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MRS Basics, Clinical Applications & Case Studies
1. MR SPECTROSCOPY (MRS) :
Basics & Clinical applications
Dr. Rahi Kiran.B
Senior Resident, Neurology
Govt Medical College, Kota
2. • Also known as Nuclear Magnetic Resonance (NMR).
• Based on the nuclei's quantum mechanical properties.
• Keep foremost in mind –
– Information provided by MRS is complementary to the
other imaging data
– Properly interpreted only when all of the imaging
(including functional) information is incorporated
• Superior for clinical studies when necessary to obtain
metabolic information of a large or heterogenous lesion.
• In addition, spectral information from control regions can be
obtained simultaneously.
3. WATER AND FAT SUPPRESSION
• It is essential to suppress the water and the lipid peaks which
are in very high concentrations to reliably measure the
metabolite contractions.
4. MAJOR METABOLITES
N – ACETYL ASPARTATE (NAA) :-
• The most prominent spectral peak in the normal brain.
• found almost exclusively in neurons and serves as a marker of
neuronal density and viability.
• Extremely metabolically active, with 100% turnover in
approximately 16 hours.
• role as a messenger molecule between neurons, astrocytes,
oligodendrocytes, and possibly microglia.
5. Total Creatine
• high-energy phosphate reservoir for the generation of ATP.
• Creatine is present in brain, muscle, and blood
• As Cr serves as a marker for energy-dependent systems in
cells, it tends to be low in processes that have low
metabolism, such as in necrosis and infarctions.
• the Cr resonance is often used as an internal standard and
changes in metabolite ratios with creatine as the denominator
are typically interpreted as changes in the metabolite in the
numerator. For example-decline in NAA/Cr is usually
interpreted as a decline in NAA.
6. Choline containing compounds :-
• Changes in this resonance commonly seen with diseases that
have alterations in membrane turnover.
• increased in most processes that are accompanied by
hypercellularity .
• Diseases such as neoplasms and leukodystrophies result in a
substantial increase in MRS-visible Cho .
7. Myoinositol :-
• The function of MI is not fully understood - ? osmolyte, and ?
storage form for glucose.
• MI is primarily located in glia, and an increase in MI is
commonly believed to be a marker of gliosis .
• decreased in high-grade primary brain tumors
• Elevated in Alzheimer disease , AIDS dementia, other
neurodegenerative diseases, and brain injury.
8. Lactate
• normal conditions - very low.
• Indicate anaerobic metabolism.
• It has been reported that lactate levels after acute stroke
correlate strongly with ADC values .
• Increased lactate has been found during hypoxia ,
mitochondrial diseases , and seizures and in the first hours
after birth.
• The presence of lactate in brain tumors- Occurs in highly
cellular and metabolic lesions that outgrow their blood supply
as its presence indirectly measures glucose utilization.
9. Lipids
• may obscure the presence of lactate
• generally found in necrosis - indicators of high-grade
malignancies.
10. Glutamate and Glutamine
• Cerebral Glu concentration is reported to be increased in
cerebral ischemia , hepatic encephalopathy , and Rett
syndrome .
Gamma Amino Butyric acid
• reduced or abnormal GABA in several neuropsychiatric
disorders, including epilepsy, anxiety disorders, major
depression, and drug addiction.
11.
12. • So in MR spectroscopy (MRS) :-
–NAA is considered as a good metabolite (as it
represents neuronal health)
–Choline is considered as a bad metabolite (as it is seen
in tumors) and
–Lipid lactate doublet as an ugly metabolite (as it is
seen in necrotic tumors).
14. CLINICAL APPLICATIONS OF MRS
CLASS A APPLICATIONS : Useful in INDIVIDUAL Patients :-
• ICSOL’s – particularly Intra-axial
• Differentiating Brain Neoplasm from Non-neoplastic
• Primary CNS Neoplasm vs Metastasis
• Radiation Necrosis vs Recurrent Tumors
• Inborn errors of Metabolism
15. CLINICAL APPLICATIONS OF MRS
CLASS B APPLICATIONS :
OCCASIONALLY useful in INDIVIDUAL Patients :-
• Ischemia, Hypoxia and Related Brain Injuries
– Acute Ischemic stroke
– Cardiac arrest and global hypoxia
– Near drowning
– Hypoxia- Ischemia in Neonates
• Epilepsy
16. CLINICAL APPLICATIONS OF MRS
CLASS C APPLICATIONS :
Useful Primarily in GROUP Of Patients (RESEARCH) :-
• NeuroAIDS
• Opportunistic Infections
• Neurodegenerative diseases –
– Alzeimer disease
– Parkinson disease and plus syndromes, ALS, MS, HD
• Hepatic encephalopathy
• Traumatic Brain injury
• Psychiatric disorders
17. Charecterstic peak & varoius ratio in MRS
Disease Peak Ratio
Tuberculosis Prominent large lipid peak Prominent decrease in
NAA/Cr, Cho/Cr>1
Neurocysticercosis Cytosoloic amino acid peak Prominent decrease in NAA/cr
Abscess Cytosoloic amino acid peak,
lipid lactate peak
Prominent decrease in NAA/cr
Modest decrease in
Choline/Cr
Glioma Raised Cho/Cr, lactate & lipid
in high grade
Very Low NAA/Cr
Lymphoma markedly elevated
Cho/Cr, massively elevated
lipid
Low NAA
Tumefactive MS Raised Cho/Cr, raised
myoinositol
Low NAA in centre(less
prominent than glioma)
PML Raised Cho/Cr, lactate & lipid decrease in NAA/cr
18. ICSOL’S
• The typical 1H MR spectrum of a neoplasm :-
– Substantial elevation of Cho
– a reduction of NAA and
– little or minor changes in Cr.
