Magnetic Resonance Spectroscopy

By: Fahrenheit
Consultant: dr. Ali Imran, Sp.Rad
 Abstract: MRS complements MRI as a non- invasive means for the
characterization of tissue.
MRI  signal from hydrogen protons to form anatomic images,
MRS  determine the concentration of brain metabolites NAA, Cho, Cr and
lactate in the tissue examined.
Clinical application of MRS  central nervous system disorders.
 MRS can be very helpful in diagnosing certain entities
 MRS can theoretically be performed in almost any tissue of the
human body, the brain has been the major organ of interest for
clinical MRS studies
 This is due to the rather homogeneous tissue structure of the brain,
its easy accessibility to MRS, and limited motion artifacts
MRS TECHNIQUE AND OTHER CONSIDERATIONS

 MRS : nuclei such as carbon (13C), nitrogen (15N), fluorine (19F),

and sodium (23Na), only the nuclei phosphorus (31P) and hydrogen
(1H).
 Proton (1H) >> become popular
 high natural abundance of protons
 high absolute sensitivity to magnetic manipulation
 better spatial resolution, and relative simplicity of technique
 MRS is similar to MRI performe. MRS has a few steps before the data
acquisition
 1st step  ensuring the homogeneity of the magnetic field
 Concentration of water exceeds the concentration of metabolites of
interest by a factor of 10,000/more
 Commonly used spectroscopic techniques include the SVS, with a
spatial resolution in the order of one to eight cm3, and the multi voxel
technique, also called ‘‘chemical shift imaging’’ (CSI) or MRSI,
allowing the derivation of metabolite maps
 The two-dimensional CSI (2D-CSI or MRSI) technique requires
longer acquisition and post-processing times.
 techniques for 3D MRSI allow spectral maps and metabolite images
to be obtained from a large volume of the brain
 The selection of appropriate MRS techniques, including measurement parameters
such as repetition time (TR) and echo time (TE), depends on the clinical question.
 Short TE (20 to 35 ms) evaluations are required when there is need for detection
of metabolites with short relaxation times, such as glutamine, glutamate, myo-
inositol, and certain amino acids. Long TE studies (135 to 270 msec) are
sufficient for the detection of the major metabolites such as N-acetyl aspartate
(NAA), choline (Cho), creatine (Cr), and lactate/lipids (LL)
 several limitations to MRS : difficult to perform MRS in or adjacent
to tissue with high differences in magnetic susceptibility compared
with brain tissue, such as bone, air, fat, and hemorrhage
 The amplitude of the metabolite resonances (peaks) differs depending on the TE,
the TR, and the localization sequence. SVS automatically generates values for the
signal intensity for a few of the metabolite resonances. In contrast, when 2D-CSI
MRS is performed, further post processing is required to obtain the signal
intensity values, quantity the metabolite concentrations, and calculate the various
metabolite ratios
 These calculations : by using automated calculation programs such as the linear
combination model method (LC-model) or Magnetic Resonance User Interface
(MRUI)
MAJOR METABOLITES AND THEIR SIGNIFICANCE

 The results of MRS are displayed as a spectrum of resonances

(peaks) distributed along the x-axis, labeled in parts per million
(ppm). The amplitude of the resonances is measured on the y-axis
using an arbitrary scale.
 In brain MRS, the resonances of interest are NAA, Cho, Cr, mI,
Lac, Lip, gln and glu, & amino acids
 FIG. 1. Normal magnetic resonance spectroscopy (MRS) spectrum using a long
TE (270 ms) shows the major peaks of Cho, Cr, and NAA.
 FIG. 2. A. MRS scout image shows the measurement area (rectangle) for single
voxel spectroscopy over the region of the left basal ganglia. B. MRS spectrum using
an intermediate TE (TE = 144 ms) shows inversion of the lactate doublet (Lac) at
1.33 ppm. The high Cho is a normal finding in infant brains undergoing active
myelination
NORMAL VARIATIONS IN METABOLITE
CONCENTRATIONS

