ADVANCED MR IMAGING

TECHNIQUES IN
THE DIAGNOSIS AND POST-
THERAPEUTIC
FOLLOW-UP OF INTRAAXIAL BRAIN
LESIONS

VIRGIL IONESCU M.D. PhD

SANADOR CLICAL HOSPITAL - BUCHAREST
LAY-OUT

 INTRAAXIAL BRAIN LESIONS ARE A SIGNIFICANT HEALTH

PROBLEM AND PRESENT SEVERAL IMAGING CHALLENGES
 THE ROLE OF IMAGING IS NO LONGER LIMITED TO MERELY
PROVIDING ANATOMIC DETAILS
 SOPHISTICATED MAGNETIC RESONANCE (MR) IMAGING
TECHNIQUES ALLOW INSIGHT INTO SUCH PROCESSES AS THE
FREEDOM OF WATER MOLECULE MOVEMENT, THE
MICROVASCULAR INTEGRITY AND HEMODYNAMIC
CHARACTERISTICS, AND THE CHEMICAL MAKEUP OF CERTAIN
COMPOUNDS OF LESSIONS
THE ROLE OF RADIOLOGIST

 DIAGNOSIS
 IS THIS A TUMOR OR SOMETHING ELSE?
 IS THIS A BENIGN OR A MALIGNANT TUMOR?
 TREATMENT PLANING
 WHERE SHOULD BE RADIATED?
 WHICH PART SHOULD A SURGEON TAKE OUT?
 POSTTREATMENT
 NEW TUMOUR vs. TREATMENT EFFECT
LAY-OUT

 THE MOST COMMONLY USED ADVANCED MR IMAGING TECHNIQUES:

 PERFUSION IMAGING
 DIFFUSION-WEIGHTED IMAGING
 MR SPECTROSCOPY
 THE MOST COMMONLY LESIONS TO BE DIFERENTIATED INCLUDE :
 PRIMARY NEOPLASMS (HIGH- AND LOW-GRADE)
 SECONDARY (METASTATIC) NEOPLASMS
 LYMPHOMA
 TUMEFACTIVE DEMYELINATING LESIONS
 ABSCESSES
 ENCEPHALITIS
LAY-OUT
 MAPS OF
 APPARENT DIFFUSION COEFFICIENT (ADC)
 FRACTIONAL ANISOTROPY (FA)
 RELATIVE CEREBRAL BLOOD VOLUME (rCBV)
 METABOLIC ABNORMALITIES IN THE SPECTRUM
 THE PERMEABILITY MAPS AND CURVES

 ENABLE THE RADIOLOGIST TO IDENTIFY

 TUMOR TISSUE
 DIFFERENTIATE TUMOR TYPES
 GRADE TUMORS
 EVALUATE TUMOR EXTENT
 GUIDE STEREOTACTIC BIOPSY
 DETERMINE EARLY RESPONSE TO TREATMENT
Diffusion-Weighted Imaging

 DW imaging has been used to grade brain tumors on the basis of

cellularity
 Low ADC values have been correlated with
 increasing cellularity
 increasing grade
 increasing Ki-67 cellular proliferation index in cere- bral gliomas
Fractional Anisotropy

 FA represents the magnitude and directionality of water diffusion

 FA measurements may help distinguish glioblastoma multiforme
(GBM) from solitary brain metastases
Magnetic Resonance
Spectroscopy
 MRS is a noninvasive, in vivo technique that provides additional
metabolic diagnostic indices beyond anatomic information, which
has been extensively used to evaluate brain tumors

 High choline (Cho) and lipids (Lip), along with low N-

acetylaspartate (NAA) peaks, are related to tumor
aggressiveness
Dynamic Susceptibility Contrast
(Perfusion) MR Imaging
 rCBV maps can be generated from dynamic sus- ceptibility
contrast (DSC) T2* gradient-echo–echo- planar sequence (GE-
EPI), acquired during the first pass of the standard dose of a
gadolinium-based contrast agent

