MRS
Picture: Magnetic Resonance Spectroscopy.
- Brain tumors: To help differentiate between different types of tumors (e.g., high-grade vs. low-grade), tumors from non-neoplastic lesions like infection or inflammation, or to assess treatment response by distinguishing between tumor recurrence and radiation necrosis.
- Intracranial abscesses: Helps differentiate them from other space-occupying lesions like tumors.
- Stroke: To assess the metabolic changes in areas of stroke.
- Multiple sclerosis (MS): To study the metabolic changes associated with the disease.
- HIV-related encephalopathy: To help in diagnosis, differential diagnosis, and follow-up of the patient's response to therapy.
- Metabolic diseases: To identify metabolic abnormalities.
- Traumatic brain injury (TBI): To evaluate acute changes in brain metabolites after injury, especially in mild TBI.
- Neonatal encephalopathy: To provide additional information about the nature and prognosis of brain injury.
- Liver diseases: To help differentiate liver tissue from neoplastic lesions.
- Prostate cancer: Investigated for its potential role in diagnosis and staging.
- মস্তিষ্কের টিউমার: বিভিন্ন ধরণের টিউমারের (যেমন, উচ্চ-গ্রেড বনাম নিম্ন-গ্রেড), সংক্রমণ বা প্রদাহের মতো নন-নিওপ্লাস্টিক ক্ষত থেকে টিউমারের মধ্যে পার্থক্য করতে সাহায্য করার জন্য, অথবা টিউমার পুনরাবৃত্তি এবং বিকিরণ নেক্রোসিসের মধ্যে পার্থক্য করে চিকিৎসার প্রতিক্রিয়া মূল্যায়ন করার জন্য।
- ইন্ট্রাক্রানিয়াল ফোড়া: টিউমারের মতো অন্যান্য স্থান দখলকারী ক্ষত থেকে তাদের আলাদা করতে সাহায্য করে।
- স্ট্রোক: স্ট্রোকের ক্ষেত্রগুলিতে বিপাকীয় পরিবর্তনগুলি মূল্যায়ন করা।
- মাল্টিপল স্ক্লেরোসিস (এমএস): রোগের সাথে সম্পর্কিত বিপাকীয় পরিবর্তনগুলি অধ্যয়ন করা।
- এইচআইভি-সম্পর্কিত এনসেফালোপ্যাথি: রোগ নির্ণয়, ডিফারেনশিয়াল ডায়াগনসিস এবং থেরাপির প্রতি রোগীর প্রতিক্রিয়ার ফলো-আপে সহায়তা করার জন্য।
- বিপাকীয় রোগ: বিপাকীয় অস্বাভাবিকতা সনাক্তকরণের জন্য।
- আঘাতজনিত মস্তিষ্কের আঘাত (টিবিআই): আঘাতের পরে মস্তিষ্কের বিপাকের তীব্র পরিবর্তন মূল্যায়ন করা, বিশেষ করে হালকা টিবিআইতে।
- নবজাতক এনসেফালোপ্যাথি: মস্তিষ্কের আঘাতের প্রকৃতি এবং পূর্বাভাস সম্পর্কে অতিরিক্ত তথ্য প্রদান করা।
- লিভারের রোগ: লিভারের টিস্যুকে নিওপ্লাস্টিক ক্ষত থেকে আলাদা করতে সাহায্য করার জন্য।
- প্রোস্টেট ক্যান্সার: রোগ নির্ণয় এবং পর্যায়ক্রমে এর সম্ভাব্য ভূমিকার জন্য তদন্ত করা হয়েছে।
- MRS is performed on the same machine as an MRI, but it analyzes the chemical signals (metabolites) in a specific area of the brain.
- It compares the chemical composition of a suspicious area, like a tumor, with that of normal brain tissue.
- The test is sometimes described as a "virtual biopsy" because it can provide detailed information about tissue without needing a surgical procedure.
- MRS can help differentiate between types of brain tumors and determine their grade or aggressiveness.
- It can be used to assess the effectiveness of treatments for brain conditions.
- It is also used to evaluate changes associated with strokes, seizure disorders, and neurodegenerative diseases like Alzheimer's.
- You will lie still in an MRI scanner, similar to a standard MRI.
- You will be asked to avoid caffeine beforehand and remove all metal jewelry.
