2. Outline
• Introduction
• Normal spectra
• Major Metabolites in the Brain
• MRS Acquisition modes
• Clinical applications
• Reference
3. Introduction
• Noninvasive means of assessing the biochemical and metabolic
processes in intracranial tissues
• Provide Complementary information for several disease
• There are numerous metabolites found in the human brain.
• Fortunately, only several of them are useful in spectroscopic studies.
• Should always be correlated with the structural MR images
4. Normal Spectra
• Metabolites is plotted on a two dimensional graph.
• Horizontal axis - frequencies (chemical shifts)
• Reference to a stable compound(tetramethylsilane (TMS)- 0 ppm.
• Expressed as parts per million (ppm)
• Tissue’s chemical environment determines the frequency of a “metabolite
peak”
• Vertical axis represents the concentration of the metabolites.
5.
6. Major Metabolites in the Brain
• NAA
• Choline
• Creatine
• Lactate
• Lipid
• Glutamine
• Myo-Inositol
• Alanine
7. N-ACETYLASPARTATE (NAA)
• Marker of neuronal density and viability.
• NAA is the tallest peak in the spectrum and
assigned at 2.0ppm
• Its concentration appears to decrease with any
brain insults such as infection, ischemic injury,
neoplasm, and demyelination process.
• Not found in tumors outside the CNS such as
meningioma.
• Canavan disease is the only disease in which
NAA is increased.
8. Choline
• Choline is the second largest peak and assigned to
3.2 ppm
• It is the precursor of acetyl choline- neurotransmitter
and
• phosphatidylcholine-integral part of cell membrane
synthesis
• Disease processes affecting the cell membrane
and myelin can lead to the release of
phosphatidylcholine.
– Thus, elevation of choline can be seen during ischemic
injury, neoplasm or acute demyelination diseases.
9. Creatine (Cr)
• Cr is the third highest peak and is assigned to 3.03
ppm
• The overall level of total creatine in normal brain is
fairly constant.
• phospocreatine + ADP = ATP+ creatine
• Reduced Cr level may be seen neoplasm, ischemic
injury, infection or some systemic diseases.
• Most metastatic tumors to the brain do not
produce creatine - do not possess creatine kinase.
10. Lactate
• Lactate levels in the brain are normally are very low or absent.
• When oxygen supply is depleted, the brain switches to anaerobic respiration
for which one end product is lactate.
– Therefore, elevated lactate peak is a sign of hypoxic tissue.
• Low oxygen supply
– decreased oxygen supply (eg vascular insults, or hypoventilation) or
– increased oxygen requirement (eg. neoplastic tissue or epilepsy)
11. • Lactate peak occurs at two different locations.
– Lower field peak (a doublet) occurs at approximately 1.32 ppm.
– The other peak (a quartet) is seen at 4.1 ppm and this is very close
to the water peak.
• usually suppressed during data processing.
12. Lipids
• These substances are incorporated into cell membranes and myelin.
• Lipid peak should not be seen unless there is destructive process of the brain
– including necrosis, inflammation or infection.
• Have very short T1 relaxation time - not seen unless short TEs are utilized.
• Lipid resonance at 1.2 ppm can sometimes obscure the lactate peak at 1.32 ppm.
• Fat in the cranium can contaminate the true disease process if the voxels are placed too close
the cranium.
13. Myo-Inositol (mI)
• It is found mainly in astrocytes
• Helps to regulate cell volume.
• Elevated level of mI would be seen where there is glial cell
proliferation as in gliosis.
• The main mI peak is assigned to 3.56 ppm
14. Glutamate and Glutamine (Glx)
• Glutamate is an excitatory neurotransmitter
• Glutamine and glutamate resonate closely together.
– Their sum is often designated as Glx and is assigned between
2.1 and 2.5 ppm.
20. MRS Acquisition Technique
• Can be performed at either 1.5 or 3.0 T within 10-15 minutes
• Should always be correlated with the MR images
• The most common nuclei that are used are
– 1H (proton), 23Na (sodium), 31P (phosphorus).