 There are age-related and regional variations in the concentrations of various

metabolites in the brain.
 The age- related variations are more noticeable in the first years of life and
mainly reflect myelination
 increase in the NAA/Cr ratio which peaks at 10–14 years, being higher in
children than in normal adults and then reducing in the elderly
 Regional variations of metabolite concentrations in the brain are seen between
gray and white matter (NAA is higher in white matter and Cr and Cho are higher
in gray matter)
 Between the different parts of the brain (cerebrum and cerebellum, frontal and
occipital lobes)
CLINICAL APPLICATIONS OF MRS

 Although MR spectra can be read visually, quantitative data and

metabolite ratios are required for a precise interpretation
 MRS spectra should always be read in conjunction with the
morphologic information derived from MRI or CT studies
Neoplasia

 MRSI allows the inclusion of surrounding normal brain which may yield
information related to the extent of the lesion and infiltration into surrounding
parenchyma that appears normal on MRI
In astrocytomas
 MRS : ↑ Cho a high cellularity and/or cell turnover
↓ NAA normal neurons are replaced or destroyed by the
mass Lactate present  high glycolytic rates and
also lipids due to cellular breakdown and necrosis.
 ↓ NAA and ↑ Cho and Cho/Cr ratios  higher WHO tumor grade
 FIG. 3. Astrocytoma. A. Axial FLAIR image shows a right periinsular mass. B. MRS scout image
shows the measurement area (large rectangle) and multiple voxels (small numbered rectangles)
corresponding to the spectra in C. C. MRS spectra show an increase in Cho and a reduction in NAA
in different areas of the lesion
 FIG. 4. High-grade astrocytoma. A. MRS scout image. B. MRS spectrum of the necrotic
center of the lesion shows a non- specific increase in lactate and lipids. C. MRS spectrum of
the anterior rim of the lesion shows an increase in Cho, a lipid- lactate peak, and almost
complete absence of the NAA peak. D. MRS spectrum of the adjacent white matter shows a
marked decrease in NAA, suggesting tumor infiltration.
MRSI :
heterogeneous lesions with areas of proliferating tumor & necrosis,
cysts, hemorrhage or edema, and adjacent normal-appearing brain
tissue. Proton MRS cannot supplant biopsy but may be of help in
guiding brain biopsy
MRSI possible to separate infiltrative tumors from circumscribed lesions such as
metastases.
 Infiltrative processes such as high grade astrocytomas demonstrate abnormal
NAA/Cho ratios not only in the contrast-enhancing portions of the tumor, but also
in the surrounding brain tissue, perhaps a sign of tumor infiltration.
 In contrast, metastases and other circumscribed lesions such as abscesses or
meningiomas do not show severely abnormal NAA/Cho ratios outside the lesion
(Fig. 5).
 The area of vasogenic edema surrounding focal lesions may yield a ↓ in
NAA/Cho ratio but without a significant ↑ in Cho/Cr. The area adjacent to an
encapsulated abscess may show ↑ lactate and ↓ NAA.
 Extra-axial tumors, such as meningiomas and metastases, usually displace
neuronal tissue and hence show very low levels or absence of NAA
 Like other tumors, meningiomas and metastases show increased Cho levels.
Meningiomas may show the presence of alanine
 A reported case has shown an elevated resonance at 2.05 ppm of an unidentified
compound, which is not NAA, in a cystic metastasis from mucinous
adenocarcinoma (Fig. 5)
 FIG. 5. Metastatic adenocarcinoma. A. MRS scout image shows measurement area
(large rectangle) and voxel (small rectangle) corresponding to the spectrum in B. B. MR
spectrum of the central cystic portion of the lesion shows a non-specific increase in
lactate. C. MRS spectrum at the lesion border shows a peak at 2.05 ppm along with the
Cho, Cr, and lipid-lactate peaks. D. MRS spectrum of the adjacent white matter is
normal. Compare to the MRS spectrum of the infiltrating astrocytoma in Figure 4
 New contrast-enhancing lesions that appear at the site of a previously identified
and treated primary intracranial neoplasm present a significant diagnostic
dilemma. MRS may be useful in the differentiation of tumor recurrence from
radiation necrosis. Radiation changes include ↓ NAA, Cho, and Cr resonances
compared with normal brain tissue.
 2D-CSI spectroscopy has been shown to be able to differentiate recurrent tumor
from radiation injury, demonstrating significantly higher Cho/NAA and Cho/Cr
ratios in recurrent tumor compared with radiation injury and normal-appearing
white matter
 In a study evaluating patients with lung cancer who had received
whole brain radiation therapy, MRS detected a decline in the whole
brain NAA even when MMSE scores were unchanged, suggesting
that MRS may be a more sensitive measure of radiation injury
Multiple Sclerosis