- You may be given an injection of contrast dye to enhance the images.
PREPARATION
- MRI, CT Scan Report with Films.
- Blood for Serum Creatinine for Contrast.
- Histopathology Report.
- Operation Note.
PROTOCOL (Philips)
- Survey
- T2W_TSE-----------------SAG
- T2W_TSE-----------------COR
- T2W_TSE-----------------TRA
- MV_PRESS_144---------MV
- MV_PRESS_288---------MV
BRAIN SPECTRA
What do the peaks seen in routine brain MRS represent?
Picture: Normal brain ¹H spectrum at short TE
Picture: Normal brain ¹H spectrum at short TE (35 ms) shows
characteristic peaks described below
Three major ¹H spectral peaks are consistently
identified in the normal brain at 1.5T and 3.0T: NAA (N-acetyl
aspartate), Cr (creatine), and Cho (choline). When relatively short
echo times are used, peaks for mI (myo-inositol) and Glx
(glutamate/ glutamine) may be seen. Lac (lactate) is not present
in the normal adult brain but may be identified in neonates. Broad peaks due to
mobile lipids (Lip) and macromolecules (MM) are also a well
recognized feature of spectra obtained at short TE values. At
very high fields (≥7.0T) and in certain diseases small additional peaks may be
identified, described in the Advanced Discussion.
A brief summary of the commonly seen major brain metabolites
and their principal spectral peaks is provided below. Although each metabolite
has several chemically distinct ¹H nuclei contributing to the spectrum,
usually only one (or two) of these are large enough to be detected in clinical
MR studies.
1. N-acetyl aspartate (NAA)
- Tallest peak in spectrum (δ = 2.0)
- Present primarily in neurons – a marker of neuronal density and viability
- Decreased in any disease that destroys neurons (stroke, MS, tumor, dementia, epilepsy)
- Metastatic and non-neural neoplasms (meningiomas) do not contain NAA
- Elevated in Canavan's disease
Picture: N-acetyl aspartate (NAA)
2. Creatine (Cr)
- Two peaks (at δ = 3.0 and 3.9, corresponding to blue and red hydrogens, respectively)
- Peak includes both Creatine (Cr) and Phosphocreatine (PCr), involved in energy metabolism
- PCr + ADP ↔ ATP + Cr
- Produced in liver and transported to brain where its level is relatively constant; serves as internal standard
- Decreased in most brain diseases; absent in metastases
Picture: Creatine (Cr)
3. Choline (Cho)
- 3rd tallest peak (δ = 3.2)
- Includes dominant contributions from phosphorylcholine and glycerophosphorylcholine; free Cho content is low in normal brain
- Major constituents of cell membranes
- Elevated in diseases with high membrane turnover (ischemia, demyelination, tumors, inflammation)
- Especially elevated in malignancy, where Cho/Cr ratio may be inverted
Picture: Choline (Cho)
4. Myo-inositol (mI)
- Several multiplet peaks, largest near δ = 3.6; isomer scyllo-inositol (sI) is small singlet at 3.3 ppm
- Glucose-like metabolite found principally in astrocytes; regulates cellular volume
- Due to short T2, best seen on short TE studies
- Elevated in neonates, gliosis, acute demyelination, schwannomas, tuberous sclerosis, cortical dysplasias
- Decreased in any chronic process destroying astrocytes (ischemia, neoplasm, demyelination)
Picture: Myo-inositol (mI)
5. Glutamate/Glutamine (Glx)
- Glutamate (Glu) is shown. For Glutamine (Gln) the left O− is replaced by NH2 Glutamate (Glu) is the major excitatory neurotransmitter released by neurons
- Nearby astrocytes take up glutamate, converting it to glutamine (Gln) which is recycled to the neuron for reprocessing into glutamate
- Glutamate and glutamine resonate closely together, their summed peak called Glx and assigned to δ ≈ 2.3
- Increased in hepatic encephalopathy and many acute brain diseases (stroke, demyelination, epilepsy)
6. Lactate (Lac)
- Peak at δ = 1.3, characteristic doublet that is upright at TE = 30 and 288 ms, but inverted at TE = 144 ms
- Not present in normal brain (except neonates)
- Product of anaerobic metabolism
- Elevated in ischemia/infarction (hypoxia), in tumors (glycolysis and increased oxygen demand), and spectral "contamination" by CSF (which normally contains Lac)