• Proton spectroscopy is easier to perform and provides much higher SNR
21. • Because the signal from the water peak is very large when compared with that
of other metabolites, it needs to be suppressed for adequate visualization of other
peaks
– (the concentration of water can be 10 000 times the concentration of other metabolites).
• The most frequently used method for suppressing the signal from water is
chemical shift selective excitation (CHESS), which reduces the water signal by
a factor of 1000.
• Fat is avoided by placing the voxel away from the fat in bone marrow and scalp.
22. • Using long TEs, the signal from most metabolites in the brain is lost except
that of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), and lactate.
• Conversely, short TEs allow for identification of many other metabolites (eg,
myoinositol, glutamate, glutamine, and glycine).
fig :Glx (glutamine) and myoinositol (mI) have short T2 values and are not visible on
long TE spectra.
23. SINGLE VOXEL V/S MULTI VOXEL
• As a general rule, the single voxel, short TE technique is used to make the
initial diagnosis as the SNR is high and all metabolites are represented.
• Multi voxel, Long TE technique is used to further characterize different
regions of the mass and to assess brain parenchyma adjacent to the mass.
• A voxel should include as much of the abnormality as possible and little
(generally less than 20% of the voxel size) normal surrounding brain
24. Multi voxel spectroscopy
•A single slice is defined through the area of interest, and then a box is specified within this (white lines). Spectra
will then be generated for all voxels within the box.
•The lesion spectra demonstrate decreased NAA (a marker of neuronal integrity) and increased choline (a
marker of myelin breakdown). The short TE spectrum demonstrates elevated myo-inositol (a marker of glial
cells)
•This figure presents the spectra for a low grade brainstem glioma.
25. Clinical applications
1) Brain Tumors
•MRS can be used to determine the degree of malignancy.
•As a general rule, as malignancy increases, NAA and creatine decrease, and choline, lactate,
and lipids increase.
• NAA decreases as tumor growth displaces or destroys neurons.
• Very malignant tumors have high metabolic activity and deplete the energy stores, resulting in
reduced creatine.
• Very hypercellular tumors with rapid growth elevate the choline levels.
• Lipids are found in necrotic portions of tumors
• Lactate appears when tumors outgrow their blood supply and start utilizing anaerobic glycolysis.
27. Brain Tumors cont..
• To get an accurate assessment voxel should be placed over an
enhancing region of the tumor, avoiding areas of necrosis,
hemorrhage, calcification, or cysts
• Multi-voxel spectroscopy is best to detect infiltration of malignant cells
beyond the enhancing margins of tumors.
– Particularly in the case of cerebral glioma, elevated choline levels are
frequently detected in edematous regions of the brain outside the enhancing
mass.
• MRS direct the surgeon to the most metabolically active part of the
tumor for biopsy
28. A, Axial postcontrast MR T1-
weighted image shows the position of a
single voxel
B, Proton MR spectroscopy shows
patterns similar to those seen in
astrocytomas with elevated Cho and low
NAA.
No obvious lactate or alanine.
C, Axial precontrast MR T1-
weighted image shows location of
the volume of interest within a
frontobasal meningioma
(surgically proved).
D, Proton MR spectra show Cho (1), Cr
(2), and a peak (A–L) at 1.3 to 1.4 ppm,
corresponding to alanine and/or lactate.
No definite NAA is identified-non-
neuronal origin
30. Metastasis
•Intratumoral choline peak with no choline elevation in the peritumoural edema
•Any tumor necrosis results in a lipid peak
•NAA depleted
FIG:
•A, Single-volume proton MR spectroscopy in a solitary brain metastasis (proved small-cell
carcinoma). Note decreased NAA with respect to Cho and Cr, which appear elevated. Large
peaks (small and large asterisks) are probably combination of lactate and lipids.
•B, Axial MR T2-weighted image shows the position of the voxel with respect to the lesion.
•Note that the voxel is eccentric to the lesion to avoid skull and subcutaneous fat.
31. Recurrent tumor vs Radiation necrosis
• A common clinical problem is distinguishing tumor recurrence from
radiation effects
• Elevated choline is a marker for recurrent tumor.
• Radiation change generally exhibits low NAA, creatine, and choline
• If radiation necrosis is present, the spectrum may reveal elevated
lipids and lactate.
