 %.9. Psychic diseases (in which no contact with the patient is possible and motor hyperactivity is increased). The relative cotraindications _ The absence of a clear pathomorpholagical analysis. ‘Acute infectious diseases or exacerbation of chronic infectious diseases. . Early radiation reactions emerging during the radiotherapy course (ra- diotherapy is going on after their liquidation). 4. A decrease in peripheric blood indices during radiotherapy down to Hb<70 g/l, L<3x 10%, Thr<150x 10°. With the normalization of these indices the radiotherapy course continuation is possible. Infancy (childhood), pregnancy and lactation period (prescribing radio- therapy is possible in malignant tumors). wn w The indications for X-ray therapy of malignant tumors and non-neoplastic lesions . Skin basal-cell cancer. Diseases of the nervous system — radiculites, neurites, polyneurites, dis- seminated sclerosis, syringomyelia, postamputation pain syndrome, etc. . Inflammatory diseases — carbuncules, furuncules, mastites, hydrade- nites, slowly granulating wounds, steomyelitis, thrombophlebitis, peri- proctitis, etc. Degenerative-dystrophic and metabolic processes — arthroses, spon- dyloses, osteochondroses, ossifying bursites, peritendinites, heel spurs, etc. 5. Skin disease — dermatoses, non-microbial eczema. 6. Postoperative complications: anastomosites, fistulas, causalgia, etc. N w S The contraindications for X-ray therapy of non-neoplastic lesions The absolute contraindications: 1. Apatient's severe state. 2. Decompensated states of the cardiovascular and respiratory systems, liver and kidneys. 573. Anemia (Hb <70 g/l), leukopenia (leucocytes <3 x 10°/l), thrombocyto- penia (thrombocytes < 150x 10°/I). 4, Radiation disease and radiation damages (survived in the past). 5. Infancy (childhood). 6. Pregnancy. Relative contraindications: 1. Acute septic and infectious diseases. 2. Expressed spread skin diseases and inflammatory skin processes. CONTROL TASKS Questions for self-control 1. The basic principles of malignant tumors radiotherapy. 2. Sources of ionizing radiations used in medical practice. 3. Types of radiotherapy. 4, The classification of radiotherapy methods. 5. The radiation doses used for malignant tumors treatment. 6. Radiation reactions of the skin. 7. How is deep focal doses defining carried out? 8. The tolerant levels of organs and tissues irradiation and their practical sig- nificance. 9. Radiomodifiers, their application in radiotherapy. 10. The classification of tumors radiosensitivity according to B. Ye. Peterson. 11. The factors influencing the effectiveness of radiotherapy in non-neoplastic lesions. 12. The application of radiotherapy in non-neoplastic lesions. 13. The factors influencing the effectiveness of radiotherapy. 14. The contraindications for performing malignant tumors radiotherapy. 58CHARTER Y X-RAY THERAPY Xray therapy is a type of radiotherapy in which X-radiation is used for medi- cal purposes. X-ray therapy is performed in a roentgenotherapeutic room of a tadiotherapeutic department of a medical-prophylactic instituition (onco- logical dispensary, oncological centre), clinics, research institute and others. THE ARRANGEMENT OF A ROENTGENOTHERAPEUTIC ROOM Aradiotherapeutic department comprises roentgenotherapeutic rooms for performing long-focus and close-focus X-ray therapy as well as that with Bucky rays. A roentgenotherapeutic room is a totality of premises, apparatuses and auxiliary equipment for performing roentgenotherapeutic procedures. A roentgenotherapeutic apparatus consists of an X-ray tube, a current gen- erator, a support mechanism and a patient positioning table. THE USE OF CONES AND FILTERS An X-ray tube generates X-rays heterogenous by their penetrating capac- ity — long-wave quanta, the so-called “mild” irradiation which does not pen- etrate tissues depth but causes a biological effect (radiation damage) in super- ficial layers of organism's tissue. Short-wave X-radiation has a much greater energy, penetrates deep inside organism's tissue and is therefore used for per- forming X-ray therapy. To obtain a homogenous working beam of short-wave Xray they use copper and alumimium filters. According to the voltage under which X-rays are generated, it is necessary to use filters of various thickness; under the voltage of 120-150 kV they use aluminum filters with the thickness of 3-5 mm, while under the voltage of 160-230 kV — copper ones with the thickness of 0.5-2 mm. 59To restrict the area of the irradiation field and provide the constant source- skin distance (SSD), they use cones (Fig. 4.1 b) of various shapes and sizes, The dosimetric characteristics of the X-ray beam In X-ray irradiation of the skin field the maximum of the absorbed dose is located on the skin's surface, in tissue's depth the dose is permanently decreas- ing (Fig. 3.3 — “X-radiation’) at the expense of absorbing and disseminating radiation energy with tissue's molecules and atoms. METHODS OF X-RAY THERAPY Long-focus X-ray therapy Long-focus X-ray therapy is performed with the help of the RUM-17 X-ray apparatus (Fig. 4.1). By changing the voltage on the X-tube one can generate radiation of various penetrating capacity. Depending on the depth of the pathology in relation to the skin surface, long-focus X-ray therapy with the help of the RUM-17 apparatus is divided into: + Supreficial (used for irradiating the damaged area at the depth of up to 1 cm from the skin surface); the technical conditions: voltage — 100-120 kV, current strength 5-10 mA, the aluminum filter — 3 mm, SSD — 30 cm; + half-deep (used for irradiating the damaged area at the depth of up to 3. cm from the skin surface); the technical conditions: voltage 140-160 kV-, current strength — 10 mA, the copper filter — 0.5 mm + 3mm of aluminum, SSD — 40 cm; + deep (used for irradiating the damaged area at the depth of up to 5 cm from the skin surface); the technical conditions: voltage 200-230 kV, current strength — 10 mA, the copper filter 1 mm +5 mm of alumini- um, SSD — 50 cm; Close-focus X-ray therapy Close-focus X-ray therapy is used in the localization of the pathology at the depth of up to 1 cm from the skin surface. For obtaining the regime of close- focus X-ray therapy with the help of the RUM-7 apparatus (Fig, 4.2 a), one has 60Fig. 4.1. The RUM-17 roentgeno- therapeutic apparatus for long-focus X-ray therapy: the apparatus outward appearance: 1 — the X-ray tube ;2— the cone; 3— the current generator; 4 — the sup- port; 5 — the patient positioning table; b) the cones; ¢ the filters; d) the apparatus control panel to create the following technical conditions: voltage — 60 kV, the current strength 5-10 mA, SSD — 7.5 cm. In close-focus X-ray therapy they more often use aluminum filters of 0.1-3 mm and cones (Fig. 4.2 b) of various shapes and sizes. To close-focus X-ray therapy there is also referred therapy with ultrasoft X-rays — Bucky rays which are generated at the voltage of 10-25 kV. The pene- trating capacity of Bucky rays in the skin and mucous membranes does not ex- ceed 1.5 mm. They are used for the treatment of superficially located inflamma- tory processes, for example, in eczema and dermatitis of the scrotum and the mammary gland nipple, in blepharites and others. 61Fig. 4.2. The roentgenotherapeutic apparatus for performing close-focus X-ray therapy of the TA-O2: a) the apparatus outward appearance; b) filters; ¢) cones; d) the apparatus control panel X-RAY THERAPY OF MALIGNANT TUMORS The indications for applyning malignant tumors X-ray therapy: melanoma of the skin, skin cancer and carcinoma of the lip of stages | and Il, etc. X-ray therapy of skin cancer The histological forms — planocellular squamous, planocellular non-squa- mous and basal-cell cancer (basalioma). The classification of skin cancer according to the TNM system: T—a primary tumor, N — metastases in regional lymph nodes, M— remote metastases; T, —a primary tumor is not found out; T,, — carcinoma in situ; T, —a tumor with the diameter of up to 2. cm located superficially; 62T, — a tumor with the diameter of 2 to 5 cm, or insignificant infiltration of derma; T, —a tumor with the diameter of more than 5 cm, deep infiltration of der- ma; T, —a tumor damages a cartilage, muscles or bones; N, — regional lymph nodes are not damaged; N, — regional lymph nodes are damaged; M, — remote metastases are not found out; M, — remote metastases are present. The stages of skin cancer: Ostage —T,N,M,; Istage —T,N,M,; Istage — T,_ NOM; 2.3) Ill stage —T,N,M, or T,_.N,M,; IV stage —T,_,N, .M, The schemes of the patients’ standard treatment according to the Order of the Ministry of Health of Ukraine of 17,09,2007 N°554 "On the confirmation of giving medical aid protocols in the speciality “Oncology”. Stage | (T,N,M,) and stage Il (T, ,N,M,) 1, Surgical treatment — broad excision of a tumor with or without skin defect plastics; 2. X-ray therapy is independent: the total focal dose is 65-75 Gy. Stage Ill (T,NJM,;T,_,N,M,) 1. Surgical treatment — broad excision of a tumor with or without skin defect plastics and lymphadenectomy. Stage IV (T,_,N,_,M,) 1, The surgical treatment of the primary focus and remote metastases; 2. Palliative X-ray therapy: a) the primary focus — with the total focal dose of 60-75 Gy; b) metastatic damage — with the total partial dose of 30-40 Gy. The peculiarities of dosing and fractionated X-ray therapy and irradiation zones. Independent X-ray therapy A single focal dose is 3.5~4.0 Gy up to the total focal dose of 65-75 Gy (close-focus). Electronotherapy is more effective “Radiotherapy with high energy sources” (Chapter 5). In inoperable metastases to lymph nodes they use 63electronotherapy on a linear accelerator with the energy of electrons of 15- 25 MeV, SFD of 6 GY up to TFD of 60 Gy. But skin basaliomas — tumors with relatively benign development — are better cured with the roentgenothera- peutic method. The remote results of radiation treatment of skin cancer: a five-year survival with stage | — 97.9 %, with stage Il — 82.2 %, with stage Ill and IV — 34%. X-RAY THERAPY OF NON-NEOPLASTIC LESIONS The indications for the treatment of non-neoplastic lesions and the ground for the use of X-ray therapy — The general indications for prescribing X-ray therapy (Chapter 3). The doses and rhythm of X-ray therapy in non-neoplastic lesions: + in acute inflammatory diseases SFD is 0.25-0.5 Gy, TFD — 1-1.5 Gy; + in subacute inflammatory diseases SFD is 0.5 Gy, TID — 1,5-2 Gy; + in chronic inflammatory diseases SFD is 1 Gy, TFD — 15-6 Gy; + in degenerative-dystrophic diseases SFD is 1 Gy, TD — 3-5 Gy. The rhythm of irradiation: irradiation in acute inflammatory processes in the phase of infiltration is performed with the interval of 3-5 days and nights, in chronic inflammation and in degenerative-dystrophic diseases of the osteoarticular system irradiation is performed with the interval of 1-2 days and nights, in the exacerbation of the chronic process the intervals are enlarged up to 3 days and nights without changing the single dose value. X-ray therapy of osteoarticular panaris The objective: to remove perifocal inflammation of soft tissues and to re- strict the area of destruction. They use half-deep long-focus X-ray therapy: SFD is 0.25-0.3 Gy, TFD — 2.5- 3 Gy, the irradiation field is 6x8 cm. X-ray therapy of erysipelas In the non-complicated form of erysipelas they use superficial long-focus X-ray therapy: SFD is 0.2 Gy, TD — 1.5-2 Gy. 64In the complicated form of erysipelas depending on the depth of the sub- cutaneous fatty tissue, they use half-deep long-focus X-ray therapy: SFD is 0.2- 0.3 Gy, TFD — 2-3 Gy, or deep long-focus X-ray therapy: SFD is 0.3 Gy, TED — 4 Gy. X-ray therapy of periproctitis and rectal inflammatory processes The objective: the restriction of the infiltration focus, the acceleration of re- covery. In acute periproctitis they use deep long-focus X-ray therapy: SFD is 0.25~ 0.3 Gy, TFD — 1.5-2 Gy, the field is 6x8 cm (8x10 cm). In chronic periproctitis they use deep long-focus X-ray therapy: SFD is 0.4— 0.5 Gy, TFD — 1.5~2 Gy, the field is 6x8 cm (8x 10 cm). Radiation reactions and radiation damages in performing X-ray therapy (Chapter 3). CONTROL TASKS Questions for self-control The arrangement of the roentgenotherapeutic apparatus. The destination of cones and filters. The dosimetric characteristics of X-radiation. . The application of Bucky rays. . X-ray therapy for skin cancer of stage Il. . X-ray therapy for erysipelas. Qupens 65CHARTER M LONG-FOCUS RADIOTHERAPY THE STRUCTURE OF A LONG-FOCUS RADIOTHERAPY ROOM Long-focus radiotherapy is performed with the help of gamma-therapeutic apparatuses, generators of decelerating high energy radiation and generators of high energy corpuscular radiations (synchrophasotron, synchrocyclotron and others). In gamma-therapeutic rooms and high energy sources therapy rooms they apply the high energies of ionizing radiations, therefore the above mentioned rooms are placed in separate one-storey buildings, which enables to provide stationary protection by screening from the action of ionizing radiations. See the scheme of arranging a high energy sources therapy room in Fig. 5.1. Fig. 5.1. The scheme of arranging a gamma-therapeutic room (I= the treatment room; Il — the labyrinth; ll — the control panel room): 1 — the gamma-therapeutic apparatus; 2 — the television system of observation; 3 — the control panel The way to the the treatment room of the gamma-therapeutic room must lead through the labyrinth which doesn't allow direct radiation to get from the apparatus to the control panel room for antiradiation protection of the staff. 