Picture: Lactate (Lac)
7. Lipids (Lip)
- Signals arise from mobile tissue triglycerides and free fatty acids
- Two broad peaks at δ = 0.9 ppm (−CH3) and 1.3 ppm (−CH2−), best seen on short TE spectra
- Increased in wide range of destructive cellular processes (necrosis, inflammation, malignancy)
- Macrophages often contain high Lip concentrations
8. Macromolecules (MM)
- At least 40 short but wide overlapping peaks, the largest in bands between δ = 0.9−2.2 and 3.7−4.2 ppm
- Due to very short T2 values seen only at short TE's and contribute undulation in spectral baseline
- Responsible metabolites not fully identified, but thought to arise from amino acid residues in >3500 Da proteins and polypeptides of brain cytosol
- MM peak elevated in any disease that injures brain cells
Less Commonly Observed Brain Specta
Alanine (Ala) is a small amino acid whose major
spectral peak is a doublet from its methyl group at 1.46 ppm. This doublet
overlaps with the lactate doublet, and like lactate, inverts at
intermediate TE values (~144 ms). Ala also has a second smaller peak
at 3.77 ppm. Ala levels may be elevated in meningiomas, central neurocytomas,
and primitive neuroectodermal (PNET) tumors. Elevations are also reported in
demyelination and bacterial abscesses.
Acetate (Ac), the anion of acetic acid, commonly
accumulates in bacterial abscesses due to enhanced glycolysis and fermentation
by the infecting organism. It produces a singlet peak at 1.91 ppm. Acetate is
also elevated in the in Canavan's disease due to deficiency of the enzyme
aspartoacyclase.
Branched Chain Amino Acids (leucine, isoleucine, valine) may
be identified in patients with various inborn errors of metabolism such as
maple syrup urine disease. They are also seen in pyogenic and fungal (but not
tuberculous) abscesses. Their principal multiplet peaks lie in the 0.9 – 1.0
range and may invert when intermediate TE values (~144 ms) are used.
Ethanol, the primary ingredient in alcoholic beverages,
may be detected in intoxicated patients, characterized by its main triplet peak
at 1.19 ppm.
GABA (γ-aminobutyric acid) is the principal
inhibitory neurotransmitter in the central nervous system. It has three
relatively equal-sized peaks at 1.90, 2.30, and 3.02 ppm. Due to its low
concentration compared to other more prominent overlapping (NAA and Cho) peaks,
special MRS methods such as spectral editing are needed to identify and resolve
GABA resonances.
Galactose, a monosaccharide sugar, and its
metabolites galactitol and galactonate, have resonances around
3.7 that may be detected in patients with the inborn error of metabolism, galactosemia.
Glucose, the principal monosaccharide circulating as
blood sugar, may be detected during extreme hyperglycemic states such as
diabetic ketoacidosis. Principal resonances are at 3.43 and 3.8 ppm.
Glycine (Gly), the smallest the amino acids, has a
primary resonance at 3.56 ppm. It is elevated in many brain tumors
(glioblastomas, ependymomas, medulloblastomas) and is especially prominent in
central neurocytomas. It may also be seen in the spectra of the brain and other
organs in nonketotic hyperglycinemia (an inborn error of Gly metabolism).
2-Hydroxyglutarate (2-HG) accumulates in gliomas
that have mutations in isocitrate dehydrogenase. Has a small doublet at 2.3 ppm
that may be separated from background macromolecules, Glx, and GABA resonances
by spectral editing.
Ketone bodies, including acetone (2.22
ppm), acetoacetate (2.26 and 3.46 ppm) and β-hydroxybutyrate (doublet
peaks at 1.15 and 1.25 ppm) can be detected in patients on ketogenic diets and
in those with diabetic ketoacidosis.
Mannitol, an exogenously administered sugar alcohol used
for treatment of increased intracranial pressure and low output renal failure,
produces a detectable peak at 3.8 ppm.
Phenylalanine, an aromatic amino acid, has its prominent
resonances in the downfield part of the spectrum (i.e., to the left of water)
in the 7.31-7.43 range, seen in the inborn error of metabolism,
phenylketonuria.