 Tumor blood volume (TBV) values can be measured from the

rCBV map, and TBV has been correlated with tumor grade and
vascu- larity, with higher TBV associated with gliomas of higher
grade
Dynamic Contrast-Enhanced
(Permeability) MR Imaging
 DCE studies allow estimation of brain tumor permeability, and
have been used more recently in the characterization of brain
tumors
 With pharmacokinetic modeling we can determinate parameters
such
 volume transfer constant (Ktrans)
 volume of the extravascular-extracellular space (Vee)
 blood plasma volume (Vp)
F 50y brain stem lesion
F 50y brain stem lesion
F 50y brain stem lesion
F 50y brain stem lesion
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 8y two lessions tumour vs cortical dysplasia
F 58 y glioblastoma
F 58 y glioblastoma
F 58 y glioblastoma
M 36 y Encephalitys vs gliomatosis cerebri
M 36 y Encephalitys vs gliomatosis cerebri
M 36 y Encephalitys vs gliomatosis cerebri
M 36 y Encephalitys vs gliomatosis cerebri
M 36 y Encephalitys vs gliomatosis cerebri
M 36 y Encephalitys vs gliomatosis cerebri
M 36 y Encephalitys vs gliomatosis cerebri
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
F 28 y PML – Limphomatoza – gliomatoza (imunosupresed)
DIAGNOSTIC ALGORITHM

 APPLICATIONOF A DIAGNOSTIC ALGORITHM THAT

INTEGRATES ADVANCED MR IMAGING FEATURES
WITH CONVENTIONAL MR IMAGING FINDINGS MAY
HELP THE PRACTICING RADIOLOGIST MAKE A MORE
SPECIFIC DIAGNOSIS FOR AN INTRAAXIAL LESION
 ALGORITHM FOR UNKNOWN INTRACRANIAL LESSION CLASSIFICATION
S186 October 2006 RG f Volume 26 ● Special Issue

R a d io G r a p h ic s

Figure 11. Algorithm for unknown intracranial mass classification. T his practical M R imaging algorithm is
composed of a series of nodes or questions that would suggest a diagnosis if the paths are followed to the bot-
tom. Cho choline, High GN high-grade neoplasm, Low GN low-grade neoplasm, TDL tumefactive
demyelinating lesion.
Cho choline, High GN high-grade neoplasm, Low GN low-grade neoplasm, TDL tumefactive
demyelinating lesion. Integrated Conventional T he general purpose at this point is to dis-
criminate typically nonenhancing lesions such as
* RadioGraphics 2006;and Advanced
Riyadh MR&AL
N. Al-Okaili Imaging Diag-
low-grade neoplasms and encephalitis from typi-
Question 1: Does the Lesion Enhance at
Conventional MR Imaging?

 An assessment of whether the lesion is intraaxial or extraaxial is

crucial as an initial step
 Simple visual inspection is performed to assess for any perceived
enhancement
Question 1: Does the Lesion Enhance at
Conventional MR Imaging?

 The general purpose at this point is to discriminate typically

nonenhancing lesions such as low-grade neoplasms and
encephalitis from typically enhancing lesions such as abscesses,
lymphomas, tumefactive demyelinating lesions, high- grade
primary neoplasms, and metastatic lesions
 Contrast enhancement is not specific
 It represents disruption of the bloodbrain barrier
 It is commonly used in clinical practice as an initial discriminator
to improve lesion detection and differentiation
Question 2: Is Diffusion Facilitated, as
Determined with Diffusion-weighted
Imaging?
 At this point, the lowest ADC value (expressed 10 3 mm2/sec)
should be recorded from several regions of interest within the
lesion, including both enhancing and nonenhancing parts,
regardless of whether that part was solid or cystic
 The primary purpose is to separate lesions that typically have
reduced diffusion such as lymphomas and abscesses from lesions
that typically have facilitated diffusion such as neoplasms and
tumefactive demyelinating lesions
 There is no universally accepted threshold for ADC to determine
whether diffusion is facilitated or not (value of 1.1 10 3
mm2/sec )
Question 3: Is There Rim Enhancement or
Necrosis at Conventional Postcontrast
MR Imaging?
 Presence of necrosis is indicated by a nonenhancing area, which
is dark on T1- weighted images, bright on T2-weighted images,
and surrounded by enhancing tissue