66In performing radiotherapy the patient's laying down (the relocation of the source at the necessay SSD, centration of the radiation beam) is a dangerous manipulation in terms of a high radiation background in the treatment room. During a radiation session the patient's observation is performed with the help of the television system. The malignant neoplasms treatment plan is made according to the radio- therapy course strategy (Chapter 3). In the preradiation period, after the patient's detailed examinatioin, the tu- mor's histological structure is found out. In the presence of a malignan tumor, they determine the indications and exclude the contraindications, after which the type and method of radiotherapy are determined. Depending on the his- tological structure, tumor's size, its development stage, location depth, they define an optimal SFD and TFD. In the radiation period the patient's irradiation is performed. When needed, additional treatment methods are applied. In the postradiation period the treatment results are evaluated and periodi- cal dispensary control is performed. EXAMPLES OF LONG-FOCUS RADIOTHERAPY FOR SOME MALIGNANT TUMORS Radiotherapy for lung cancer The classification of lung cancer according to the TNM system: T, — the primary tumor is not found out; T,, (in situ) — preinvasive carcinoma; 1 — the tumor is not more than 3 cm; T, — the tumor is more than 3 cm; germinates the visceral pleura or is ac~ companied by atelectasis; T, — the tumor of any size germinates the chest wall, diaphragm, mediasti- nal pleura, pericardium, pericardium, also concomitant atelectasis or obstruc- tive pneumonia are possible; T,— the tumor of any size spreads to surrounding organs, can be accompa- nied by malignant pleuritis; N, — there are absent signs of metastazing in regional lymph nodes; N — the damage of lymph nodes of the lungs on the pathologic process side; 67N, — the damage of the mediastinum lymph nodes on the side of patho- logic process or bifurcation lymph nodes; N, — the damage of the mediastinum lymph nodes or root of the lung on the opposite side or subclavicular lymph nodes; M, — remote metastases are absent; M, — remote metastases are present. The stages of lung cancer: O stage —T,NM,; iN My Istage —T, ,N,M,: listage —T,N.M,; lil stage —T,N,_M,; lV stage —T, ,N, M, The volume and‘ terms of standard treatment of the patients with the lungs small cell carcinoma is determined according to the Order of the Ministry of Health of Ukraine of 17.09.2007 N¢ 554 “On the confirmation of giving medical aid protocols in the speciality “Oncology”. The localized form of the disease — stage I-IIIB (T, ,.N, M,) 1. Chemoradiotherapy: chemotherapy — 4-6 courses and radiotherapy. 2. A complex treatment (I-Il stages): neoadjuvant PCT, surgical treatment and postoperative chemotherapy — not less than 4 courses. The spread form of the disease, stage IV (T, ,N, ,M,). 1. Chemotherapy. 2. Radiotherapy. The peculiarities of dosing and fractionating radiotherapy and irradiation zones Postoperative radiotherapy after palliative operations: SFD is 2 Gy, TFD — 50Gy Independent radiotherapy: Non-small cell lung carcinoma + I stage: SFD is 2 Gy, TFD — 40-44 Gy; + Il stage: SFD is 2 Gy, TFD — 74 Gy — for two stages. Small cell lung carcinoma SFD is 1.5-2 Gy, TFD — 60 Gy (twice in 24 hours after 3-4 hours; after bring- ing up 30 Gy irradiation is performed by a diminished field — SFD — 2 Gy, once in 24 hours). After irradiating of the primary focus there is performed irradiation of the brain: 68+ in the abscence of metastases: SFD is 2 Gy, TFD — 30 Gy; + in metastases to the brain: SFD is 3 Gy up to TFD — 30 Gy on the whole brain and locally SED — 2 Gy up to TFD — 50 Gy (with the account of previous fractions). Radiotherapy for breast cancer The classification of breast cancer according to the TNM system: T, — no tumor is found out; T, (in situ) — intraepithelial cancer; T. — the tumor's diameter is up to 2 cm, the skin is not damaged, the tumor is not fixed to the chest wall, the nipple is not retracted; T, — the tumor's diameter is 2 up to 5 cm, its mobility is restricted, the tu- mor is partially fixed to the chest wall, the nipple retraction can be observed; T, — the tumor's diameter is more than 5 cm, the tumor is fixed to the skin (the *orange crust” symptom), the tumor's fixation to the chest muscle; T, — tumors of any diameter with the fixation to the chest wall, the “orange crust” symptom; N, — the regional lymph nodes are not damaged; N — mobile axillary lymph nodes are palpated on the side of damage; Ni — immobile axillary lymph nodes are palpated on the side of damage; N, — the damage of epiclavicular and/or subclavicular lymph nodes on the side of damage, sometimes hand edema; M, — no remote metasases; M— remote metastases are present. The stages of breast cancer: 0 stage —T,.NJM,;7,N,Myi | stage —T,N.M,, ST NGM, i IIstage —T|N.M,; SNM: Ill stage —T,N,M,; T,NM,; IV stage —T,, "Ns iM, The volume. ‘and ‘terms of standard treatment of the patients with breast cancer is determined according to the Order of the Ministry of Health of Ukraine of 17.09.2007 N° 554 “On the confirmation of giving medical aid protocols in the speciality “Oncology”. Stage | (T,NoM,) Acomplex treatment: a) an organ-saving operation; b) postoperative radio- therapy on the peristernal, epiclavicular zones and the mammary gland; c) ad- juvant chemotherapy; d) hormonotherapy in hormonosensitive tumors. 69Stage ll (T,N,M,;T,N,M,) A complex treatment: a) one-time or five-time preoperative high-dose frac- tionated radiotherapy for the mammary gland; b) an organ-saving operation; ) postoperative radiotherapy; d) adjuvant chemotherapy and hormonothera- py in hormonosensitive tumors. Stage Ill (T, NJM,.T,N, M,) A complex treatment a) neoadjuvant polychemotherapy; b) surgical treat- ment; c) postoperative radiotherapy; d) adjuvant chemotherapy and hormono- therapy in hormonosensitive tumors. Stage lV A complex treatment: a) systemic polychemotherapy, or endolymphatic, or selective intraarterial polychemoherapy; b) palliative radiotherapy; c) surgi- cal treatment in the threat of tumor's disintegration; d) treatment with radio- pharmpreparations in bony metastases after indications; e) adjuvant chemo- therapy; f) hormonotherapy in hormonosensitive tumors. The peculiarities of dosing and fractionating radiotherapy and irradiation zones Preoperative radiotherapy: + the mammary gland (SFD — 2 Gy, TFD — 45-50 Gy); + the peristernal and epiclavicular areas (SFD — 2 Gy, TFD — 45 Gy); Postoperative radiotherapy after radical operations: + the tumor bed (after an organ-saving operation) (SFD — 2 Gy, TFD — 50 Gy); ¢ irradiation of the postoperative scar after mastectomy (SFD — 2 Gy, TFD — 40 Gy); the axillary area (SFD — 2 Gy, TED — 40 Gy); + the peristernal and epiclavicular parts (SFD — 2 Gy TFD — 45 Gy); Postoperative radiotherapy after palliative operations: + palliative radiotherapy (SFD — 2-2.5 Gy, TFD — 40-60 Gy per scar; + on the viae of the lymph outflow as well as bones damages (SFD — 4 Gy, TFD — 24 Gy (or SFD — 2 Gy, TFD — 30 Gy). Independent radiotherapy In counterindications for an operation there is prescribed radiotherapy after a radical program: + I stage: SED — 2-2.5 Gy, TFD — 40-45 Gy on the mammary gland and lymph paths; + Il stage: SFD — 2-2.5 Gy, TFD — 45-60 Gy on the mammary gland with the account of the first stage. 70Radiotherapy for rectal cancer The classification of rectal cancer according to the TNM system: T, — the primary tumor is not found out; T,, (in situ) — preinvasive carcinoma; T, — the tumor infiltrates the mucous membrane and submucous layer of the rectum; T, — the tumor infiltrates the muscular layer, without the limitation of the intestinal wall mobility; T, — the tumor germinates in all the intestine wall layers; T, — the tumor germinates in surrounding organs and tissues; N,— no damage of the regional lymph nodes; N, — metastases in 1-3 regional lymph nodes; N, — metastases in 4 and more regional lymph nodes; M, — no remote metastases ; M, — remote metastases are present. The stages of rectal cancer: O stage —T,N.M,; Istage —T, .NJM,; llstage —T, ,NM,i lll stage —T,_,N,_, Mg: IV stage —T, ,N,.M,- The schemes of standard treatment of patients with rectal cancer: © (T,NyM,), F(T,N,M,), I(T, ,NyM,) 1) a) surgical treatment; 2) b) adjuvant split radiotherapy — SFD 25-30 Gy; 3) surgical treatment. HWA (T, ,N,MQ), (T,NoM,), IIIB (T,N,M,), (T,_.N,M,) a) non-adjuvant split radiotherapy; b) surgical treatment; adjuvant chemoradiotherapy. \V (any T and N, M,) — palliative and symptomatic surgical treatment, pallia- tive radiotherapy and chemotherapeutic treatment. The peculiarities of dosing and fractioning radiotherapy and irradiation zone according to the Order of the Ministry of Health of Ukraine of 17.09.2007 Ne 554 “On the confirmation of giving medical aid protocols in the speciality “Oncology”. Preoperative radiotherapy: 1, TFD — 20-25 Gy, SFD — 5 Gy 2. TFD — 40-60 Gy, SFD — 2-2.5 Gy is performed for two stagesPostoperative radiotherapy after radical operations: TFO — 30-50 Gy, SED — 2-2.5 Gy Postoperative radiotherapy after palliative operations: TFD — 40 Gy, SFD — 2-2.5 Gy Independent radiotherapy: TFD — 60-70 Gy, SFD — 2~2.5 Gy is performed for two stages. RADIOTHERAPY WITH HIGH ENERGY SOURCES Electron-photon therapy Electron-photon therapy is performed distantly with the use of linear elec- trons accelerators (Fig. 5.2), betatrons generating electrons and deceletating radiation with the energy within the range of 1 to 45 MeV. The dosimetric characteristics of electrom radiation — Fig. 3.3. The dose necessary for irra- diation is chosen depending on the tumor location depth. In practice they distinguish low-energy linear accelerators (6 MeV) and high energy ones (18- 25 MeV). A modern linear accelerator is a combination of a linear accelerator and multiplate collimator (Fig. 5.3). The application of linear accelerators reduces Fig. 5.2. linear electrons accelerator outward appearance 72Fig. 5.3. A multiplate collimator of the "Varian" firm as much as twice the number of neoplasms relapses and radiation reactions as compared to the irradiation on devices with cobalt. New radiotherapy technologies introduced into practice, for example IGRT (Image Guided Radiation Therapy), IMRT (Intensity-Modulated Radia- tion Therapy) and PVI (Portal Vision Imager) enable to control visually the accuracy of irradiation in the real time regime in the process of perform- ing each treatment session with the help of a kilovolt radiation source con- nected to a linear accelerator. It is important to note that the opportunities of the clinic application of the linear accelerator with a multiplate collimator (the width of the plate is less than 0.5 cm) are much wider than those of a gamma and cyberknife. With help of this apparatus one can form itradia- tion fields sizes from 5 x 5 mm to 40 x40 cm, which extends significantly the range of its application in oncology: there is the possibility to treat foci of any size. Since the beginning of the 21* century the commonly acknowledged tra- ditional fractionated gammatherapy “Co has been gradually replaced by elec- tron-photon therapy on linear accelarators of various types and decelerating irradiation of variuos energies. Electron therapy is indicated both in superficially located (skin cancer, the oral cavity mucous membrane, penis, vulve, breast cancer relapses, malignant 73limphomas of the skin, cancer metastases to superficial lymph nodes) and deeply located (cancer of the lungs, brain, esophagus, kidneys and others) malignant neoplasms. They use traditional fractionating SFD 2 Gy up to TFD 50-60 Gy for two stages. Neutron therapy Neutron therapy is a type of corpuscular radiotherapy which is performed with help of neutron radiation. In the interaction of neutron radiation with a substance there prevail the processes that lead to ionization with a high lin- ear energy transmission, therefore it is also called densely-ionizing “The mate- rial ~ neutrons interaction (Chapter I)". For neutron therapy they use neutron generators for irradiation and neu- tron-generating RP. The average neutron energy in a free space is equal to 10.2 MeV, at the depth of 5 cm — 7.8 MeV. The depth of the dose half-weakening in tissues is equal to 9.5. cm. In neutron therapy they use long-focus, intracavitary and interstitial irradia- tion. Neutron therapy is performed with the help of cyclotrons. They use neu- tron rays with the energy of 6-15 MeV in the dose capacity of 0.1 Gy/min at the distance of 1 m. The peculiarity of the neutron radiation biological effect is the insignificant dependence of the treatment effect on a cellular cycle stage and oxygen partial pressure in the tissues being irradiated. This facilitates the destruction of malignant tumors the radioresistance of which is conditioned by the cells which divide slowly and the cells that are in the state of hypoxia. SFD in neutron therapy is 0.8-1.8 Gy, TFD — 15-25 Gy. To distant irradiation they refer Boron neutron capture therapy. A therapeutic effect emerges as a result of capturing thermal or intermediate neutrons with the energy of less than 200 keV by the nuclei elements previously accumulated in a tumor (for example,"8) which capture neutrons and disintegrate releasing a-particles creating the high density of ionization. This enables to bring up a significant dose of irradiation to a tumor. Intracavitary and interstitial neutron therapy (brachytherapy) can be per- formed with help of the source of mixed neutron and gamma radiation Cf {in patients with cervical cancer, tongue cancer and mucous membrane cancer of oral cavity). 