 Acute MS lesions show an initial reduction in NAA

 Contrast-enhancing lesions also are likely to show ↑ Cho and lipids, which are
myelin breakdown products. Chronic MS lesions show ↓ NAA, particularly in
T1 hypointense lesions, which may also show ↑ myo-inositol, possibly
indicating gliosis
 recent MRS studies indicate that normal-appearing white matter on MRI may
display regional ↑ in choline and lipids. ↓ in NAA in the normal-appearing
white matter may provide a better correlation with functional impairment than the
number of T2 hyperintense lesions. Thus, MRS may be used for detection of
axonal damage and demyelination in MS
Systemic Lupus Erythematosus

 using SVS, have demonstrated a ↓ in NAA/Cr and an ↑ in Cho/Cr in the white

matter and basal ganglia of NP-SLE patients as compared with those of normal
healthy volunteers
 In a study of acute NP-SLE patients, 2D-CSI MRS demonstrated significantly
lower NAA/Cho, and significantly ↑ Cho/Cr & LL/Cr ratios as compared with
normal volunteers. Further ↓ in NAA/Cho and NAA/Cr ratios at a three month
follow-up visit supported the assumption that neuronal damage, seen as a decline
in NAA, might be irreversible even if the SLE patient receives appropriate
treatment
Acute Disseminated Encephalomyelitis (ADEM)

 ↑ lactate was detected in lesions of ADEM. Low levels of NAA on

initial MRS were reported in a case of ADEM with multiple
transient brain lesions on MRI. At final follow-up, neurologic
examination and brain MRI findings and NAA levels had all
recovered to normal. In contrast to other demyelinating diseases
such as MS or leukodystrophy, choline levels were normal
HIV/AIDS

 Spectroscopic abnormalities have been observed in neurologically

normal HIV patients or those with normal MRI results. ↑ in choline
and myo-inositol are seen in virtually all cases of HIV infection,
even in the early asymptomatic cases. Neurologically asymptomatic
HIV patients have minimal / no change in NAA or NAA/Cr, but
HIV dementia is associated with a decrease of NAA and NAA/Cr
 Progressive Multifocal Leukoencephalopathy (PML).
↑ Cho/Cr and mI/Cr, and ↓ NAA/Cr
 Toxoplasmosis vs Primary CNS Lymphoma
Similar ↑ in lipid and lactate to that seen in toxoplasmosis may
also be seen in necrotic portions of lymphoma & other tumors, but
solid tumor in lymphoma shows ↑ Cho levels
Brain Abscess

 Another use of proton MRS is in the non-invasive differentiation of brain abscess

from other cystic lesions such as necrotic tumors.
 MRS may show an absence of normal metabolites in the central cystic portion of
a medically untreated abscess, with resonances corresponding to acetate (1.9
ppm), lactate (1.3 ppm), pyruvate, and succinate (2.4 ppm) (end products of
microbial metabolism), amino acids such as valine, leucine, and isoleucine (0.9
ppm) (end products of the action of proteolytic enzymes), alanine (1.5 ppm), and
lipids (0.9–1.3 ppm)
 FIG. 6. Brain abscess. A. MRS scout image shows measurement area (large
rectangle) and voxel (small rectangle) corresponding to the spectrum in B. B. MRS
spectrum showing prominent resonances in the 0.9 to 1.5 ppm range, and peaks at 2 and
2.4 ppm in a pattern suggesting a bacterial brain abscess
 Metabolic Disorders

traditionally SVS has been the more commonly used technique in the evaluation of
metabolic disorders.