32. • Volume 21 shows low NAA, high Cho, and lactate (arrow) compatible with a recurrent tumor
• Volume 24 shows no NAA, low Cho, and a “death peak” (combination of lactate and
cellular breakdown products).
– Radiation-induced necrosis shows large death peak.
33. 2) Infectious Diseases
1) Brain abscesses
• voxel should include the abscess cavity to detect the breakdown products
• Destroy or displace brain tissue-NAA is not present.
• Lactate,alanine, and acetate are characteristic metabolites in pyogenic abscesses
34. Infectious Diseases con..
2) Toxoplasmosis and tuberculomas
•show prominent peaks from lactate and lipids.
•Choline is low or absent in toxoplasmosis
3) cryptococcoma
•Decreased Lactate
35. MRS in AIDS
AIDS dementia complex
•MRS shows a net reduction of NAA and decreases of NAA/Cho and NAA/Cr
ratios.
•Choline is the best marker for the white matter abnormalities
•The extent of NAA depletion correlates directly with the degree of dementiea
•Choline - Elevated in lymphoma
-Decreased in toxoplasmosis, tuberuloma and cryptococcoma.
36. Toxoplasmosis vs lymphoma
• both - increased lactate and lipids
– although this tends to be less marked in lymphoma
• lymphoma typically demonstrates marked increase in choline, whereas it
is reduced in toxoplasmosis
• both lesions demonstrate decreased creatine and NAA
primary CNS lymphoma
37. 3) Cerebral Ischemia and
Infarction
• When the brain becomes ischemic, it switches to anaerobic
glycolysis and lactate accumulates.
– Markedly elevated lactate is the key spectroscopic feature of
cerebral hypoxia and ischemia.
• Choline is elevated, and NAA and creatine are reduced.
• If cerebral infarction ensues, lipids increase.
38. The MRS demonstrates elevated lactate peak and depressed NAA peak in the area of
infarction, indicating ongoing neuronal necrosis.
39. 4) Epilepsy
• During seizure, the metabolic demands > exceed the supply of oxygen and
nutrients to the portion of the brain undergoing enhanced electrical activity.
• Production of lactate, if prolonged, reduction of NAA .
• Elevation of lactate can still be observed some time after seizure activity ceases.
• Purpose is to localize the source of the seizures.
– Most common clinical scenario - Temporal lobe epilepsy (TLE).
40. Temporal lobe epilepsy
•A 37-year-old male patient with a
longstanding history of medically
intractable and partial complex
seizures.
•Single-voxel MRS shows a
decrease in N-acetylaspartate in
the right temporal lobe compared
to the right .
41. 5) Trauma
• Not routinely used in the acute setting of head injuries.
• Helpful to assess the degree of neuronal injury and predict patient
outcomes.
– Especially in the case of DAI, imaging often underestimates the degree of brain
damage.
• Clinical outcome correlates inversely with the NAA/Cr ratio.
• The presence lactate or lipid indicates a worse prognosis.
42. 6) Alzheimer's disease
• Although MRS is not highly sensitive for detecting early Alzheimer's disease, as
the disease progresses, the spectrum becomes abnormal.
• With advancing disease the NAA is reduced and myoinositol becomes
elevated.
43. Alzheimer's disease cont..
• Myo-inositol is also increased in Down's syndrome, a dementia that
presents in childhood and is pathogenetically similar to Alzheimer's disease.
• On the other hand, it is not elevated in other adult dementia,
– so it is a helpful marker to distinguish Alzheimer's disease from the
other causes of dementia.
44. 6) Pediatric Metabolic Brain Disorders
• MRS has a very important role in diagnosing and monitoring
patients with metabolic disorders.
• list of diseases that affect the gray and white matter to varying
degrees
45. CANAVAN’S DISEASE
• Aspartoacylase deficiency
– key enzyme in myelin synthesis, with resultant accumulation of N-acetylaspartate (NAA) in the
brain
• leukodystrophy clinically cxd by megalencephaly, severe mental and neurological
deficits, and blindness
• Markedly elevated NAA and NAA:creatine ratio are pathognomonic (CaNAAvan)
