differentiating different brain lesion using MR Spectroscopy which is a newer MR technique to quantify different metabolites present within the lesion and adjacent parenchyma

1. Case Discussion
Dr. Yasna Kibria
Phase B resident
Department of Radiology and Imaging
BSMMU

10. Magnetic Resonance Spectroscopy
Basic Physics and Clinical Applications

11.  Magnetic Resonant spectroscopy (MRS) allows
tissue to be interrogated for the presence and
concentration of various metabolites
 It does not add a great deal to an overall MR study
but does increase specificity, and may help in
improving our ability to predict histological grade
 MR spectroscopy provides a measure of brain
chemistry
 MR spectroscopy is the use of magnetic
resonance in quantification of metabolites and
the study of their distribution in different tissues
 Rather than displaying MRI proton signals on a
gray scale as an image, depending on its relative
signal strength, MRS displays the quantities as a
spectrum
 The resonance frequency of each metabolites is
represented on a graph and expressed as parts
per million(ppm)

18. The horizontal axis represents the
frequencies (chemical shifts-ppm)
and the vertical axis represents the
concentration of the metabolites

20. How to obtain quality spectra ?
 Appropriate shimming to improve field
homogeneity
 Adequate water suppression by CHESS
 Adequate voxel adjustment to avoid :
 Bones
 Metals
 Blood vessels
 Blood products
 Air, CSF, fat
 Necrotic areas
 Calcifications

21. Choosing Spectroscopic Technique:
a) Single Voxel Spectroscopy (SVS)
b) Multi voxel spectroscopy
Single Voxel MR Spectroscopy Multi Voxel MR Spectroscopy
Less advanced More advanced technique
Less spatial resolution More spatial resolution
Volume averaging Less volume averaging
Short acquisition time Long acquisition time
For simpler & smaller volume of tissue For larger volume of tissue
Fixed grid Grid may be shifted after acquisition

22. Spectroscopic technique
Four methods commonly used for localization in clinical practice:
STEAM (Stimulated echo acquisition method)- three 90 degree
excited pulse applied along three planes. Short TE (20ms) is used.
PRESS (point resolved spectroscopy)- one 90 degree and two 180
degree pulse are applied along three planes. longer TE (270ms) is
used.
DRESS- depth resolved surface coil spectroscopy.
CSI- chemical shift imaging method.

23. Selection of MRS parameters
• TR & TE are important parameters
• Improved SNR is obtained at longer TR
• TEs commonly used are 20-30ms,135-145ms &
270ms
• At longer TEs more than 135ms- peaks of major
brain metabolites are visible
 Long TE:
Choline(cho)
Creatine(cr)
N-acetyl aspartate(NAA)
Lactate
 Short TE-
Myoinositol
Glutamate
Glutamine
Glycine
Lipid

25. ppm Metabolites Properties
2.02 NAA Neuronal marker
3.22 Choline Cell membrane marker
3.02 Creatine Energy metabolism
3.5 Myo-inositol Glial cell marker
0.9-1.4 Lipid Products of brain cell
destruction
1.3 Lactate Product of anaerobic
glycolysis
Major Brain metabolites

26. N-Acetylaspartate (NAA)
NAA = neuronal health
Seen at 2.02 ppm
Marker of neuronal & axonal viability
and density
Exclusively found in CNS, both grey &
white matter
Higher peaks = normal neuronal
presence
Diminished peaks = neural damage or
replacement has occurred
Decreased in:
Malignant diseases
Neurodegenerative
diseases
Hypoxia
Stroke
Demyelination
Epilepsy
Hypoxia
Trauma
Increased in-
Canavan's disease
Absent in extra axial lesions
(tissue with no neuron)-
Meningioma
Lymphoma
Metastasis from outside the
brain

27. Choline (Cho)
Seen at 3.22 ppm
Peak represents a combination of
choline & choline-containing
compounds
Marker of cellular membrane
turnover reflecting cellular
proliferation
In tumor, cho levels correlate with
degree of malignancy reflecting
cellularity
Elevated cho is nonspecific
•Increased in-
 Gliomas ,infarction, hypoxia,
Alzheimer’s disease, epilepsy, head
trauma
 Also elevated in developing brain
•Decreased in-
hepatic encephalopathy

28. Creatine(Cr)
• Peaks at 3.02 ppm
• Peak represents combination of creatine &
phosphocreatine
• Marker of energetic systems and intracellular
metabolism
• Concentration of creatine is relatively
constant(most stable metabolite)
• Used as an internal reference for calculating
metabolic ratios
• Renal diseases may affect Cr levels in the brain

29. Lactate(Lac)
 Doublet at 1.33 ppm
 Peak is inverted at TE -144ms which
helps to distiguish lactate from lipids
 Not seen in normal brain spectrum
 Product of anerobic glycolysis
 Increases under anaerobic
metabolism
Cerebral hypoxia, ischemia, IC
hemorrhage, stroke
Metabolic disorders (especially
mitochondrial ones)
Macrophage accumulation (e.g. acute
inflammation)
Tissues with poor washout (cysts,
necrotic & cystic tumors, NPH)

30. Lipid(Lip)
Two peaks of lipid at 1.3 and 0.9 ppm
Lipids are components of cell membrane not
visualized on long TE
Absent in normal brain
Presence of lipid may result from improper voxel
selection- contamination by subcutaneous fat
from the skull
Increased in high grade tumors (reflect necrosis),
stroke, multiple sclerosis, tuberculoma, abscess
etc

31. Myoinositol (Myo)
Decreased in-
Hepatic and hypoxic encephalopathy
Osmotic pontine myelinolysis

35. The three-steps approach to spectral analysis
Step 1: The quality assurance phase. Is it an adequate spectrum?
Step 2: Is Hunter's angle normal?
Step 3: Starting from the right side of the graph, count off the location
and check quantities of The Good (NAA=2.02ppm), The Bad(Cho=3.22),
and The Ugly(LL=0.9-1.33ppm).