Mitochondrial disorders
 including Leigh disease, Kearns-Sayre syndrome, mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and
myoclonic epilepsy with ragged red fibers (MERRF)
 anaerobic glycolysis & the accumulation of lactate in the brain (Fig. 7). MRS can
demonstrate the presence of lactate in normal-appearing brain tissue
 Metabolic Disorders

Peroxisomal disorders
 include the various forms of X-linked adrenoleukodystrophy (x-linked ALD),
neonatal ALD, and Zellweger syndrome.
 the MRS findings of reduction in the concentrations of NAA and glutamate (Glx) are
consistent with neuronal damage or loss, and increased Cho levels indicate active
demyelination
 FIG. 7. Mitochondrial disease. A. Axial T2-weighted MRI shows high signal in the
white matter of this 4 month old child. B. MRS scout image shows localization for
single voxel spectroscopy in the right parietal white matter. C. MRS spectrum at TE = 35
milliseconds shows a upright lactate doublet at 1.33 ppm. D. MRS spectrum at TE = 144
milliseconds shows an inverted lactate doublet at 1.33 ppm
Lysosomal disorders include conditions such as meta- chromatic leukodystrophy, Krabbe
disease, Niemann-Pick disease and mucopolysaccharidosis. In Krabbe disease, a markedly ↓
NAA and an abnormally high Cho/ NAA ratio
 Metachromatic leukodystrophy is characterized by an ↑ in mI and lactate and a decrease in
NAA

Amino acid disorders. MRS changes have been reported

In phenylketonuria, ↑ levels of phenylalanine are observed in the blood with ↑ urine levels of
phenylpyruvate
 High T2 signal white matter changes seen on MRI have been shown to regress with dietary
therapy. Resonances corresponding to phenylalanine have been demonstrated using short TE
at 7.37 ppm, in the spectral range far to the left of the other commonly evaluated
metabolites. Other metabolites are usually normal
In maple syrup urine disease, branched chain amino acids such as leucine,
isoleucine, and valine are ↑
 MRS has been shown to be positive even when MRI is negative, and the
resonance ↓ with successful treatment

Canavan disease is a disorder with a congenital defect in the metabolism of

NAA involving the enzyme aspartoacylase. This results in an ↑ in NAA levels in the
brain. Low Cho levels
Ischemia

 MRS changes include a ↓ in NAA that occurs over several days after the stroke.
NAA may pseudonormalize several weeks after the event due to brain atrophy.
Lactate rises early after the insult in the acute phase (<24 hours) and may remain
high over a long period into the chronic phase (>7 days)
Epilepsy

 Temporal lobe epilepsy can also be studied by MRS, which has shown ↓ NAA
representing neuronal loss or dys- function. Lactate may ↑ in a seizure focus,
persist for several hours, & be used as a marker for seizure activity
Neurodegenerative Disorders

 Patients with Alzheimer disease show ↓ levels of NAA along with a significant
↑ in myo-inositol. Similar changes may be seen in frontotemporal dementia
 Findings in multi-infarct dementia are non-specific with low levels of NAA; in
severe cases, lactate may be present, or myo-inositol may be ↑ indicating gliosis
Traumatic Brain Injury

 MRS has demonstrated a ↓ in NAA, a reflection of diffuse axonal injury or

metabolic depression. Concentrations of NAA predict cognitive outcome. An
initial fall and subsequent recovery of NAA in white matter
 In contrast, NAA concentration in gray matter was found to fall continuously
after trauma. ↑ of Cho is also noted early after the injury, suggesting an
inflammatory response. The ↑ in Cho in the gray matter was seen to persist,
possibly reflecting ongoing inflammation
Thank You 