74Proton therapy Proton therapy is a type of corpuscular radiation energy based on the ap- plication of high-energy protons (50-1000 MeV) accelerated on synchropha- sotrons and synchrocyclotrons (Fig. 5.4). Proton therapy is used for irradiating distinctly delimited pathological foci as well as for irradiating deeply located tumors when the irradiation zone is entered by a large volume of healthy tis- sues. Proton therapy is applied for irradiating intracranial tumors of small vol- ume (for example, hypophysis adenoma, eye tumors and others). The tumor is irradiated momentarily from many source positions, due to which in the focus there is created a significant radiation dose (up to 100 Gy). Proton therapy is also applied for the treatment of cervical cancer as well as that of the nasopharynx, prostate gland and others. Fig. 5.4. The cyclic protons accelerator: 4a) the scheme of the accelerating protons camera in the synchro- cyclotron 1 — the proton source, 2— the proton beam, 3— the injector, 4 — the accelerating camera, 5 — the accelerating magnets, 6 — the declining magnet, 7— the accelerated proton beam, 8 — the irradiation object, the movement direction ofprotons — the arrow, the accelerated movement direction of protons —~ the double arrow): ) patient positioning for performing proton therapy 75Pi-meson therapy Pi-meson therapy is based on the application of pi-mesons (negative nuclear Particles) which are characterized by high biological effectiveness per dose unit. Stereotaxic radiosurgery Stereotaxic radiosurgery Stereotaxic radiosurgery is the destruction of the areas of damage (tumor) due to the highly accurate delivery of a high single irradiation dose. In radiosur- gery there are used some types of apparatuses: modified linear accelerators of the “Trilogy” type (Fig. 5.5), Leksell gamma-knife (Fig. 5.6), photon cyberknife (Fig. 5.7) The method's advantages: + no necessity to apply invasive (open) surgery; # no need in general narcosis; + the patient can be discharged on the day the treatment was per- formed; + it allows, in most cases, to avoid the radiation damage of healthy tis- sue beyond a tumor. Fig. 5.5. The linear accelerator “Trilogy” of the “Varian” firm 76Fig. 5.6. The gamma-knife, the ourward look of the apparatus Sieg emerg Fig. 5.7. The Cyberknife G4 system Leksell gamma-knife Leksell gamma-knife (Fig. 5.6): at the basis of the apparatus there is laid the method of radiation stereotaxic directing at the object being irradiated which is performed with 201 source of radioactive cobalt (Co) with the help of a ste- reotaxic frame fixed above the irradiation zone and a system of lenses. Irradia~ tion, separately from each source, is focused at one point (isocentre) where it creates the total dose sufficient to obtain a desired biological effect in the path- ys gological area without damaging surrounding healthy brain tissues (Fig, 5.8). The advantage of the method is the absence of anasthesiological, surgical Postoperative and radiation complications risk. The duration of the treatment is from 40 minutes to 3-4 hours depending on the number of damage foci, the tumor's volume, its histological form and degree of malignancy. Errors or inac- curacies in radiation with a gamma-knife do not exceed 0.15 mm. The indications: 1. Primary brain tumors with the size of up to 3. cm (malignant and some benign). 2. Multiple metastatic brain damages. 3. Arteriovenous brain malformations. Fig. 5.8. A schematic image of Leksell gamma-knife Cyberknife Cyberknife (Fig. 5.7) was invented in 1992 by John R. Adler, Professor of Neurosurgery and Radiation Oncology of Standfort University. The first patient was treated in 1994. The two main principles are applied in the cyberknife con- struction: the generation of electromagnet radiation with the help of a linear electrons accelerator (photon energy — 6 MeV and a robotized manipulating instrument which allows to bring up ionizing radiation to any part of the hu- man's body from various directions. The number of directions in which the manipulator directs the accelerator reaches 1400. In the practice of stereotaxic radiation therapy planning 100-300 directions usually suffice. The wide range of the robotized manipulating instrument mobilitiy is provided by three lin- ear directions of movement (top-down, right-left, forwards-backwards and 78three rotation directions (roll, pitch, yaw), that is it has 6 degrees of movement freedom. The imaging table (Robo-Coach) on which the patient is placed also has 6 degrees of movement freedom. In this the linear accelerator manipulat- ing instrument can with high accuracy (up to a millimeter part) direct irradia- tion and locate the accelerator in various positions. The patients’ topometric preparation for performing stereotaxic radiosurgery (one fraction) and radio- therapy (2-6 radiation fractions) is performed with the use of a series of com- puter (512 CT contrast tomograms with a step of 1.5 mm) on CT anda series of magnetic resonance tomograms (MRI with a step of 1.5 mm) with contrast. To recreate a three-dimension anatomo-topographic image of the needed area of the head or human body with a pathological focus there is performed the procedure of CT and MRI-tomograms fusion in three projections (sagittal, coro- nary, axial). This procedure provides the filigree accuracy of the pathologic fo- cus configuration, surrounding healthy tissues and critical organs finding out ‘on each section, Modified linear accelerators Modified linear accelerators can function in both surgical (a single dose is 15-25 Gy, the tumor's size is up to 3-4. cm), and therapeutic (3-6 fractions with 5-20 Gy each, the tumor's size is more than 3-4 cm) regimes. The application of radiogsurgical methods supposes keeping to some basic principles and requirements: + getting a complete information on the degree of the tumorous process spreading for finding out the necessary irradiation volume which requires at the stage of preradiation preparation the use of CT-, MRI- and PET-methods of investigation as well as a CT- or MRI- stimulator; + computer dosimetric planning with the choice of type (gamma, pho- ton or electron) and radiation; * energy and creating a computer three-dimensional inversive image (model) of a tumor; + multiple verifications of the irradiation zone before and in the pro- cess of radiation treatment, the possibility of the image confron- tation with diagnostic imaging data for correcting the irradiation plan; the application of fixing devices to make recreating patients' radiation sessions possible; 79Radiosurgical methods of oncological patient's treatment can be performed both within one and several radiation sessions (fractional irradiation — 2-5 procedures and more) depending on the apparatuses applied for that. CONTROL TASKS Questions for self-control 1. Characterize gamma rays energy distribution in organism tissues. 2. Write down the plan of lil stage small cell lung carcinoma treatment. Write down the plan of Il stage rectal cancer treatment. 3. The types of radiotherapy with high-energy sources. The advantages of the radiosurgical treatment method. 80| A) BRACHYTHERAPY THE ARRANGEMENT OF A CONTACT RADIOTHERAPY ROOM The scheme of arranging a room for performing intracavitary contact radio- therapy with the help of a hose apparatus (Fig. 6.1). The apparatuses, radiation sources for contact methods — Chapter 3. Fig. 6.1. The scheme of arranging a room for performing intracavitary contact radiotherapy (| — the apparatus room, ll —the labirynth, Ill — the control panel room, IV — the treatment room; 1 — the apparatus for intracavitary gamma-therapy, 2— the television observation system, 3— the patient's armchair, 4 — the table for endostates, 5 — the control panel) THE METHODS OF CONTACT RADIOTHERAPY 1. The intracavitary method of radiotherapy The intracavitary method of radiotherapy is applied in malignant tumors of the oral cavity (alveolar cancer, tongue cancer, palatal cancer, labial cancer, buccal mucous membrane cancer and others) as well as that of the esoph- 81agus, rectum, vagina, uterus and cervix uteri. The radiation source is placed maximally close to the tumor. The immediate contact of the radiation source enables to obtain a high absorbed dose in endostates the pathological area (Fig. 6.2). Fig. 6.2. The location of gamma preparations in the endostate in performing gamma- radiotherapy of the upper and middle third of the esophageal cancer (an X-ray image in the right oblique projection) The methods of intracavitary gamma-therapy supposes the use of a hose apparatus for intracavitary gamma-therapy. To exclude the immediate per- sonnel's contact with closed radiation sources, they use the “Afterloading’” method (consecutive introducing). First, the endostate is introduced into the lumen (Fig. 6.3) and fixed in a needed place without a radiation source, then connected to the apparatus hose, after which they switch on (from the hose therapeutic apparatus control panel) the mechanism of transporting radioac- tive preparations from the apparatus shelter to the endostate. 2. The interstitial method of radiotherapy Interstitial gamma-therapy Radioactive gamma preparations (closed or open radiation sources) are in- troduced immediately into the tissue of a tumor. 82They use the following forms of closed radioactive preparations: needles, beads, tubules, suture material with granules Co and others (Fig. 64). The interstitial method is indicated both as an independent method and in a combination with radical or palliative surgical intervention in breast cancer, lung cancer, malignant tumors of soft tissues and others. Fig. 6.3. The endostates for intracavitary gamma-therapy ahermetic case i ITIL LLU fe an active substance | (fe, ah active substance MS ' LL Perr TTT an eye Fig. 6.4. The scheme of a radioctive needle In the interstitial method of radiotherapy there is created a high dose of ir- radiation in the tumor, whereas in surrounding tissues the energy absorbed is significantly lower. For creating an even dose field, individual radioactive prep- arations are introduced into a tumor and around it in parallel rows in 1-1.2 cm from each other in the form of a triangle or other figures and left for 6-7 days and nights until TFD of 60-70 Gy is achieved (non-stop irradiation). 83Interstitial beta-therapy Interstitial beta-therapy is performed with the use of open RP (colloid so- lutions and suspension of radionuclides "Au, silicate ®Y, zirconium phos- phate or chrome phosphate with #P). Obtaining RP — Chapter 9. Using spe- cial tools, they introduce syringe needles into a tumor in parallel rows at the distance of 0.6-1.2 cm from each other; the needles being removed after RP has been introduced into tissues. The doses are calculated with the use of mathematical formulae. RP gets to the regional lymph nodes through lym- phatic tracts where there occurs potential radiating of metastatic cancer cells. 3. The stereotaxic interstitial method The stereotaxic interstitial method of contact radiotherapy is the deploy- ment of radioactive preparations in the tumor bed (after its removal) during surgical intervention. After irradiation has been over, the preparations are re- moved, It is performed by implanting many radiation sources into a tumor, such as Ir, 51 and others. Together, these implanted sources create the irradiation field which corresponds completely to the target's (tumor's) vol- ume. Under such conditions, the tumor is irradiated with lethal doses, while surrounding non-damaged tissues receive a significantly less absorbed dose. This method is mainly applied as a component or addition to long-focus ir- radiation in the form of a “boost” in tumors which do not exceed 5 cm in diameter. The method is widely applied in treating I-Il stages of prostate cancer: under the control of ultrasonic investigation they evenly implant crystals into the organ tissues: '?3| (the RAPID Strand system). 4. The intraoperational method The intraoperational method is irradiation of the tumor bed (after its re- moval) during operative intervention. For intraoperational irradiation they use the same sources as in interstitial therapy. After irradiation is over, the prepara- tions are removed. The main goal of the given method is to influence residual microscopic tumor tissues and to prevent possible metastasizing from the pri- mary focus zone. 845, The application method The application method is the method of contact radiotherapy in which ra- dioactive preparations are deployed on the damaged area of the patient's body surface. It is used in superficially located malignant tumors at early stages of their development (cancer of skin, oral mucous membrane, lower lip). Radioac- tive or gamma radiation sources are located in the thickness of the previously manufactured plastic applicator which corresponds to the shape of irradiation area, The sources in the applicator are placed evenly, most othen in one plane as a rectangle or a polygon. The applicator is fixed in the focus of pathological area. Irradiation is performed daily during 4-6 hours depending on the dose power of the radiation source. 