• So a high Cho/NAA ratio (>2:1)- strong indicator of a higher-
grade neoplasm.
• But a low Cho/NAA ratio could arise from :-
– low-grade neoplasm
– low neoplastic cellular density or
– Non-neoplastic processes such as multiple sclerosis.
19. A Cho/NAA ratio > 1.3 -
reported to have a high
accuracy for detection of
neoplasm.
Cho/Cr ratio - less reliable
Nonenhancing high-grade
lesions-increased Cho and
Cho-Cr ratios
Contrast-enhancing
lesions-lymphoma,
glioblastoma, or metastasis
20. PRIMARY CNS NEOPLASM VS METASTASIS
• most primary brain neoplasms – infiltrative whereas metastatic
deposits -more localized.
• The gradient of decline in Cho - more abrupt with metastasis, more
gradual - gliomas
RADIATION NECROSIS VS RECURRENT TUMOR
• True necrosis - an absence of the typical brain metabolite signals
and an increase in lipid signals.
• Radiation induced changes - elevated Cho, although not to the
extent that is seen in high-grade neoplasms.
21. INBORN ERRORS OF METABOLISM
• not specific for a certain disorder.
• Alexander-reduced NAA
• Canavan-Increased NAA
• Krabbe-Both NAA and lactate reduced
22. ACUTE ISCHEMIC STROKE
• MRS can be useful in assessing the severity of ischemia within
the region that is being perfused by collateral flow.
• When collateral flow is adequate to maintain normal
metabolism, the MR spectrum even in hypoperfused areas
defined by MR perfusion imaging will appear normal.
• With further reduction of perfusion, progression to frank
ischemia will result in the elevation of lactate and the
reduction of NAA.
23. HYPOXIA-ISCHEMIA IN NEONATES
• can add additional information.
• Typical - decline in NAA and an elevation of lactate.
• In children with neurodevelopmental impairment,
• lactate was still found 1 year after perinatal asphyxia
• Further research still continued.
24. EPILEPSY
• Metabolic changes can be detected by MRS, including the
production of lactate and, if prolonged, the reduction of NAA .
• elevation of lactate, can be observed some time after seizure
activity ceases.
• More common for MRS to be obtained interictally.
• The purpose is to help localize the source of the seizures-mc -
Temporal lobe epilepsy (TLE).
25. NeuroAIDS
• Demonstrated a significant increased Cho-Cr levels and
reduction in levels of NAA in the brains of these patients .
• 1H MRS has been useful in studies on the effects of therapies
and their mechanism of action.
• Reversal of the metabolic abnormalities reported with ART.
26. OPPORTUNISTIC INFECTIONS
• The most common is toxoplasmosis, which presents as
enhancing masses or ring-enhancing lesions in the brain.
• Toxoplasmosis can be difficult to differentiate from primary
CNS lymphoma and pyogenic abscesses using structural
imaging alone.
• MRS - Toxoplasmosis typically has a significantly lower level of
Cho than observed with lymphoma.
27. NEURODEGENERATIVE DISEASES
• With progression to more severe neurodegeneration, a
substantial decline of NAA accompanied by an elevation of
Cho and possibly MI.
• mostly used in research studies.
• MRS may become much more important clinically in the
future when drugs are developed to treat these diseases-
reversal of NAA levels.
30. Lobulated, intensely
enhancing mass within the
third ventricle. A biopsy
resulted in a diagnosis of a
choroid plexus papilloma.
Single-voxel spectroscopy
from the mass reveals a very
high level of choline.
Choroid plexus papilloma
31. A 14 Y M WITH REFRACTORY CPS PLANNED FOR SURGERY
•Conventional MRI
revealed no apparent
abnormality.