36. Hunter's angle
Neurosurgeon, Hunter Sheldon, at Huntington Medical Research Institutes.
Instead of doing complex ratios and analysis of the spectra, he simply used his
pocket comb. He placed his comb on the spectrum at approximately a 450 angle
and connected several of the peaks. If the angle and peaks roughly
corresponded to the 450 angle, the curve was probably normal
If the peaks strayed off the comb's angle, the curve was abnormal. This is a
quick, useful method to read MRS and determine normal from abnormal
It is important to remember, however, that this angle was used with STEAM
spectra from the brain

37. 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
CLASS-B APPLICATIONS :
(Occasionally useful in individual Patients)
• Ischemia, Hypoxia and Related Brain Injuries
– Acute Ischemic stroke
– Cardiac arrest and global hypoxia
– Hypoxia- Ischemia in Neonates
• Epilepsy
CLASS-C APPLICATIONS :
(Useful Primarily in group of patients-research)
• Neuro-AIDS
• Opportunistic Infections
• Neurodegenerative diseases –
– Alzheimer’s disease
– Parkinson’s disease and plus syndromes, ALS, MS, HD
• Hepatic encephalopathy
• Traumatic Brain injury (DAI)
• Psychiatric disorders

38. APLICATIONS OF MRS IN BRAIN TUMOURS
• The evaluation of brain tumors is one of the areas where MRS
has impacted patient management
• MRS can provide information on some of the key clinical
questions:
Diagnosis
Tumor grading
Distinguishing primary CNS neoplasm from metastasis
Therapeutic planning
Prognosis
Therapeutic response & progression

39. • MRS must always be interpreted within the context of the other available imaging
information (T1, T2, post contrast imaging, diffusion, & perfusion)
• The degree of Cho elevation depends on the metabolic activity of the neoplastic cell and
the proportion of neoplastic relative to normal cells within the VOI
• The typical H+-MR spectrum of a neoplasm
Substantial elevation of Choline
A reduction of NAA
Little or minor changes in Creatine
NAA/Creatine – decrease
Choline/Creatine- increase in respect to
normal brain parenchyma
Lactate peak- if necrosis
ICSOLs

40.  A Cho/NAA ratio > 1.3 - reported to have a
high accuracy for detection of neoplasm
High Cho/NAA & Cho/Cr ratio : strong
indicator of a higher-grade neoplasm
 But a low Cho/NAA ratio could arise from:
– low-grade neoplasm
– low neoplastic cellular density
– Non-neoplastic processes such as multiple sclerosis
Choline peak-
Higher in centre of a solid tumor
Consistently low in necrotic areas

41. •Astrocytomas are classified as low grade
benign & high grade malignant tumors
•High grade gliomas include anaplastic & GBM
High Grade Glioma Vs Low Grade Glioma
 Higher Cho
 Lower NAA
 Higher Cho/Cr, Cho/NAA
 Threshold value of 2.0 for Cho/Cr
High grade
Glioma

46. Well-differentiated astrocytoma, we would
expect to see an elevated myoinositol to
creatine ratio:
0.8 in low-grade astrocytomas
0.3 in anaplastic astrocytomas
0.15 in GBM

47. The NAA : Cr ratio is low and the Cho : Cr ratio is high. A myoinositol peak at 3.6 ppm is noted.

48. PRIMARY CNS NEOPLASM VS METASTASIS
•As primary neoplasm infiltrates surrounding brain tissues & Mets
shows sharp margins, interrogation of areas outside the
enhancing portion of the lesion has proved to be more promising
•Various metabolites have been suggested for this purpose , in
one study Cho/NAA > 1 has an accuracy of 100% being a
neoplasm

49. •Theoretically NAA shouldn't be present
•But presence of it indicate voxel contamination
•Alanine is characteristic of meningeal tumors, but is not always
present
•Alanine doublet at 1.4 ppm
•Lactate peak at 1.3 ppm
•Mobile lipids and high Cho are associated with aggressive
tumors
•Myo-inositol helps to distinguish hemangiopericytomas from
meningioma
MENINGIOMA

51. ABSCESS
•The metabolites important in CNS infections are amino acids (valine,
leucine, and isoleucine, 0.9 ppm), alanine (1.48 ppm), acetate (1.92
ppm), succinate (2.4 ppm), glycine (3.56 ppm), and trehalose (3.6-3.8
ppm)
•The presence of amino acids usually differentiates from tumors
•Magnetic resonance spectroscopy is diagnostic in pyogenic
abscesses
•Elevation of a succinate peak is relatively specific but
not present in all abscesses
•High lactate, acetate, alanine, valine, leucine, and
isoleucine levels peak may be present
•Cho/Cr and NAA peaks are reduced
•Trehalose, if seen, is specific for fungal infections.

54. TUBERCULOMA
•Decrease in NAA/Cr
•Slight decrease in NAA/Cho
•Lipid-lactate peaks are usually elevated (86%)
•Absence of amino acid peak helps to discriminate
pyogenic from tubercular abscess