6. Radionuclide therapy Radionuclide therapy is a separate method of treating a row of benign and malignant tumors with the help of open sources: #P, "1, Sr, "Sm, "Au. This method is worldwide referred to the speciality “Nuclear Medicine” and in Ukraine — “Nuclear Imaging’ (Chapter 7). The essence of the method is that introduced intravenously or per- orally radiopharmaceutical preparations in therapeutic (not diagnostic) doses accumulate selectively in tumors or specific organs and at the expense of beta-radiation create a needed absorbed treating dose. The main condition of treatment is the application of beta-irradiators, or sources with a beta-component, for creating a maximally absorbed dose in the target. The indications for using radionuclide therapy 1. The complex treatment of highly-differentiated tumors (follicular and papillary cancer) of the thyroid gland ("*"1). . The treatment of thyrotoxicosis ('7"1). |. The treatment of various metastases of tumors (especially hormone- dependent) in bones (”P, Sr, Sm). The treatment of metastastatic plurites and ascites (intrapleural intro- duction) — ‘**Au. . The treatment of true polycythemia (”P). wn ~~ a 85Radionuclide therapy is performed in special departments of oncological clinics where there are conditions for running and observing the patients while giving them high treating doses of appropriate RP (3500 MBq "I, 500 MBq "sr, 200 MBq '“Au); these doses need the patient's isolation for the term of from 5 days (Sr) to 2 weeks (2P, 12"), '8Au), The basic conditions for these departments functioning: + the “active zone” — the wards where the patients are staying; this zone is linked telecommunicationally with the nurse and aid-woman's post; * the “clean” zone — the place where the department personnel are staying; + the “active” zone, where treating activities of RP are dealt with, there must be a separate sanitary inspection room, lavatory and bathroom which are separated with a lobby from the “clean” zone; + at the exit from the “active” zone to the “clean” one there must be a post of radiometric control of the personnels hands, special clothes and footwear contamination; + for removing liquid wastes from this department to canalization there must be precipitation tanks where wastes are detained up to the lev- els allowed by the Basic Sanitary Rules of Ukraine (BSRU). EXAMPLES OF USING CONTACT RADIOTHERAPY IN TREATMENT OF SOME MALIGNANT TUMORS Radiotherapy for esophageal cancer The classification of esophageal cancer according to the TNM system: T, — no primary tumor is found out; T,, — preinvasive carcinoma: an intraepithelial tumor without invasion of the basal membrane (carcinoma in situ); T, —a tumor infiltrates the mucous membrane and submucous layer of the esophageal wall; T, —a tumor infiltrates the mucscular membrane of the esophageal wall; T, —a tumor infiltrates the layers of the esophageal wall; T, —a tumor spreads to the adjacent structures of the mediastinum; 86N, — no metastatic damage of the regional lymph nodes; N, — metastatic damage of the regional lymph nodes is present; M, — no signs of remote metastases; M, — remote metastases are present. The stages of esophageal cancer: O stage —T,.N.M,i | stage — T,N.M,; Iistage —T,_,N, Moi lllstage —T, ,N,_Myi IV stage — any T, any N, M,. The schemes of treating patients with esophageal cancer (the cervical and upper thoracic parts) according to the Order of the Ministry of Health of Ukraine of 17.09.2007 N° 554 “On the confirmation of giving medical aid protocols in the speciality “Oncology”. A. The cervical and upper thoracic parts Stage I-ll + long-focus radiotherapy (LFRT) as independent treatment, SFD 1.8— 2.Gy, 5 times a week, TFD 60-65 Gy; * united radiotherapy (SFD 45-50 Gy + intracavitary gamma-therapy up to TFD 70-75 Gy); * polychemotherapy. B. The middle thoracic, lower thoracic and abdominal parts Stage I-Ill * preoperation LFRT: SFD 40-45 Gy in the classical regime of fractionat- ing (SFD 1.8-2 Gy, 5 times a week); + surgical treatment (in 2-3 weeks after RT is over); + polychemotherapy. Stage IV ‘ symptomatic operation (gastrostomia); + palliative RT (SFD 40-45 Gy); + palliative CT. The peculiarities of dosing and fractionating radiotherapy and irradiation zones Preoperative radiotherapy: TFD 30 Gy with medium fractions (SFD 2-2.5 Gy) to the whole esophagus, mediastinum and a celiac trunk zone. 87Postopeartive radiotherapy after radical operations: TFD 30 Gy with medium fractions (SFD 2-2.5 Gy) to the whole esophagus, mediastinum and a celiac trunk zone. Independent radiotherapy: TFD 60 Gy (within 2 stages with the interval of 2 weeks) with medium fractions (SFD 2-2.5 Gy) to the whole esophagus, mediastinum and thea celiac trunk zone. Radiotherapy in schemes of chemoradiation treatment: TFD 60 Gy (within 2 stages with the interval of 1 month) with medium frac- tions (SFD 2-2.5 Gy) to the whole esophagus, mediastinum a celiac trunk zone. Radiotherapy for cervical cancer Among malignant tumors of the female gonades, cervical cancer occupies the first place. The classification of cervical cancer according to the TNM system: T, — no tumor is found out; T,, — carcinoma in situ; T, — carcinoma is restricted by the cervix uteri; T, — carcinoma is spread beyond the cervix uteri but does not reach the pelvis walls or spreads to the vagina up to its lower third, does not infiltrate or infiltrate the parametrium; T, — carcinoma is spread to the lower third of the vagina and/or spreads to the pelvic walls, hydronephrosis as a result of squeezing the ureter by a tumor is possible; T, —a tumor is spread to the bladder mucous membrane or the rectum, or is spread beyond the small pelvis; N, — no metastases in the regional lymph nodes; N, — metastases in the regional lymph nodes are present; M, — no remote metastases; M, — remote metastases are present. The stages of cervical cancer: 0 stage —T,,N.M, I stage —T,NJM,: Ilstage —T.N.M,; Ill stage —T,.N\M,; lV stage —T, ,N,M, In 1938 M. C. Tod and W. J. Meredith suggested performing the dose calcu: lation while planning radiotherapy for cervical cancer using two conventional 88points A and B located at the level of the left cervix uteri fauces (Fig. 6.5). Point Ais located 2. cm more laterally than the median axis of the uteral canal (O), point Bis located at the same level and remoted 5 cm laterally from the median axis of the uterus (the zone of the parametral cellular tissue lateral parts and the lymph nodes of the lateral pelvic walls). Fig. 6.5. The scheme of points 0, A, and 8 location in planning cervical cancer radiotherapy Stage 0- 1. Surgical treatment. 2, Intracavitary radiotherapy (the method of choice) — 40 Gy to point A. Stage ll |. Combined treatment: + preoperative intracavitary radiotherapy; SFD 10 Gy on point A, TFD — 20 Gy within 2 fractions with the interval of 7 days — after 24-48 hours; * surgical treatment (in 2-3 weeks); + postoperative long-focus radiotherapy to the area of the small pelvis with TFD of 40 Gy (SFD 1.8-2.0 Gy, 5 times a week). Il. United radiotherapy is an alternative method of treatment — (long-focus radiotherapy — 15 Gy to points OAB, 40 Gy to point B (possibly against the background of radiomodifiers), intracavitary radiotherapy 50 Gy to point A, 89or TFD — 75 Gy to point A, 65 Gy to point B in the presence of regional lymph nodes metastatic damage). Stage Ill T,,NJM, United radiotherapy (possibly against the background of radiomodifiers) — TFD 80-85 Gy to point A, 65 Gy to point B. Stage IV —T,, any T in M, — pallitive course of polychemotherapy Palliative courses of radiotherapy and polyhemotherapy in the absence of contraindications and advisability of their application The peculiarities of dosing and fractioning radiotherapy and the doses of irradiating patients with cervical cancer is determined according to the Order of the Ministry of Health of Ukraine of 17.09.2007 N° 554 “On the confirmation of giving medical aid protocols in the speciality "Oncology". Preoperative radiotherapy: SFD 10 Gy to point A, TFD — 20 Gy within 2 fractions with the interval of 7 days to the area of the small pelvis TFD up to 40 Gy (SFD 2.0 Gy, 5 times a week). Adjuvant therapy after radical operations: + United radiotherapy: long-focus radiotherapy (possibly against the background of radiomodifiers) TFD 15 Gy to points OAB, 42-44 Gy to point B, intracavitary radiotherapy — 50 Gy to point A or, in the pres- ence of regional lymph nodes metastatic damage, TFD 75 Gy to point A, 65 Gy to point B. Independent radiotherapy: + United radiotherapy (possibly against the background of radiomodi- fiers) — TFD 80-85 Gy to point A, 65 Gy to point B. Radiotherapy in schemes of chemoradiotherapy: + Long-focus irradiation of the small pelvis with SFD 2 Gy 5 times a week TFD up to 30 Gy within 15 fractions against the background of chemo- therapy. Five-year survival after radiotherapy of cervical cancer at the first stage = 90 %, at the second stage = 60 %, at the third stage = 35 %. On the average, for all the stages of cervical cancer five-year survival is =58 % of observa- tions. Radionuclide therapy for thyroid cancer The classification of thyroid cancer according to the TNM system: T, — a tumor is not found out; 90T,, — carcinoma in situ; T —a single node in one lobe of the thyroid gland without limitation of its mobility; T,— multiple nodes in onelobe with or without deformation of the gland, without limitation of its mobility; T,— tumor damages tboth lobes of the gland with or without deformation of the gland; T, — the tumor is spread beyond the gland capsule; Nj, —no signs of regional lymph nodes' damage; N,_,— metastazing to the regional lymph nodes is found out; M, — no remote metastases; M, — remote metastases are present. The stages of thyroid cancer: Stage | —T,N.M,; Stage il —T, .N.M,i Stage Ill —T,N.M, ort aM Mai Stage IV—T,_,N, The schemes of treating patients with thyroid cancer according to the Or- der of the Ministry of Health of Ukraine of 17.09.2007 Ne 554 “On the confirma- tion of giving medical aid protocolsin the speciality “Oncology”. Papillary and follicular cancer Stage !—T,,N, 1, Surgical treatment. Stage |—T,,N,M,;IV—T, NM, 1. Surgical treatment — thyrodectomy. 2. Suppressive hormonotherapy. Stage ILIV—T,_.N,M, , 1. Surgical treatment. 2. Radioiodotherapy. 3. Suppressive hormonotherapy. Medullary cancer Stage |—T,N.M, 1. Surgical treatment. 2. Radiotherapy Stage ll-IV—T,_,N, .M, . Surgical treatment. 2. Radiotherapy — long-focus gamma-therapy to the zone of the primary focus and regional lymph nodes, SFD 2.0 Gy up to TFD 50-60 Gy. 91Undifferentiated cancer Stage IV—T,_,N,M, , 1. Surgical treatment. 2. Radiotherapy (long-focus gamma-therapy) to the zone of the primary focus and regional lymph nodes, SFD 2.0 Gy up to TFD 50-60 Gy. 3. Adjuvant chemotherapy. The peculiarities of dosing and fractionating radiotherapy and irradiation zones Long-focus gamma-therapy: SFD — 2 Gy, TED — 55-60 Gy. Radioiodotherapy in papillary and follicular forms of cancer of II-IV stages (T, ,N,.M,,) 1 activity 1.8-4.0 GBq (1800-4000 MBq). Radionuciide therapy for multiple metastases Bones are most often metastasized by: breast cancer, hypernephroid can- cer, lung cancer, prostate cancer, rectal cancer, thyroid cancer, uterine cancer, skin cancer and others. The indications for radionuclide therapy — patients with multiple metasta- ses of malignant tumors of various localizations in bones: + damages of bones in myelogenetic disease; + systemic (multiple) bone tumor diseases in the presence of a sharp pain syndrome. Long-focus radiotherapy is effective in single meatastases. LFRT of single metastases: SFD 2-3 Gy up to 40-60 Gy. In multiple metastases in bones there is effective united radiotherapy: os- teotropic RP and long-focus gamma-therapy of damaged bones’ parts. They use metastron (*Sr chloride) or #P as osteotropic RP. Metastron (the agent is Strontium-89). Strontium-89 is a beta-radiator, a physiological analog of Ca** with selective accumulation by osteoblastic bone metastases (it is detained in it for about 100 days), is not metabolized. The ac- tion mechanism is conditioned by the direct damaging action of beta-particles on cells of metastases. The preparation is introduced once intravenously with the activity of 150 MBq. In using *P with the therapeutic activity of 333-544 MBq, pain decreases or stops in most patients with multiple damages of bones, the general state gets improved, and in some patients the capacity for work is temporarily restored. 92Since recently the radionuclide therapy methods with #P and ®Sr have been combined with the introduction of modifiers (chemotherapeutic) and bisphoshonates which improve significantly the median of survivability and enlarge the periods of pain-free patients’ remission. CONTROL TASKS Questions for self-control 1. The methods of contact radiotherapy (brachytherapy). 2. The stereotaxic interstitial method of brachytherapy. 3, Radiotherapy for cervical cancer of II stage. 4. Radionuclide therapy for cancer metastases in bones. 