 This question helps differentiate lymphomas, which typically lack

rim enhancement in immunocompetent patients before therapy,
from tumefactive demyelinating lesions, abscesses, and high-
grade neoplasms, in which central necrosis and peripheral
enhancement are common
Question 4: In Lesions with Facilitated
Dif- fusion, Is Perfusion Increased?
 Perfusion measurements are made from several regions of
interest within the lesion and compared with values obtained in
normal white matter.
 The highest rBV is recorded from several regions of interest,
including both enhancing and nonenhancing portions of the
lession, regardless of whether the portion is solid or cystic.
 There is no universally accepted single threshold for rBV that can
help discriminate among the various intraaxial lesions.
 Neoplastic lesions tend to have higher rBV
 In a separate study, the use of an rTBV threshold of 1.75 to
distinguish high-grade neoplasm from low-grade glial neoplasms
resulted in the lowest C2 type error and a sensitivity of 95.0%
and a specificity of 57.5% (*)
* Law M, Yang S, Wang H, et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic
imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 2003
Question 4: In Lesions with Facilitated
Dif- fusion, Is Perfusion Increased?

 The purpose here is to differentiate tumefactive demyelinating

lesions and abscesses from high-grade neoplasms and
metastases
 Primary high-grade neoplasms and metastases are expected to
have an elevated rBV (in contrast to tumefactive demyelinating
lesions, abscesses, and low-grade neoplasms) because of
differences in angiogenesis induction
Question 5: Is There Infiltration of Sur-
rounding Tissue?

 Metastases tend not to infiltrate surrounding tissue

 Spectroscopic interrogation of peritumoral tissue can be more
effective for differential diagnosis than measurements from
enhancing tissue
 There is no universal discriminating threshold for the choline/NAA
ratio
 A ratio of 1.0 was shown to have 100% accuracy for
differentiating between primary and secondary neoplasms when
correlated with results of stereotactic biopsies in one study (*)

* Burtscher IM, Skagerberg G, Geijer B, Englund E, Stahlberg F, Holtas S. Proton MR spectroscopy and preoperative diagnostic accuracy:
an evalua- tion of intracranial mass lesions characterized by stereotactic biopsy findings. AJNR Am J Neurora- diol 2000
Question 6: In Lesions with Reduced
Diffu- sion and Rim Enhancement, Is
Perfusion Increased?
 As previously indicated, neoplastic lesions tend to have higher
rBV compared with that of abscesses
 The threshold of 1.75 used in Question 4 is used at this point for
the sake of simplicity
Question 7: Is There Elevation of Choline/
NAA Ratio?
 Despite overlap of MR spectroscopic ratios for encephalitis,
tumefactive demy- elinating lesions, and gliomas, choline/NAA
ratio of 2.2 can be used to separate primary high-grade
neoplasms from mimicking lesions such as encephalitis and
tumefactive demyelinating lesions.
 This value was calculated through a meta-analysis of published
choline/ NAA ratios for high-grade gliomas, tumefactive
demyelinating lesions, and encephalitis (*,**,***, ****)
 Those cases in which the response to this question is “no” are an
imaging challenge, and clinical and imaging follow-up or a biopsy
certainly has a role for further discrimination.
* Moller-Hartmann W, Herminghaus S, Krings T, et al. Clinical application of proton magnetic reso- nance spectroscopy in the diagnosis of intracranial
mass lesions. Neuroradiology 2002
** Burtscher IM, Skagerberg G, Geijer B, Englund E, Stahlberg F, Holtas S. Proton MR spectroscopy and preoperative diagnostic accuracy: an evalua- tion
of intracranial mass lesions characterized by stereotactic biopsy findings. AJNR Am J Neurora- diol 2000
*** Chang L, Miller BL, McBride D, et al. Brain lesions in patients with AIDS: H-1 MR spec- troscopy. Radiology 1995
**** Saindane AM, Cha S, Law M, Xue X, Knopp EA, Zagzag D. Proton MR spectroscopy of tumefactive demyelinating lesions. AJNR Am J Neuroradiol 2002
Question 8: In Nonenhancing Lesions, Is
Perfusion Increased?