Succinate, the anion of succinic acid, is a component of
the citric acid cycle. Its singlet peak at 2.4 ppm is often seen together with
that of acetate (1.9) and is a marker for anaerobic pyogenic infections as well
as cysticercosis. Also elevated in rare enzyme defect succinate dehydrogenase
deficiency.
Taurine, a ubiquitous amino-sulfonic acid, is inhibits
neural transmission and stabilizes cell membranes. It has two peaks (one at
3.25 ppm, usually obscured by Cho) and a second at 3.42 ppm, just on the left
shoulder of Cho. It is elevated in a wide range of disorders, but especially in
primitive neuroectodermal tumors (PNET/medulloblastoma/retinoblastoma) and
metastatic renal cell cancer.
Trehalose is a disaccharide synthesized by
unicellular organisms, especially cryptococcus, seen in fungal abscesses.
Spectrum has more than a dozen closely spaced peaks between 3.4 and 3.9 ppm
Peaks
It is the Time of Echo (TE) that conditions the number of
measurable metabolites: long TE (136-272 ms) vs short TE (10-50 ms) 7-8.
- lactate: resonates at 1.33 ppm
- lipids: resonates at 1.3 ppm
- alanine: resonates at 1.48 ppm
- N-acetylaspartate (NAA): resonates at 2.0 ppm
- glutamine/glutamate: resonates at 2.2-2.4 ppm
- GABA: resonates at 2.2-2.4 ppm
- 2-hydroxyglutarate: resonates at 2.25 ppm 6
- citrate: resonates 2.6 ppm
- creatine: resonates at 3.0 ppm
- choline: resonates at 3.2 ppm
- myo-inositol: resonates at 3.5 ppm
- water resonates at 4.7 ppm
Less common peaks
- propylene glycol: resonates at 1.14 ppm
- ethanol: resonates at 1.16 ppm
- acetate: resonates at 1.9 ppm
- acetone: resonates at 2.22 ppm
- acetoacetate: resonates at 2.29 ppm
- succinate: resonates at 2.4 ppm
- methylsulfonylmethane: resonates at 3.15 ppm
- scyllo-inositol: resonates at 3.36 ppm
- taurine: resonates at 3.4 ppm
- glucose: resonates at 3.43 ppm and 3.8 ppm
- mannitol: resonates at 3.78 ppm
- lactate quartet: resonates at 4.11 ppm
NB: ppm = parts per million
Related pathology
Glioma
MRS can help increase our ability to predict grade.
As the grade increases, NAA and creatine decrease and choline, lipids and
lactate increase.
In the setting of gliomas, choline will be elevated
beyond the margins of contrast enhancement in keeping with cellular
infiltration.
Non-glial tumours
May be difficult but in general non-glial tumours will
have little, if any, NAA peak.
Radiation effects
Distinguishing radiation change and tumour recurrence can
be problematic. In recurrent tumour choline will be elevated, whereas in
radiation change, NAA, choline and creatine will all be low.
Ischaemia and infarction
Lactate will increase as the brain switches to anaerobic
metabolism. When infarction takes place then lipids are released and peaks
appear.
Infection
As in all processes which destroy normal brain tissue,
NAA is absent. Within bacterial abscess cavities, lactate, alanine, cytosolic
acid and acetate are elevated/present.
Of note choline is low or absent in toxoplasmosis,
whereas it is elevated in lymphoma,
helping to distinguish the two.
White matter diseases
progressive
multifocal leukoencephalopathy (PML) may demonstrate elevated
myoinositol
Canavan
disease characteristically demonstrates elevated NAA
Hepatic encephalopathy
Markedly reduced myoinositol, and to a lesser degree
choline. Glutamine is increased.
Mitochondrial disorders
Leigh
syndrome: elevated choline, reduced NAA and occasionally elevated lactate
Mnemonic
- My ChoCrNaaLa (think of a new chocolate energy bar or something)
- My: Myo-inositol 3.5
- Cho: Choline 3.2
- Cr: Creatine 3.0
- Naa: Naa 2.0
- L: Lactate 1.3
History and etymology
MRS of intact biological tissues was first reported by two groups: Moon and Richards using P-31 MRS to examine intact red blood cells in 1973, and Hoult et al. using P-31 MRS to examine excised leg muscle from the rat in 1974. The first MR spectrum of a human brain in vivo was published in 1985 by Bottomley.