93Methods of Diagnostic Imaging. The Physical Basics of Diagnostic Imaging Chapter 7. Nuclear Imaging Chapter 8. X-ray, CT, MRI and Ultrasound Imaging Diagnostic imaging studies the application of ionizing and non- fonizing types of radiation for the investigation of human organs and systems structure and functions. The usage of ionizing radiations (quantum and corpuscular) is at the basis of X-ray. CT, SCT and nuclear imaging methods, while the use of non-fonizing irradiations (ultrasound and resonance) is at the basis of ultrasound and magnetic resonance methods of investigation.CHAPTER NUCLEAR IMAGING Nuclear imaging (radionuclide diagnostics) is a section of medical radiol- ogy which studies methods of studying the morphology and functions of hu- man organs and systems with the help of radiopharmaceuticals (RP). RP are the radionuclides or tagged chemical compounds in which part of neutral atoms are replaced by radioactive ones. The chemical properties of ra- dionuclides are identical to the properties of stable chemical elements, there- fore their metabolism in the organism is the same, which enables to study the metabolism of the appropriate stable substances. In nuclear imaging they use the very small weight quantities of radionu- clides (hundred quadrillionth parts of gram). Such small weight quantities got the name of indicatory quantities, while the irradiation doses conditioned by them are called indicatory doses. Indicatory doses of irradiation do not violate the normal course of vital processes. OBTAINING RP Radionuclides are obtained with the help of nuclear reactors or cyclotrons. After purification and finding out a radionuclide's specific activity (the radio- nuclide contents in a unit of the basic substance mass), they are transported in hermetically closed ampoules in special protective containers to radiological laboratories. For obtaining RP there are also applied generative systems. The basic ele- ments of a RP generator are: a protective casing, a column with the maternal radionuclide and a system of communications (Fig. 7.1). The daughter short-lived radionuclide formed as a result of the maternal ra- dionuclide decay is washed out of the generator. They use more often genera- tors of "Tc (the maternal radionuclide Mo), *”"Sr (the maternal radionuclide 87Y), ™™In (the maternal radionuclide '"Sn), '*21 (the maternal radionuclide Te) and others. The half-decay periods (T,,,) of the radionuclides mentioned — Table 7.1. 95a vacuum vial a vial with an eluate ~ a bacterial filter ~~ an air filter a lead protective container .. a column with a maternal radionuclide Fig. 7.1. The scheme of a radionuclide generator Depending on the duration of the period of half-decay, RP are divided into: Jong-lived (T, is more than two weeks), for example, "Se —T,,, = 120 days and nights, short-lived (T,,, is from one hour to two weeks), for example Te — T,, = 6 hours, #P —T,,, = 14.3 days and nights) and ultrashort-lived (T,,, from some minutes to some hours, for example, “O — T,,, = 2.03 rites "C—T,,,=20.1 minutes). The ways of introducing RP into the organism: enteral inhalation, intrave- nous, intrarterial, into lymphnodes, intracutaneous, subcutaneous, into the ce- rebrospinal canal. The basic characteristics of RP and radiation load on critical organs — Table 7.1. METABOLISM OF RP An RP introduced into organism is evenly distributed in the blood and then, if there is present tropicity to some organs or tissues, accumulates init. They distinguish organotropic RP ('31l, Au-colloid and others), tumoro- tropic RP (°"Tc-pertechnetate, °’Ga citrate) and others and without expressed selective accumulation (Na, *H and others). They distinguish aimed organo- 96Table 7.1. The basic characteristics of RP and radiation loads on critical organs The radio-| —T,, Compounds The critical organ The radiation nuclide load, mSv/ MBq »p 14.3days | Disodium —_| The organism as a whole 27 and nights| phosphate The gonades 18 The red bone marrow 45 "Ga 3.26 days Citrate The red bone marrow 0.15 and nights Se 120.4 days| Selenium The liver 62 and nights | methionine The kidneys 62 Te hours | Pertechnetate The thyroid giand 0.014 Pyrophosphate The liver 0.092 Tetrofosmin The skeleton 0.0094 Limphosis The spleen 0.057 Technomec The gonades 0.0015, 2p) 2.8 days Citrine The kidneys 0.016 and nights The red bone marrow 0.0017 inn) 99.8 Citrine The liver 0.10 minutes The organism as a whole 0.0025 ay 8.06 days | Sodium iodide The thyroid gland 570 and nights The gonades 0.058 The kidneys 0.075 The organism as a whole 0.0049 The large intestine 9.4 The liver 0.22 13] 13.3 hours| Sodium iodide The thyroid gland 320 The gonades 0.044 The kidneys 0.64 The organism as a whole 0.038 The liver 2Xe 5.29 days The lungs 0.011 and nights The gonades 0.00035 tropicity (an RP accumulates in a certain organ, for example, *"Sr in bones) and indirect organotropicity (the RP concentrates along the way of its excretion, for example, rose bengal tagged !""lin the liver). 97THE REQUIREMENTS FOR RP IN TERMS OF CLINICAL USE Radionuclides or radionuclide compounds which are involved in metab- olism or transported by blood flow must reflect the function of the organ- ism or an individual organ, The application of RP must be physiologically grounded. An RP must be not harmful to the organism and be quickly excreted from it, that is the effective period T_,— the period during which the activity of the preparation excreted from the organism will be diminished as much as twice at the expense of decay and excretion from the organism, it must be as short as possible. The most acceptable are RP with T,,from 6-24 hours up to 10-30 days, Dur- ing this period no significant irradiation of tissues occurs, but still there is an opportunity to study the functions of the organism in dynamics. RP must not contain toxic admixtures or radionuclides which form long- lived daughter products in the process of decay. An RP must radiate such particles or photons which are convenient to regis- ter with the help of modern equipment. Radionuclides radiating alpha-particles are not appropiate for diagnostic imaging because of their insignificant path length in tissues. It is those radionuclides came to be used which are able to radiate gam- ma quanta: gamma radiation is partially absorbed by tissues, partially goes outwards and can be registered with the help of appropriate radiometric de- vices, The most widespread in nuclear imaging are currently the compounds tagged "Tc for the diagnosis of brain tumors, studying central and peripheral hemodynamics, investigating the thyroid gland, skeletal system, other organs and tissues. 11, 31 and their compounds are applied for the investigation of the thyroid gland, liver and kidneys’ function. *'Cr are used for hematological research. Col- loid solutions and macroaggregates *"Tc, "I, "In are applied for investigat- ing lymph nodes and the liver. Xe is used for the investigation of the lungs, peripheral hemodynamics, the blockade level of the spinal cord subarachnoid space. Compounds, tagged *5Se, #P, "In, "Ga are widely used in oncology. The fundamental scheme of nuclear imaging — Fig, 7.2. 98RP_ | >| Anobject }—>|__ A radiation receiver | ‘An expert in nuclear imaging <—| A registering device Fig. 7.2. The scheme of nuclear imaging DEVICES FOR NUCLEAR IMAGING Radiometers are used for measuring the activity of gamma and beta radia- tions of the RP accumulated in organs and tissues before the contents of radio- active gamma and beta radiations are registered in biological tests "in vitro”. Radiographs (gamma-chronographs) are applied for non-stop registering the dependence of RP activity upon the time for characterizing the organs! functional peculiarities being investigated. Gamma-topographs: gamma-cameras, single-photon emission computer tomographs (SPECT) are used for registering the two-dimension nature of RP distribution; they are meant for the investigation of the spatial characteristics of RP in a patient's organism and obtaining organs' two-dimensional planar im- ages. Positron emission computer tomographs (PET). Any device for nuclear imaging is comprised of a detector, analyzer and reg- istration block. Registration of information can be performed in different ways: 1) measuring the absolute or average number of impulses (in radiometers); 2) drawing curves “activity-hour” (on radiographs); 3) finding out an RP displacement speed; 4) obtaining the image of the RP gamma-radiation distribution in the stud- ied organ (on scanners, gamma-tomographs, SPECT, PET); 5) the interaction of stable and tagged compounds (a radioimmunoassay “in vitro” — RIA). METHODS OF NUCLEAR IMAGING Methods of nuclear imaging are divided into 2 groups: research in the whole organism (in vivo) and biological substances (in vitro). 99Nuclear imaging in the whole organism (in vivo) Nuclear imaging in the whole organism (in vivo) is performed in case ob- taining data on the function and morphology of the system or organ being investigated are necessary. Contraindications for nuclear imaging are absent, though some limitations exist: pregnancy, the period of lactation, the age of infancy/childhood, urgent states. Depending on the purpose of a nuclear imaging of the whole organism, Nlis applied in the static (diagnostics of pathological processes of organs and systems and the study of internal organs topography) and dynamic regimes (the study of the system or organ function disturbance in the dynamics of the pathological process course). Scintigraphy Scintigraphy is performed with the help of a gamma-camera. A gamma- camera (Fig. 7.3) is a radiodiagnostic device the base of whichis a large immobile detector — monocrystal of calium iodide with the diameter of 40-60 cm with a photoelectronic multiplier (PEM) placed on it which transform light flashes on the whole monocrystal surface into electric impulses and transmit them on the computer. The processed information is passed on the screen of the monitor or paper as the image of a RP distribution in an organ (endpaper — Fig. 1). The advantage of a gamma-camera over a scanner is that gamma-cameras enable to get the information on RP distribution in the whole organ (the visu- alization of an organ or tumor) and study transient processes (blood circulation in an organ, the arterial, parenchymatous and venous phases of blood circula- tion of organs, tissues, tumors). After medical-functional prescriptions they distinguish planar gamma- cameras, single-photon emission computer tomographs (SPECT) and two-pho- ton emission computer tomographs (PET — positron emission tomographs) which enable to obtain a layerwise scintigraphic image. Radionuclide computed tomography Radionuclide computed tomography is performed with the help of single- photon emission computed tomography and two-photon positron emission tomography. 100Fig. 7.3. A planar gamma-camera MB-9200 a) the apparatus outward oppearance (1 — the radiation detector, 2 — the sup- port); b) the control panel) the scheme of the gamma-camera detector: 1 — the collimator; 2— the scintillation detector; 3 — the optic fibre 4.— the electronic scheme; 5 — lead protection, PEM — photoelectron multipliers Single-photon emission computed tomography (SPECT) is a variety of a gamma-camera in which one or several detectors of the tomograph are ro- tating around the patient's body during examination. Further, with the help of special programs the reconstruction of the RP distribution section is performed. For performing tomography they use RP that radiate gamma quanta. SPECT has a high separating capacity as compared to planar scintigraphy in revealing tiny neoplasms. The outward appearance of the single-photon emission com- puter tomograph — Fig. 7.4. Positron emission tomography (PET) is a method of studying of the organ- ism tissues functional state with the help of radionuclides radiating positrons. A positron interacts with an electron, which triggers annihilation the both particles disappear and there appear two gamma quanta moving in diametri- cally opposite directions. In a positron tomograph detectors are installed at the level of the studied patient's body part which are located one opposite another 101Fig. 7.4. The SPECT apparatus outward appearance and are moving in a circle. Simultaneous registration of two gamma quanta which emerged in the course of annihilation enables to find out the annihila- tion localization. The obtained information on the localization of a positron and an electron enables to draw a layerwise image of the studied organ with the help of com- puter (endpaper — Fig. 2). The key PET diagram — Fig. 7.5. The outward ap- pearance of PET — Fig. 7.6. A detector Annihilation A detector gamma rays ys ‘The system of data registration 102 ‘The analysis of ‘The system signals coincidence of data T registration A computer 2 Fig. 7.5. The scheme of two-photon emission positron tomographFig. 7.6. The PET outward appearance The main technical characteristics of positron tomographs are high sensitiv- ity and high resolving capacity. PET can work in 3 regimes: dynamic, static and that of the whole body study. They use ultrashort-lived radionuclides radiating positrons for PET. Ultrashort-lived radionuclides are obtained in a medical cyclotron — "90 (T,,, — 2.04 minutes), ?N (T,,, — 10 minutes), "C (T,,, — 20.1 minutes), “°F (T,,, —109 minutes). As the period of ultrashort-lived radionuclides half- decay is short, they can only be used at the site of obtaining. That is why, for full value PET research, there must be built a PET-centre comprising a medical cyclotron, a communication system and a PET-camera. Nuclear imaging “in vitro” Radioimmunoassay For finding out the biological tests radioactivity they use scintillating detec- ‘tors — well counters. The key diagram of a well counter — Fig. 7.7. Finding out the activity of radioactive tests. A vial with a test is placed in the camera of a well counter. Radiations of a ra- dioactive probe while getting to a scintillator cause flashes of light in it which, with the help of PEM, are transformed into the current of electric impulses which are passed to a registering device. 