3. MR SPECTROSCOPY
• Detection of frequency dependent signals from
individual metabolites
• Interpretation is based on identity of chemical
and concentration
• Baseline normal spectra - constant
• Concentration of each metabolites alter in a
reproducible pattern - Abnormal spectra =
DISEASE PATTERN
4.
5. Variables
• Height
• width
size & Frequency of each peak
• Combining horizontal and vertical information
• Presence / absence of peak
• Ratio of metabolites
6. METABOLITES
•
•
•
•
•
Cho
- Cell membrane turn over
Cr
- Energy marker -Reference
NAA
- Neuronal cell marker
mI
- Osmolyte
Lactate
- Anerobic state - NOT SEEN
IN NORMAL BRAIN
10. NAA Regional Variations
• NAA peak – Highest due to N acetyl group
• Marker of neuronal / axonal viability and
density
• Evenly distributed in Cerebral hemisphere
• Less in hippocampus and cerebellum
• NAA - Neuronal marker
• Decreases with loss of neuronal integrity.
11. Creatine
•
•
•
•
•
•
•
Energy stores.
Cr 1 - 3.0 ppm
Cr 2 - 3.9 ppm
Marker of intact brain Energy Metabolism.
Reference for interpretation of ratio.
Higher in grey matter than white matter
Higher in thalamus and cerebellum
12. Choline
•
•
•
•
•
Cho
- 3.2 ppm
Present in Cell membrane
Cell membrane turnover
Choline released during disease from pool
Choline - Increased with increased cellular
turnover
• Elevated in tumors and inflammation
13. Choline Regional Variations
• Slightly higher in white matter than gray
• Higher in thalamus and cerebellum
• More choline in pons and terminal zones
of myelination
16. Lipids
•
•
•
•
•
Lip 1 - 0.9 ppm;
Lip 2 - 1.3 - 1.4 ppm
Broad based
Sign of brain injury
Normally Bound - Not seen
Seen when there is cell death and cell membrane
destruction
• Indicates necrosis and / or disruption of myelin
• Difficult to differentiate from macromolecules
• Non significant lipid – from scalp contamination
18. • Glutamine is astrocyte marker
• Glutamate – Neurotransmiter - neurotoxin in
excess amount.
• Main ammonia intake route
• Elevated - In hypoxia, ischemia, recovering
brain.
• Its not a grave prognostic finding like lactate
20. MRS acquisition modes
• STEAM -Stimulated echo acquisition mode
• Single voxel
• Short TE
• PRESS -Point resolved spectroscopy
• Twice the SNR of STEAM
• Short and long TE - single voxel possible
21. PROBE - Single voxel proton MRS
•
•
•
•
•
•
Fully automated prescan, scan
shimming
water suppression
2 -6 minutes Complete acquisition
Short TE (PRESS, STEAM) and
long TE (PRESS)
27. Lactate Vs Lipid
• Lactate is doublet
• Inversion below the
baseline at 144 ms
• Persists at TE 270 ms.
• Lipid peak is broad
• Has a shoulder to left
• Suppressed at TE 270
ms
30. Tumor Biochemistry
• Understood by identifying important
metabolites and quantifying them.
• Comparing with normal and benign
tissues, we can understand metabolite
markers and grade them.
31. Alteration of metabolites in Brain Tumors
• Decreased or absence of N – Acetyl Aspartate (NAA) (Nonneuronal and NAA is only found in neurons)
• Decreased Creatine
• Increased Choline
• Appearance of Lactate (Anaerobic glycolysis)
• Myo-Inositol may distinguish hemangiopericytomas from
meningiomas
• Glutamine and Glutamate are prominent in meningiomas
32. FAQ
• Is it a tumour
• GBM/ Metz/ Abscess?
• Grade?
• Survival?
• ? Oligodentroglioma?
33. Tumour?
• D/D -Stroke, Focal cortical dysplasia,
Herpes and Neoplasm
• ^ Cho – Neoplasm
• Always exclude Demylination - ^ Cho
34. GBM/Metz/Abscess
• Multivoxel PRESS sequence with intermediate
TE -for elevation of Cho in enhancing rim and
in peri-lesional T2 hyperintensity
• If Cho is elevated in both areas - GBM
• Elevated in rim; N –Around - Metz
• Detection of peptides and amino acids in Short
TE - Pyogenic abscess
35. Grade
• Cho/NAA ratio - Most sensitive
index for tumor cell density and
proliferation.
• Marker of tumor infiltration
• High Cho/NAA and Cho/Cr - Fast
growing and high grade neoplasm
36.
37.
38. Prognosis
• High Creatine levels in grade II
gliomas- malignant transformation
and poor survival
• High Cho -Pediatric brain tumors
39. Oligo dentro glioma
Sky-rocketing Choline - high cellular density
MR perfusion:Increased- rCBV- high capillary density
low level of angiogenesis
48. Key points
• High Cho - High tumor cell density & high vascular
proliferation.