 The threshold of 1.75 used in Questions 4 and 6 is used at this

point in the algorithm. Perfusion imaging has better accu- racy
than MR spectroscopy and ADC for grading primary brain
neoplasms
Flowchart illustrates order of methods used to diagnose and differentiate intraaxial lessions.
Each method provides an answer to a specific question, which is used as a discriminator to distinguish lesions. 1.1/100MM2/ADC
1.1 10 3 mm2/sec,ADC apparentdiffusioncoefficient,CE contrastmaterial enhanced, Cho choline, NAA N-acetylaspartate, r/CBV
relative cerebral blood volume, TDL tume- factive demyelinating lesion.
SIMPLIFIED

 BENIGN LESIONS WILL HAVE LOWER Cho THAN MALIGNANT

 BENIGN LESIONS WILL HAVE LOWER rBV THAN MALIGNANT

 COMBINED MESUREMENT OF Cho AND rBV WILL HAVE HIGHER

SENSITIVITY/SPECIFICITY THAN EITHER ALONE
B 33 y
B 33 y
B 33 y
B 33 y
B 33 y
B 33 y
Determination of Tumor
Progression
 In patients diagnosed with LGGs, advanced MR imaging techniques may
detect malignant trans- formation earlier than conventional imaging
studies
 ADC
 During follow-up, foci of restricted diffusion related to high cellularity and
malignant transformation may be demonstrated in these lesions
 A calculated ADC ratio (tumoral ADC divided by the ADC in the contralateral
white matter) of less than 1.0 is related to malignant transformation in LGGs.

 MRS
 Malignant degeneration can be demonstrated earlier with 1H-MRS than with
cMR imaging, whereby an increased Cho/Cr or Cho/NAA is suggestive of
malignant progression
Determination of Tumor
Progression
 DSC MR imaging
 An increase in rCBV is likely to provide an early noninvasive indicator of
malignant progression and activation of the “angiogenic switch.”
 Increases in rCBV may precede the development of contrast
enhancement by at least 12 months in transforming LGGs
 It is recommended that MR perfusion imaging be used routinely in the
initial assessment and subsequent evaluation of patients with LGGs who
are treated conservatively
 DCE MR imaging
 During the follow-up of a grade II glioma, appear- ance of foci of high
permeability in the permeability study within the tumor should raise
concern for malignant transformation
F 30 y Foolow-up residual tumor LGG
F 30 y Foolow-up residual tumor LGG
F 30 y Foolow-up residual tumor LGG
F 30 y Foolow-up residual tumor LGG
Determining the Ideal Site for
Biopsy
 It is estimated that up to 25% of brain tumors are undergraded
because the most malignant portion of a neoplasm may not
enhance
 DSC MR imaging
 The area with maximum rBV value in a high-grade glial tumor will be the
best site for biopsy -
 This technique may prevent undergrading (eg, sampling error) and may
demonstrate biologic differences (eg, genetic change) in the tumor
 DCE MR imaging
 The best place for biopsy is likely the area of highest permeability, which
corresponds to the presence of leaky vessels derived from angiogenesis,
known to occur in more malignant tumors areas
Assessment of Tumor
Extension
 DSC MR imaging
 High-grade tumors tend to infiltrate the parenchyma around the
enhancing tumor nodule
 Perfusion alone or in combination with MRS imaging may better
define tumor borders than cMR imaging
Assessment of Therapeutic
Response
 Preterapeutic MRS – predictiv of treatment response
 Incresed Cho/Cr and Cho/NAA ratios are predictors of poor survival
 Lacatate/NAA above 2 = 20 % 12 mo survival rate
 Lacatate/NAA below 2 = 85 % 12 mo survival rate
M 25y butterfly glioma
M 25y butterfly glioma
M 25y butterfly glioma
M 25y butterfly glioma
M 25y butterfly glioma
M 25y butterfly glioma
M 25y butterfly glioma
M 25y butterfly glioma
IS THERE A NEED FOR ADVANCED
IMAGING IN MONITORING AND FOLLOW-
UP OF A BRAIN TUMOUR?
 Conventional MRI in tumor progression/pseudoprogression
 Clasic criteria
 enhancement
 size
 limitation
 Advanced MRI in tumor progression/pseudoprogression
 diffusion (DWI),
 perfusion (PWI)
 New analyzing methods for treatment response
 parametric response maps
 Pseudo-progression
 Pseudo-response
 Radiation injury
MRI BIOMARKERS OF RESPONSE
IN HIGH GRADE GLIOMA
 TREATMENT RESPONSE FOR CNS TUMORS USUALY IS MEASURED
WITH THE MacDonald CRITERIA 8-10 WEEKS FROM THE TIME
TREATMENT STARTED
 CHANGES IN BOTH DIFFUSION MRI AND PERFUSION MRI HAVE
BEEN PROPOSED TO FUNCTION AS EARLY METRICS OF RESPONSE
TO THERAPY
 THE BEST WAY TO ASSESS RESPONSE IN DIFFUSION AND PERFUSION
DATA HAS NOT BEEN ESTABLISHED
LIMITATION OF MacDonald
CRITERIA
 SUBSTANTIAL INTER-READER DISAGREEMENT
 NO ASSESMENT OF NONENHANCING TUMOR
 THE DIFFICULTY OF MEASURING IRREGULARLY SHAPED TUMORS
 LACK OF GUIDANCE FOR THE ASSESSMENT OF MULTIFOCAL
TUMORS
 USE ONLY CR AS A SURROGATE FOR TUMOR SIZE
IS THERE A NEED FOR ADVANCED
IMAGING IN MONITORING AND FOLLOW-
UP OF A BRAIN TUMOUR?
 If so which tehniques? And do they work?
 Perfusion
 Diffusion
 Spectroscopy
Assessment of Therapeutic Response