103‘| Nal PEM GA_ IZ Fig. 7.7. The key diagram of a well counter: 1 — the test tube; 2 — the radioactive test; 3 — the lead collimator; the Nai-scintillator; PEM — photoelectron multiplier Results are obtained as a numeric value in Bg of the probe when study- ing. Nuclear imaging of blood, urine, saliva, feces, spinal, ascytic and pleural flu- ids is performed in a vial, which excludes completely radiation impact on the organism of the studied patient. Radioimmunoassay (RIA) is based on concurrent linking stable and analo- gous by chemical and biological properties tagged substances with specific bonding systems after the type of "antigen - antibody” reaction. That is why such investigations got the name of radioimmune. The scheme of RIA — Fig. 7.8. If they use tagged antibodies for RIA, such an investigation is called immu- noradiometric assay (IRMA), and if the linking system is used by tissue recep- tors, such an investigation is called radioreceptor. In most standard sets for RIA they use "I (T,,, — 60 days and nights, the en- ergy of gamma rays — 35 keV). Because of the low energy of radiation the treat of the personnel's external irradiation is very small. The basic clinical indications for performing a radionuclide assay: + endocrinology — for the diagnosis of diabetes mellitus, pathology of hypothalamic-pituitary-adrenal and thyroid (the thyroid and parathy- roid glands) systems; + oncology — for the early diagnosis of benign hyperplasias (screening and selection of “risk” groups) and control over the effectiveness of treatment (monitoring patients in dynamics); 104‘The substance being investigated A tagged analog Bez Thecanals tage Aspecificaly ae perceiving System - x “Bound radioactivity” (the substances which reacted) Sa “Pree radioactivity it) §S (ihesubstances hich eb] cidnot react) A standard A test Concentration Activity Fig. 7.8. The scheme of radioimmunoassay + urology — for early diagnosis of benign hyperplasia and malignant tumors of the prostate; + cardiology — for the diagnosis of myocardial infarction and differen- tiation of vascular disturbances forms; + pediatry — for finding out factors of children and teenagers' growth disturbances; + obstetrics and gynecology — for the control over a fetus develop- ment, diagnosis of gynecological diseases and finding out reasons of infertility; alletgology — for finding out the concentration of immunoglobulins and allergens; psychiatry — for monitoring the evaluation of psychiatric disturbanc- es treatment; pharmacology — for measuring the medicine substances decay and excreting pace; hematology — for the early differential diagnosis of leukoses and ma- lignant lymphoms. . . 105NUCLEAR IMAGING IN ONCOLOGY The basic indications for nuclear imaging in oncology: + the diagnosis of primary malignant tumors and peculiarities of their growth (topic diagnosis); + searching for and diagnosing regional and remote metastases; + differentiatial diagnosis of inflammatory, benign and malignant path- ological processes; + the evaluation of treatment effectiveness, a need of treatment tactics correction in dynamics. RP for tumor diagnostics Tumor diagnosis is based on the difference between absorbing RP by a tumor and that by surrounding tussues. In some tumors tumorotropic RP accumulate in a greater number than in healthy tissues, that is why after introducing such RP a tu- mor is revealed as the focus of increased radioactivity (the “hot” zone). In other cases the tumor loses the property of accumulating RP, whereas healthy tissues surrounding the tumor absorb RP actively. That is why the tu- mor is visualized as a pprtion of the absence of RP accumulation or decreased fixation (the “cold” zone). The classification of RP for tumor diagnostics: Organotropic RP. Depending on its chemical and biological properties, the RP accumulates in certain organs (Table 7.2), Tumorotropic RP accumulate in malignant tumor cells. Bringing RP up to the tumoris also possible with the help of tagged antibodies. Scintigraphy with tagged monoclonal antibodies is called immunoscintigraphy. The requirements for tumortropic RP (TRP) 1. A high degree of tropicity and specificity to malignant tumors (the ac- cumulation of TRP in tumors must be 3-4 times as greater as that in healthy tissues). 2. The TRP must not create tsignificant irradiation of a patient's organism. 3. The TRP must be non-toxic in the chemical form of its use. The basic tumor RP — Table 7.3. 106Table 7.2. The basic organotropic RP RP Ty,» | Theperiod of | Thetropicorgan | The way of days and | investigation, introduction nights hours NaI 8&1 24 The thyroid gland per os %"Tc-pertechnetate 0.25 1 The thyroid gland WV »**Au-colloid 27 1 The liver Vv %Te-colloid 0.25 1 The liver Vv ¥7Hg-promeran 27 1 The kidneys Vv *Te-DMCA 0.25 i The kidneys Vv Te MAA 0.25 1 The lungs Vv Table 7.3. The basic tumor RP RP T,,» | The period of | The tumor localization | The way of days and | investigation, introduction nights hours P-sodium 14 | 4,24, 48,72 | Superficial tumors of per os phosphate the skin, mucous mem- branes Te MIBI 0.25 q The thyroid gland, soft, Vv tissues, the brain *Tc-pertechnetate| 0.25 05-1 The thyroid gland, soft Vv tissues, the brain Ga-citrate 3.25 24-96 | The pharynx, larynx, Vv oral cavity, lymph nodes etc-tetrofosmin | 0.25 os The mammary gland Vv sr-chloride 65 _| 24,48, 72,96 | Bone tissue Vv “eTc-pyrophosphate| 0.25 34 Bone tissue Vv 25). MIBG 60 1 The adrenal glands Vv *Se-methionine 120 12 The pharynx, larynx, Vv lymph nodes 4111n-bleomycin 28 24 All the localizations Vv *Tc-depreotide 0.25 4 The lungs Vv 107Methods of nuclear imaging in oncology in vitro” Immunoradiometric assay (IRMA) in oncology One of the ways of malignant tumors early diagnosis (before their clinic signs appear) is finding out the tumor markers level. Tumor (onco)markers are the products of tumors or organism vital activity the level of which increases in the biological fluid of the organism in malignant tumors of various localizations. None of more than 200 known markers is spe- cific to a certain tumor. Oncomarkers are divided into three groups according to: + biological function: oncofetal antigens (a chorionic antigen, a carcinoembryonic antigen, CA 15-3, CA 125 and others); hormones (adrenocorticotropic hormone, parathormone, calcitonin and others); receptors (estrogenic, progesterone); enzymes (lactatdehydrogenase, a specific antigen to the prostate and others); other compounds (fer- ritin, immunoglobulin); chemical structure: proteins, glycoproteins, glycolipids, polyamines, immunoglobulins, polypeptides, carbohydrate determinants of glyco- proteins and others); specificity and sensitivity oncomarkers are divided into: primary (with high sensitivity and specificity to certain tumors); secondary (they are less sensitive and less specific to certain tumors, but in combination with primary markers they increase significantly the probability of finding out tumors); auxiliary (specific to certain tasks, have low sensi- tivity and specificity to tumors), . The brief characteristics of oncomarkers — Table 7.4. In general, the basic stages of IRMA, according to test-instructions, are: 108 + intravenous blood sampling (the subsequent stages are implemented under laboratory conditions); * preparing the test which is to be investigated and contains a true anti- gen identical or analogical to a non-tagged standard antigen: + dissolving reagents till their complete homogeneity and incubation; + dividing into fractions — free and bound; *¢ radiometry and obtaining a numeric result of investigation; + results evaluation in terms of standard curves, giving a conclusion.Table 7.4. The characteristics of primary oncomarkers Ne | The oncomarker's The oncomarkers' level Used for malignant tumors name Norm | Border levels diagnostics 1 | CEA 8 ng/ml 8-12 ng/mL | the lungs, mammary glands, carcinoembryonic pharynx, nasopharynx, antigen organs of GIT, gallbladder, kidneys, ovaries, testicles 2 | AFP 0-5 IU/ml 5-10 1U/ml | the lungs, mammary alpha-t- glands, stomach, liver, fetoprotein ovaries 3 | HCG 0-5 IU/ml 5-10 1U/ml | the intestine, kidneys, human chorionic uterus, tumors of tropho- gonadotropin blastic and germinogenic origin 4 |CA125 0-30 1U/mI 30-40 |U/mi_ | the mammary glands, carbohydrate uterus, ovaries, metastases antigen of these tumors to the liver 5 |CA15-3 0-22 1U/ml 22-30 U/ml! | the mammary glands, carbohydrate lungs, stomach, liver, antigen pancreas, uterus 6 |CA19-9 0-301U/m! 30-40 IU/ml! | the stomach, intestine, gall- carbohydrate bladder, bile ducts, uterus, antigen, absent in metastases of these tumors men with IV (AB) to the liver blood group 7 |CA50 0-10 IU/ml 10-14 IU/ml | the lungs, esophagus, carbohydrate stomach, pancreas, liver, antigen bile ducts, uterus, metastases of these tumors to the liver 8 |CA724 0-3 ng/ml 3-6 ng/ml the lungs, esophagus, carbohydrate stomach, pancreas, liver, antigen bile ducts, uterus, metasta- ses of these tumors to the liver 9 |psa 0-Sng/ml | 5-10 ng/ml | the prostate prostate-specific antigen 109CONTROL TASKS Questions for self-control 1, Definition of the nuclear imaging. 2. Groups of nuclear imaging devices. 3. SPECT, scintigraphy — variants of results processing. 4. PET, the method's principles and advantages. 5. RIA, the method's principles and clinical significance. 6. The requirements for tumorotropic RP. 7. The main indications for nuclear imaging in oncology. 110X-RAY, CT, MRI AIND ULTRASOUND IMAGING METHODS OF X-RAY IMAGING The physical and technical basics of roentgenology A generator Of X-ray radiation is an X-ray tube — a two-electrode electro- vacuum device meant for obtaining accelerating and decelerating the elec- trons occuring around the cathode incandescent filament as a result of thermionic emission (Fig. 8.1). Wherm connecting a high-voltage tube to the electrodes in the electromagnet field occurs acceleration and swift movement of the electrons focused on the cathmode to the anode. Decelerating of elec- trons in the anode material causes tlhe emergence of quanta of electromag- netic radiation — X-rays. The more tFhe difference of potentials is brought up to the X1ay tube electrons, the mores energy electrons have and the shorter the quanta waves length of X-rays is_ (short-wave X-rays quanta have a larger energy and larger penetrability). Most of the electrons kinetic energy in the anode substance is transformed into heat energy and just around 1% — into X-rays. X-rays penetrate optically opaque media and interact with the substance which entails its uneven absorption. Fig. 8.1. An X~ray tube scheme the giass container; 2— the rotor: 3 — the anode disk; 4— the anode focal spot: 5— the cathode incandescent flarrent;6— the cathode focusing system m1The photochmical action of X-rays is at the basis of obtaining an X-ray im- age on the film whose gelatin layer contains haloid silver crystals in the form of emulsion. The X-rays property to cause fluorescence is the basis of fluoros- copy. The use of amplifying screens while performing roentgenography enables to reduce a patient's irradiation dose. The X-ray diagnostic apparatus (Fig. 8.2) is composed of an X-ray radia- tion generator (an X-ray tube), a high-voltage source, a support mechanism, an X-ray receiver and a control panel. Fig. 8.2. The digital X-ray apparatus outward appearance 1 — the X-ray tube; 2— the diaphragming system; 3 — the support mechanisin; 4 — the patient positioning table; 5 — the digital X-ray receiver Receivers are necessary for visualizing the X-rays which have passed through the object being investigated. For visualizing an image they use special fluorescent screens, cassettes with X-ray film, radiation detectors with an EOA (electro-optical amplifier) and digi- tal systems of image visualization. On the screen, in the film (after it has been photoprocessed) there appears a visible X-ray image of an object. An X-ray image is an object's model which gives the true idea of the local- ization, form, sizes, structure and, in some cases, function of human organs and systems. 