• Low Cho and elevation of lipids - Necrosis.
• Cho higher enhancing rim -may be the faster growing
side of the tumor.
• Vasogenic edema -Normal Cho and slightly decreased
NAA.
49. 41y focal seizure
Spectra of active demyelination indistinguishable from
gliomas.
MR perfusion may be helpful.
Tumefactive multiple sclerosis
50. 43 y Focal deficit
• Alanine (Ala) doublet at 1.4 ppm
• Elevation of Cho
• Presence of Lac at 1.3 ppm.
• Absent NAA - Non-neural origin.
• Ala -30–40% of Meningioma
• Mobile lipid and high Cho aggressive lesions
53. • 51y M, GBM Rx RT.
• Reduced Cho, NAA and
Cr relative to normal brain
indicates necrosis.
54. Stroke
• Localized decreased NAA - few hours of ischemia.
• Very low or absent – chronic infarcts.
• Lac is elevated in acute stroke due to anaerobic glycolysis in
ischemic brain.
• Creatine and Choline may change in acute and chronic stroke.
• Lipid - Reflect necrosis.
• MRS is added value to diffusion and perfusion
55. Occlusion of the left ICA /MCA @ 24 h
Left - Elevated Lac and near absent NAA
57. With in 24 hr
Follow-up @ 1 wk
Follow-up @ 5 m
Lac- Elevated
NAA- Preserved
absence of NAA
Lac in infarct region.
High Cho in peri
infarct WM
Reduced NAA
high Cho in WM
No Lac
Lipid + in infarcted
right basal ganglia.
61. Tuberculous vs Pyogenic abscesses
• Similar on MRI.
• Tuberculous abscesses - only Lac and lipid signals @
0.9 and 1.3 ppm; No amino acids
• Lipid peaks –In Both tuberculoma and pyogenic
abscess.
• Amino acid signals helps to discriminate pyogenic
from tuberculous abscess
• @ 135 TE Inv of AA- 0.9 ppm
64. Fungal abscess
• TE 135 proton MR spectrum
from core of abscess - inverted
AA and Lac peaks.
• Multiple signal (*) @ 3.6–3.8
ppm- trehalose
65. Hydatid cyst:
MRS with TE 35 - Lac at 1.33 ppm,
acetate at 1.92 ppm, and succinate at 2.4
ppm;
@TE 135 - Lac and Ala at 1.5 ppm show
phase reversal while Ace and Suc show
normal phase.
66. Neurocysticercosis
• Spectroscopy may be of value in the large
cysticercus cyst without visible scolex, where
differential diagnosis includes brain abscess
and cystic metastases.
• In vivo MRS shows acetate, succinate and Lac.
• Presence of Cr depending on whether the
lesion is in the vesicular or colloid stage
67. HIV encephalopathy
• Reductions in NAA and increases in Cho, mI
in both lesional and normal appearing brain
tissues.
• Toxoplasmosis Vs lymphoma
– Toxoplasmosis -Very large lipid signals
– Lymphoma -Large lipid (smaller than toxo)
-High Cho (not seen in toxo).
69. Demyelination
Multiple sclerosis -
Axonal damage - Decreased NAA
Demyelination - Increased mI, Cho.
Acute MS plaques Decreased NAA and Cr in large plaques
Increased mI, Cho and Lac
Chronic plaque Cr and Lac return quickly to normal,
Cho
- months to return to normal
NAA -may or may not recover to normal.
Tumefactive demyelination may be similar to neoplasm (elevated Cho, Lac,
decreased NAA) –Perfusion useful.
Monophasic Acute Disseminated Encephalo Myelitis - Mild, reversible NAA
reductions without changes in other metabolites - Good prognosis.
70. Multiple sclerosis
• Long TE spectra in acute and chronic MS
lesions.
– Both - Elevated Cho and reduced NAA
– Only acute lesion - Elevated lactate
• Short TE spectra from acute lesion and normal
brain for comparison
– Increased mI, choline, and lipids, slightly
decreased Cr and NAA.
71.
72. Acute Vs Chronic Plaque
• During acute phase- focal increases in Cho and Lac
and decreases in NAA, Cr.
• 15 m later - Reduction of lesion and normalization of
Cho, Cr, and Lactate. NAA- partial recovery.
73. Seizure disorders
• Help in localize and characterize epileptogenic
foci.