 An important issue in patients with brain tumors is the

differentiation between recurrent brain tumor and radiation
injury/change, particularly when new contrast-enhancing lesions
are seen in previously operated and/or irradiated regions.
 Since the introduction of combined chemoradia- tion with
temozolamide as the current standard of care for HGGs, the
phenomenon of pseudoprogres- sion (PsP) has been increasingly
recognized.
 Although the exact definition of PsP is still debated, it most often
refers to a new or increased contrast enhancement on MR
imaging within the first 3 to 6 months of chemoradiation, earlier
than occur with radiation therapy alone
Advanced MR imaging techniques and
their role in the evaluation of treated
gliomas
 ADC
 Successful radiation and/or chemotherapy will result in tumor cell
necrosis; as a result, restricted diffusion related to high cell
density will be converted to high diffusivity, characterized by
increased ADC values
 Diffusion may help to distinguish tumor recurrence from
postresection injury
 Evaluation of the immediate postsurgery MR imaging may
demonstrate restricted diffusion within the surgical margins cor-
responding to the area of enhancement in the follow-up MR
imaging, compatible with postresec- tion injury
Advanced MR imaging techniques and
their role in the evaluation of treated
gliomas
 DSC and DCE MR imaging
 In recurrent tumor, vascular proliferation results in elevated
rCBV, whereas in delayed radiation necrosis (DRN), lower rCBV is
seen because it is the result of extensive fibrinoid necrosis,
vascular dilation, and endothelial injury
 The use of DCE MR imaging to diagnose DRN is much more
limited than with the use of rCBV.
 A study of 18 patients with HGG showed that a Ktrans threshold
of greater than 0.19 produced 100% sensitivity and 83%
specificity for detecting recurrent glioma versus DRN
F 65 y glioblastoma op + temodal
F 65 y glioblastoma op + temodal
F 65 y glioblastoma op + temodal
F 65 y glioblastoma op + temodal
F 65 y glioblastoma op + temodal
F 65 y glioblastoma op + temodal
F 65 y glioblastoma op + temodal
F 40 y Tumora profunda biopsiata
F 40 y Tumora profunda biopsiata
F 40 y Tum prof biopsiata
CONCLUSIONS

 Advanced MR imaging techniques can provide additional diagnostic

indices beyond anatomic information that is typically generated with
cMR imaging

 With the introduction of DW imaging, advanced MRS, DSC MR

imaging, and DCE MR imaging studies, the neuroradiologist now has
the tools needed to exploit a body of imaging information, including
the likely histology of a lesion, cellularity, capillary density, and
meta- bolic profiles—information that is essential to understanding
tumor characteristics and to developing appropriate differential
diagnoses.
CONCLUSIONS

 Advanced MR imaging techniques may also provide prognostic

information and may be used to guide therapy early on in the
patient’s treatment, effectively improving outcomes and minimizing
side effects, both in the short and long term

 Therapeutic response to therapy may be better estimated by use of

advanced MR imaging techniques than simply through cMR imaging