2X-ray image formation On obtaining an X-ray image of the object being investigated an X-ray beam Passes through the object. According to laws ofphysics, the object's uneven density causes uneven absorption and scattering of an X-ray beam quanta part. Having passed through the object, the X-ray beam “carries” the hidden image of the studied object's structure. Disparities in absorbing X-ray radiation by organism tissues of different den- sity enables to obtain an X-ray image of the studied body surface area, Against the background of the muscles that absorb X-rays (that is have low density and, respectively, high penetrability for X-rays) there appears a distinct image of bones having high density and low penetrability for X-rays (Fig. 8.3 a, b). An X-ray image is a structural semi-transparent shade. In the place where X-ray weakening is larger, the shade has high density, that is high intensity. The shade intensity degree depends on the substance density or the thickness of a homogenous tissue through which X-ray radiation passes, Depending on the studied object's density they distinguish five degrees of media transparency: air, fatty, soft tissue, bone and metal. When passing X-ray through the patient there occurs the interaction of an X-ray quanta area with a tissue substance and there appears dissipated radiation. For removing an undesirable effect of dissipated radiation on any X-ray films they use screening grids which are deployed immediately in front of an X-ray cassette. Xray grids are built of thin lead plates places parallelly to the X-ray beam direction (narrow intervals between plates are left), At the moment of roentgenography the quanta of the X-rays that coincide with the primary beam direction penetrate freely through the grid in the film, while the dissipated radiation is absorbed by the lead plates of the grid (Fig. 8.4). Image processing Roentgenography is based on the phenomenon of photolysis of silver bro- mide into silver and bromine ions in the film photo emulsion, Particles of X-ray film' silver bromide been photolyzed, when developing are restored to metallic silver as black sediment. After washing film and its subsequent photoprocessing — fixation — there occurs the dissolving of non-photolysized haloid silver particles and its wash- ing-out into a fixation solution. After washing in water the film is dried.Fig. 8.3. An X-ray image of a normal hand and normal thoracic cavity in direct projection: 4 positive image on the fluorescent screen (a, b); a negative image on X-ray film (c, d) Fig. 8.4 The scheme of an X-ray screening grid: 1 — the table; 2— the grid; 3-—the X-ray film 4 — the investigated object; 5 5 — dissipated X-rays 114Nowadays they widely introduce the automatic chemical processing of the film with the help of developing machines. The basics of roentgenological scialogy In X-ray imaging they study a shade image which, as a consequence of op- tic and geometrical peculiarities, is presented in an unusual spatial perspective and does not always reflect the real form, size and position of the appropriate object. That is why, for the correct interpretation of an X-ray image, it is neces- sary to understand the basic laws of scialogy (the study of shade forming). At the base of an X-ray image there is put the study of the shades forming it, the evaluation of the basic scialogical properties: the form, number, size, inten- sity, structure, contours and movability. The shades of different pathological formations can merge or overlap each other and thus change the idea of their true density (Fig. 8.5). The shade's form is more often find out after images in 2-3 projections (Fig. 8.6). The shade image from depends on the peculiarities of the object or its element's spatial localization in relation to an X-ray and film (Fig. 8.7). The object's form and size change depending on the central ray direction in relation to the long axis of the object (Fig. 8.8). The object's form change is possible on obtaining not the central X-ray beam, but with the help of lateral X-rays or under the cassettes’ oblique deployment (Fig. 8.9). FE F Fig. 8.5. The investigated objects. Mutual summation: @) augmenting the image intensity; b) diminishing the image intensity Fig, 8.6. Shades forms. Geometrical figures and their shade silhouettes( ) Fig. 8.8. The dependence of the X-ray image value Sa and form on the localization of the studied object in relation to the X-ray beam directed perpendicu- Fig. 8.7. The dependence of the larly to the cassette (F — the tube's focus); X-ray image sizes on the distance a) the object's ong axis is parallel to the cassette; between the tube focus (F) and b) the abject’ long axis coincides with the X-ray the object of investigation beam direction FE FE il a: b Fig. 8.9. Change of objects’ image in roentgenography 4a) an object placed in the X-ray beam centre; b) the object's image change in roentgenography with lateral rays;¢) an object’s image change in the oblique localization of an X-rays receiver The shade's intensity reflects the degree of X-ray absorption and depends on the density and richness of the object (Fig. 8.10) The clearness of an X-ray image depends on the X-ray optic focus size and the object's remoteness from the film (Fig. 8.11). X-ray imaging of the skeleton and lungs without contrasts is possible due to their being naturally contrast, that is to the difference in the density of bones and surrounding soft tissues. The natural contrast of lungs is conditioned by certain air contents in them. 116a Fig. 8.10. A schematic image (a, b, ¢) of X-ray absorption peculiarities depending on the geometric form of the studied object » ne @, Fig. 8.11. The dependence of an X-ray image clearness on the tube optic focus size (xy) of the tube, the object ~ film and tube - film distance a Methods of X-ray imaging Methods of X-ray imaging are based on the principle of the system “the ra- diation source — the studied object — the irradiation detector” functioning. The emergence of an X-ray image is based on absorbing X-rays by studied area’ tissues of various density and registering a degree of their absorprion ona fluo- rescent screen, in an X-ray film or in physical detectors of radiation (digital im- age receivers). 7The basic methods of X-ray imaging Fluoroscopy (roentgenoscopy) — the method of transmissing an object and obtaining an image on the fluorescent screen. The method's advantage is the possibility of conducting multiaxial, polypositional investigation and studying organs’ functional state. The disadvantage is low resolution capacity in revealing subtle details of the structure of lungs and bones, the absence of objective documentation on the organs’ state at the moment of investigation and a greater X-ray load as compared to roentgenography. Roentgenography is a method of obtaining an X-ray image onan X-ray film on low-dose receivers of X-rays with the digital processing of an object. It is used for studying the morphology of the studied area. The method's advan- tage is high resolution capacity (as compared to fluoroscopy) in revealing de- tails of the structure of lungs and bones, the possibility of obtaining documen- tation on the organs’ state at the moment of investigation and a lesser X-ray load as compared to fluoroscopy. The digital technology of X-ray images visualization lies in using low-dose X-ray receivers and digital image processing (digital roentgenography). It has the following advantages — a decrease as many as 20-30 times of an X-ray load on a patient and excluding the use of an X-ray film and photolaboratory process. The key diagram of investigation with the help of a digital roentgenograhic apparatus — Fig. 8.12. | ‘The The digital plane The digital ‘The X-ray tube patient detector image | | -{ | ¢ Chasdies| | X-ray photons The digital signal Fig. 8.12. The key diagram of investigation with the help of a digital roentgenograhic apparatusSpot-film roentgenography is the method of performing X-ray image of the zone of interest with the central X-ray beam of radiation or along the tan- gent, mainly during fluoroscopy. Fluorography is the method of X-ray diagnostics in which a shade image from a fluorescent X-ray screen is filmed or transformed into a digital image with the help of low-dose filmless receivers. It is used as a method of mass pro- phylactic X-ray imaging for finding out lung diseases with a hidden course. The contraindications are: the age under 15, pregnancy. Additional methods of investigation Tomography is a method of revealing the location of anatomical structures in three-dimensional space. It is widely used in X-ray diagnostics (X-ray linear tomography, X-ray com- puted tomography) as well as in radionuclide, ultrasound diagnostics and in devices whose action is based on the magnetic resonance principle. All the tomography types pointed out are indicated for performing layer- wise organs morphological investigation (morphological tomography). Linear tomography is a method of roentgenography of some layers of the human's body for obtaining isolated image structures located in any plane on the given depth. The principle of linear tomography — Fig. 8.13. The effect of tomography is achieved due to the X-ray tube and film move- ment during shooting in mutually opposite directions, and the axis of their movement lies at the studied object’ layer, A distinct image is not only provided by those structures which are situ- ated at the level of the “tube — film” system (point O) rotation, because during the movement of tube and film they are projected on the same film's point (O,, O,, 0,). The objects above (point A) and below (point B) are projected during movement on different film's parts, that is why they are not visualized distinctly. The method's disadvantage is a higher X-ray load as compared to roentgenography. Angiography is the general name for the methods of blood vessels X-ray imaging during which vessels are filled with a contrast liquid through a special catheter (see “Interventional Radiology"), then a series of X-ray images is per- formed. Depending on which part of the vascular system is contrasted, they distin- guish arteriography, phlebography and lymphography (Fig. 8.14). 119‘The X-ray tube movement direction ‘The film movement directon Fig, 8.13. The principle of linear tomography Fig. 8.14. Angiography: a) an arteriogram of the abdominal aorta and its branches; b) a phlebogram of the femoral veins; da lymphogram of the glomerular area of the lymphatic vessels 120Angiography is performed for investigating hemodynamics, finding out vascular pathology, diagnosing diseases caused by the disturbance of vessels function and structure. Functional roentgenology is the method of performing roengenograms in different phases of organs functions (investigation of vascular permeabil- ity, lungs investigation in the phase of inspiration and expiration, investiga- tion of the articulation movements volume in flexion and extension, and others). ULTRASOUND IMAGING The physical basics of ultrasound imaging The principle of the ultrasound method of imaging visualization lies in ob- taining a focused ray of ultrasound mechanical oscillations with the frequency of 1-20 MHz, its introduction into the substance when studying through the acoustic window and registering waves reflected from different media density borders. A beam of ultrasound oscillations is introduced into the studied body’ surface area through the skin with the help of an ultrasound generator — piezoelectric transducer, The spread of ultrasound depends on a piezoelectric transducer's type, properties of an X-ray and properties of the medium through which it is pass- ing. Echogenicity is the ability of the studied structures to reflect ultrasound waves. They distinguish isoechogenous, anechogenous, hypoechogenous and hy- perechogenous structures (Fig. 8.15). The propagation of ultrasound takes place according to the laws of reflec- tion and diffraction on the border of various media, as well as the laws of dif- fraction and dissipation. The reflected waves are perceived by the same transformer, processed by an electric device and transformed in a one-dimensional or two-dimensional image (echogram or ultrasound scanogram). According to the echogram data one can define the topography, form, volume and structure of the studied organ, which enables to find out a dif- fuse or focal damage of the organ's parenchyma as well as a cavity with a fluid or air. 121Fig. 8.15. An MRI of the liver: J — the normoechogenous parenchyma of the liver; 2— the hyperechogenous capsule of the liver Ultrasound visualization modes One-dimensional visualizion modes (echography) The US A-mode (from “amplitude") is based on registering radio signals reflected from the border of media different by their density as vertical rises. Nowadays it is not used. The US M-mode (from “motion”) enables to get information on mobile struc- tures in the real time mode; it is used in heart investigation. Two-dimensional modes of visualization (sonography) The US B-mode (from “bright") is based on registering reflected impulses and their imaging on the screen as a tomographic section of tissue, their brightness being directly proportional to the ultrasound reflection intensity. It is used for tissues and organs visualization on the basis of a density gradient: water, blood, fatty tissue, parenchyma, vessel walls (Fig. 8.17). 3D (three-dimensional construction) mode of US — a stereo image ob- tained on the basis of the analysis of the images sequence obtained in the B-mode after given parameters (Fig. 8.19 a). 4D (four-dimensional construction) mode of US — a stereo image in the real time scale. 122Fig. 8.17. An ultrasonogram of the spleen, the B-mode Ultrasound dopplerography is based on the Doppler effect — a change of the frequency of an ultrasound signal reflected from a movable object. The frequency of the ultrasound signal reflected increases from the object ap- proaching and vice versa — decreases from the object that is removing (end- paper — Fig. 3). 