•MRS of Left anterior
hippocampus showed
smaller NAA peak (33%
less) compared to Right
Left
Left Temporal lobe epilepsy
NAA
32. A 50 yr M with fever, headache and Lt hemiparesis
B, Axial T2-weighted image showing ring
lesion with surrounding hyperintensity
and mass effect., ring-shaped cystic
lesion and surrounding edema, With
diffusion restriction
DDx- ?abscess, ?tumor
MRS from the lesion show peaks lactate and
amino acids.
Lactate
Amino acids
Pyogenic abscess
33. A 48 Y F WITH HEADACHE AND LEFT HEMIPARESIS
Coronal contrast-enhanced T1-weighted MR
image shows a large right temporal mass with
rich contrast uptake with extensive midline
shift.
Meningioma
Spectrum of the lesion shows increased
Cho/Cr ratio and an absence of NAA as it is a
extraaxial mass.
34. A 27 Y M WITH MULTIPLE NODULAR LESIONS IN BRAIN
multiple small nodular areas of
enhancement redominantly
located at gray white
junction.
DDx- ?Multiple tuberculoma,
?Multiple NCC
MRS lipid peak, NAA and Cr are
barely detectable
Multiple tuberculoma
lipid
35. FUC OF A 48YR F WITH PROVEN GLIOBLASTOMA MULTIFORME
TREATED WITH SURGERY, EXTERNAL BEAM RADIATION AND
INTERSTITIAL BRACHYTHERAPY.
enhancement of a left frontal
lobe/insular lesion that has both solid
and cavitary components
DDx- ?Recurrent tumor,
?Radiation necrosis
MR spectrum shows a
prominent lipid/lactate peak
with minimal residual Cho
and Cr; NAA is absent.
Lip
Lac
Cho Cr NAA
Radiation necrosis
36. A 6 months old child with developmental delay.
Canavans disease
37. 5 YRS CHILD WITH SEIZURES & 2 STROKE LIKE EPISODES
A – T 2 W- hyperintenseleft
occipital region.
B- MRS –inverted doublet lactate
peak, significant Cho and NAA
reduction
MELAS
lactate
40. toxoplasma abscess
"Eccentric target sign“, less prominent
choline peak and reduced NAA, large
lipid lactate peak
51-year-old male,
known HIV sero-
positive, initially
asymptomatic, came
with complaints of
generalized weakness
since 2 months
toxoplasma abscess vs
lymphoma.
41.
42. MRS
Dec NAA/Cr
Inc acetate,
succinate,
amino acid,
lactate
Neuodegener
ative
Alzheimer
Dec
NAA/Cr
Dec NAA/
Cho
Inc
Myo/NAA
Slightly inc Cho/ Cr
Cho/NAA
RaisedMyo/NAA
± lipid/lactate
Inc Cho/Cr
Myo/NAA
Cho/NAA
Dec NAA/Cr
± lipid/lactate
Malignancy
Demyelinating
disease Pyogenic
abscess
Lipid increase in high-grade gliomas, meningiomas, demyelination, necrotic foci, and inborn errors of metabolism
NAA is the most prominent one in normal
adult brain proton MRS and is used as a reference for
determination of chemical shift and nonspecific
neuronal marker. Normal absolute concentrations of NAA in the adult
brain are generally in the range of 8 to 9 mmol/kg. NAA concentrations
are decreased in many brain disorders, resulting in neuronal
and axonal loss, such as in neurodegenerative diseases,
stroke, brain tumors, epilepsy, and multiple sclerosis, but
are increased in Canavan's disease
Cr peak is an indirect
indicator of brain intracellular energy stores, tends to be relatively constant in each tissue
type in normal brain, mean
absolute Cr concentration in normal adult brains of 7.49; reduced in all brain tumors, particularly
malignant ones
Cho reflects cell membrane synthesis and
Degradation. Processes resulting in hypercellularity
(e.g., primary brain neoplasms or gliosis) or myelin
breakdown (demyelinating diseases) lead to locally increased
Cho concentration, whereas hypomyelinating diseases
result in decreased Cho levels. Mean absolute Cho concentration in
normal adult brain tissue of 1.32
Ig3 MI is believed to be a glial
marker because it is present primarily in glial cells and is
absent in neurons; abnormally increased in
patients with demyelinating diseases and in those with
Alzheimer's disease
Lac levels in normal brain tissue are absent or extremely low (C0.5
Mmol/L), they are essentially undetectable on normal spectra. Found in anaerobic glycolysis,
which may be seen with brain neoplasms, infarcts, hypoxia,
metabolic disorders or seizure and accumulate
within cysts or foci of necrosis.