• Helps in lateralizing in temporal lobe epilepsy
• @35TE: Decreased NAA, Increased Cho and
mI - Gliosis
• MRS may help to characterize epileptogenic
lesions visible on MRI (aggressive vs. indolent
neoplasia, dysplasia)
74. Ipsilat MRS:
Reduced NAA signal and increased Cho
and mI signals- Gliosis
TLE
Helpful in identification of seizure focus in
refractory pts with normal MR
Contralateral MRS:
Reversible with time - transient neuronal
dysfunction.
Bilateral metabolic changes, associated with
poor post-op seizure outcome
75. Aging and dementia
• Aging - Cho and Cr increase and NAA stable
• AD – Reduced NAA and High mI
• NAA/Cr and mI/Cr ratios correlate with
cognitive function in AD, and this correlation
is more significant with NAA/mI ratios.
• WM NAA/Cr is lower in VaD –than AD
76. AD
• Progression of AD - Regional
elevation of mI/Cr levels in
prodromal AD
• mI/Cr and NAA/Cr - useful for
predicting and monitoring
prodromal AD.
77. Neurodegenerative diseases
• Neuronal dysfunction & cell death.
• Metabolite changes in idiopathic Parkinson’s
disease are inconsistent.
• Multiple system atrophy -reduction in NAA
and NAA/Cr ratio when compared with IPD.
• Lactate increased in Huntington’s disease.
78. Traumatic brain injury
• Conventional CT and MR – major role
• High lactate levels - Poor outcome.
• Visible Lac in normal appearing brain
soon after injury - Poor outcome
• Fall in NAA - Continue for months after
the initial insult.
80. Hypoxic brain injury
• Loss of NAA, increase in Lac and
glutamine and decrease in Cr
• High Lac; low NAA and Cr -Bad
prognosis.
81. In severe HIE distinction
between poor prognosis
and good prognosis is
made on basis of:
(1) excess Lac
(2) decreased NAA
(3) loss of Cr
82. Pediatric white matter disease
• Reduced axonal integrity - Reduced
NAA
• Demyelination -High cho and mI
• Hypomyelination or Gliosis -low
Cho, normal NAA
84. Adrenoleukodystrophy
• Most common leukodystrophy in children
• Zones- demylination, inflamm, gliosis
• MRI often precede clinical symptoms showing
symmetrical WM lesions in parietal and
occipital regions.
• MRS - Onset of demyelination and extent of
WM damage, information for Hemo Stem Cell
Transplant.
85.
86. Inborn errors of metabolism
• Canavan and Salla disease show an elevated NAA
• Maple syrup urine disease -Branched-chain amino
acids at 0.9 ppm.
• Phenylketonuria -Small phenylalanine signal at
7.36ppm (i.e. downfield of water)
• Non-ketotic hyperglycinemia -Glycine at 3.55 ppm
(use long TE to distinguish from mI)
87. Canavan’s disease- AR
• Deficiency of aspartoacylase an enzyme that
deacetylates NAA, Increased free acetate
• Hypotonia and macrocephaly
• Symmetrical confluent subcortical WM T2
prolongation & Centripetal spread
• Bilateral involvement of globi pallidi, thalami,
cerebellum and brainstem
88. NAA is elevated in posterior
sub cortical WM (1) that is
hyper intense on T2 image;
NAA is near normal levels in
(2) is relatively spared by
signal abnormality
89. Maple syrup urine disease
• Deficiency of branched-chain -keto acid dehydrogenase,
catalyzing essential branched-chain amino acids (BCAA)
isoleucine, leucine and valine.
• Hypertonia and hypotonia, irregular respiration and apnea
• Diffusion restriction compatible with cytotoxic edema in pons,
midbrain, pallidi, thalami, cerebellar, and periventricular WM
• Abnormal peak at 0.9 ppm due to accumulation of lactate
(Lac) and loss of NAA
• Prognostic value & monitor response to Rx / diet
• TE 136 ms- avoids lipids
90. Elevation of Lac (1.3 ppm) and of the methyl group of BCAA/BCKA (0.9
ppm).
After therapy at day 12 the two abnormal peaks have disappeared.
91. Phenylketonuria
• Phe hydroxylase def
• Periatrial and periventricular WM symmetrical
hyperintensities.
• Calcifications bilaterally in the globi pallidi
and frontal subcortical regions
• Elevated Phe signal at 7.36 ppm
93. Non-ketotic hyperglycinemia
• Highly elevated glycine in the CSF and
absence of ketoacidosis
• Large glycine peak at 3.55 ppm
• Long TE is necessary to distinguish glycine
resonance from that of mI at 3.56 ppm which
is normally high in neonates
94. abnormal elevation of Gly at 3.55 ppm with a Gly/Cr ~ 1.
Progressive decrease of Gly during treatment with a protein restriction diet
95. Mitochondrial encephalopathy
• Diffuse symmetrical hyperintensity and
volume loss in WM
• mild Lac accumulation in WM, with moderate
NAA and mild Cho and Cr signal losses