123Dopplerographic modes of visualization Pulse wave (PW) — the mode enables to find out the blood movement velocity. Continuous wave (CW) — the mode of measuring high speeds. Power Doppler — energetic dopplerography used for the qualitative evalu- ation of low-speed blood flow in small capillary vessels (of the heart, kidneys, liver and others). Colour flow mapping (CFM), coloured flow angiography (CFA): colourful dop- plerography — marking with a colour the flow nature in the echogram in the zone of interest. Tissue velocity imaging — colour tissue dopplerography, colour mapping of tissues movement. Sonoelastography — the mode of simultaneous measuring the echogenici- ty and elasticity of biological tissues. Duplex sonography enables to obtain an image of vessels (anatomical infor- mation), a record of the blood flow curve in them (physiological information) and diagnose the damage of different vessels with the simultaneous evalua- tion of the blood flow in them. Ultrasound apparatuses (Fig. 8.18) allow to find out the distance to struc: tures due to measuring the time during which an ultrasound wave passes to certain structures and returns to the transformer. There are no contraindications for prescribing US. a - mo Fig. 8.18. An ultrasound apparatus 124Fig. 8,19. a) US, the 3D of the fetal face; b) a dopplerogram of the liver with the spectral Doppler curve of the normal hepatic artery Ultrasound semiotics Ultrasound investigation supposes finding out the pathological area lo- calization, sizes, form, contours, mobility, echogenicity, structure, presence of halo (a decreased echogenicity along the tumor's periphery — a sign of malig- nancy), sound conductivity (normal, increased, decreased, high) and interrela- tionship with surrounding tissues and organs (Fig. 8.20). Fig. 8.20. A liver’s ultrasonogram: 1a) the hepatic cyst; b) the hepatic hemangioma 125The advantages and disadvantages of US The advantages of US + ionizing radiation is not used; + no contraindications; harmlessness and the possibility of multiple ap- plication; * the possibility of application under any conditions with the help of mobile and portable apparatuses; + the high resolution capacity of soft tissues visualization; + investigation is performed in the real time mode; + the method enables to conduct intracavitary and intraoperative in- vestigation with the help of special detectors which are introduced immediately in cavities (for example, transesophageally, transrec- tally, transvaginally, etc.). Special detectors built in endoscopes en- able to carry out laparoscopic, intravascular, ultrasound investiga- tions. The disadvantages of US + the weakening of a signal with the enlargement of tissues thickness (the weakening of ultrasound penetration); + an US-signal does not penetrate bone tissue; + the gas in the lungs and cavities reflects acoustic waves and prevents from organs visualiziation; + dependence of investigation result on a patient's being prepared for investigation and an operator's qualification. X-RAY COMPUTED TOMOGRAPHY (CT) X-ray computed tomography (CT) is the method based on measuring the degree of a narrow X-ray beam weakening at the exit from the thin layer of the object being investigated. The value of weakening is proportional to tissues density which is on the way of a narrow beam of an X-ray and depends on the object's thick- ness. 126The physical and technical basics of CT Investigation is performed with the help of a computer tomograph com- prised of an X-ray tube with the system of slot collimators and detectors con- tained in the ring-gantry, table for scanning, console of the apparatus mode control, monitor and computer. In the computer there are accumulated and processed signals coming from detectors; there occurs the digital reconstruction of an image, the information saved is transmitted to the console of diagnostics and apparatus control The method was introduced by A. Kormak (1963) who suggested the mathe- matical reconstruction of a layerwise brain image. H. Hounsfield constructed the first clinical model of a computer tomograph for investigating the brain. For this research invention they were awarded the Nobel Prize in 1979. Over the time there was constructed a computer tomograph for investigating the whole human body. The thickness of the beam and, respectively, that of the layer whichis distin guished in the object can be changed from 1 to 10mm. Unlike usual roentgenography and tomography, they use detectors as crys- tals (sodium iodide and others) or ionizing gas chambers (xenon) instead of a film. Detectors perceive the difference in structures less than 1%, while in an X-ray film one can discern the density difference of 10-15 %. That is why the detector's capacity to perceive the weakening of X-ray radiation exceeds the diagnostic capacities of roentgenography 100 times. The scheme of an X-ray computer tomograph — Fig. 8.21 a The X-ray tube Thedetector Gentry Pic. 8.21. The scheme ofan X-ray computer tomograph (a) and the scheme of spiral scanning (b): 1 — the direction of the patient's moving; 2— the beginning and direction of spiral scanning; 3 — the way of the non-stop rotation of the X-ray tube and detectors in relation to the studied object 127An X-ray tube and detectors of tomographs create a system which is mov- ing in a circle and spiral in relation to the studied object. A beam of X-rays as a result of the tube's rotation on 180 or 360 degrees finds itself every time in new areas of the studied layer and, achieving detectors, causes an electric sig- nal. The greater the intensity of the X-ray quanta getting to the detectors, the more powerful electric signal they send to the computer. For identifying the areas of the studied object, the layer which is singled out during tomography is regarded as a sum of the same volumes (voxels), Every voxel has a certain projection on the computer matrix where there are registered the numeric val- ues of the X-ray weakening degree (a CT-number calculated after the force of electric signals). The planar projection of voxels is called pixels, a sum of which shapes a visual image. As in an X-ray image, those areas which have a consider- ably weakened X-ray would be light (bones, areas of calcification) while those areas which have not considerably weakened X-ray radiation (the air, fatty tis- sue) would be dark. In an X-ray image a human eye discerns just 16 grades of grey, in CT over 1000 of them are differentiated. The value of weakening corresponding to the density of tissue is calculated after the Hounsfield scale. The scale's grading depends on a tomograph's generation. The density of water is taken for a zero (0) value, the air -1000, and a bone +1000 of Houns- field units (HU). Fatty tissue has the density of about -100 HU, while parenchy- matous organs and soft tissues — from +40 to +80 HU. The outward appearance of an X-ray computer tomograph — Fig. 8.22. Fig, 8.22. The outward appearance of an X-ray computer (1 — the ring-gantry, 2— patient positioning table, 3 — the laser printer of dry thermoprinting, 4 — the monitor) 128The number of sections and their thickness are chosen depending on a di- agnosis task. Thinner sections give a greater resolution spatial capacity and, re- spectively, enable to conduct a more detailed analysis and the reconstruction of an image in other projections. Still any investigation of a certain body surface area with the help of thin sections (1-2 mm) requires more time than that with the help of thick ones (8-10 mm), which brings about a great radiation load. In the account per one section radiation load makes 0.013 Gy. That is why in every specific case they choose a compromise solution. In some cases for obtaining necessary information on the nature of a patho- logical process they apply intravenous contrasting which got the name of im- age intensification. This is conditioned by the fact that some pathological for- mations have the same density as normal tissues, so they are isodensive. During intravenous bolus contrasting they accumulate a greater amount of the contrastive substance than neigbouring tissues and become hyperdensive. Spiral CT. Spiral scanning lies in simultaneous non-stop rotating of an X-ray tube around a patient's body and in non-stop advancing movement of a table with the patient along the scanning axis through the gantry aperture. Thus, the path of the X-ray tube’s movement in relation to the direction of the table with the patient movement, has spiral shape (Fig. 8.21). Multi-detector CT differs from spiral CT by having two and more (4-, 8-, 16-, 32-, 64-, 128-, 256-, 320-, 640-) rows of detectors, some apparatuses models having two X-ray tubes. During scanning X-radiation is perceived by all the detectors at once. Using 256- and more sectional CT they obtain images technically in the real time mode with simultaneous scanning of a considerable body's part. The advantages and disadvantages of CT The advantages of CT: # no superposition of the structures located at different depth; + obtaining an image in the axial plane is provided, which enables to perform a 3D construction and virtual endoscopy (bronchoscopy, colonoscopy) and angiography; + a higher degree of tissue contrast is ensured as compared to roent- genoscopy; * obtaining quantitative information is allowed on sizes, density of some organs and tissues and pathological formations as well as finding out 129the relationship between a pathological formation and surrounding tissues; + performing contrast amplification is possible, which enables to obtain a three-phase intensified image of parenchymatous organs in the ar- terial, venous and parenchymatous phases; The disadvantages of CT: + in performing CT and SCT the effective dose of irradiation exceeds ten times the dose obtained by a patient in performing routine roentgenography, which limits performing investigation for the preg- nant and children; + the presence of artifacts from foreign bodies with high density (metal, barium sulphate); + the presence of artefacts conditioned by patient's movement, respira- tory movements, peristalsis, heart and vessels pulsation. The indications for CT + diagnosing pathologies of the brain, lungs, mediastinum, abdominal cavity, pelvis, retroperitoneal cavity, musculoskeletal system, etc.; + in oncology, for finding out a stage of malignant tumors and control- ling the effectiveness of chemotherapy; + in traumatology, for diagnosing damages in polytraumas; + performing virtual endoscopy; + restorative angiography. The general CT-semiotics CT enables: + to find out the localization of a pathological area; + to find out the number, form, contours of pathological areas; + to find out the sizes of organs and pathological areas; + to find out the structure of a pathological area; + to find out the density of organs and pathological areas in Hounsfield units; + to evaluate a change in the density of organs and pathological areas in Hounsfield units in contrasting in the arterial, parenchymatous and venous phases; 130+ to evaluate changes in surrounding tissues and organs (compression, dislocation, infiltration, etc.); + to evaluate the state of the regional lymph nodes. Images of the thoracic cavity organs obtained in roentgenography, linear tomography, CT and MDCT — Fig. 8.23. Fig. 8.23. a) a chest X-ray image in direct projection: a ring-shaped shade of a pneumocyst in the 6" segment of the right lung; b) a linear tomogram of the chest in direct projection of the same patient, a distinct image of a pneumnocyst in the 6" segment of the right lung; a computer tomogram of the normal chest in the axial projection at the level of the pulmonary artery; d) MDCT, 3D-restoration image of heart and vessels 131MULTI-MODAL IMAGES Multimodal images — the technology of combining anatomical and func- tional images. Nowadays there are developing two directions of obtaining multi-modal images. The first direction is based on multi-modal systems which unite in them- selves various diagnostic apparatuses: PET/CT, SPECT/CT, PET/MRI (Fig. 8.24). The second direction is obtaining multi-modal images from the data obtained earlier during separately performed investigations. This way is not limited by the diagnostic equipment construction, it enables to use an image from pre- liminarily obtained archives and allows to combine all the possible by now technologies of visualization: CT, MRI, SPECT, PET. Fig. 8.24. The diagnostic apparatus PET/CT outward appearance INTERVENTIONAL RADIOLOGY Interventional radiology (X-ray surgery) includes two little traumatic opera- tions performed under the control of and with the use of methods of diagnos- tic imaging — ultrasound, fluoroscopy, computed tomography (CT). After interventional radiology appeared it became far easier to find the damaged area and reveal clearly its borders during the operation. The first stage of interventional radiology is diagnostic imaging for finding out the nature and volume of damage. At the second stage they perform medi- cal manipulations. 132Interventional radiology includes the following procedures: endovascular (Fig. 8.25); endobiliary; endoesophageal; + endourinary; endobronchial; aspiration biopsy; percutaneous drainage of cysts and abscesses; percutaneous operations on different organs and systems. eae we oe ae ee aq52> Oe Fig. 8.25.A stent A stent in the coronary artery: a} coronary angiogram (the site of the stent is pointed out with the arrow); b) a schematic image of the stent in the vessel lumen All the manipulations are more often performed percutaneously with the help of special instruments. By their effectiveness these interventions are not exceeded by traditional surgical ones. After an operation performed by the method of interventional radiology they lose less blood and recover quicker. Interventional radiology often applies special contrast agents for obtaining an X-ray image of organs which do not possess natural contrast. Depending gb