differentiating different brain lesion using MR Spectroscopy which is a newer MR technique to quantify different metabolites present within the lesion and adjacent parenchyma
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)
12.
13.
14.
15.
16.
17.
18. The horizontal axis represents the
frequencies (chemical shifts-ppm)
and the vertical axis represents the
concentration of the metabolites
19.
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
24.
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
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
42.
43.
44.
45.
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
50.
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.
52.
53.
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
Editor's Notes
In this case our impression was MRI & MRS findings consistent with high grade glioma involving
First of all, from the spectroscopy of this patient we can appreciate that voxel acquisition & adjustment was not properly done. WE actually couldn’t measure the spectrum from the solid portion of the lesion. However , we set the voxel adjacent to the solid part it produced this spectrum
If we set the voxel over the perilesional area , it produces a spectrum like this which is almost a normal spectrum.
Our impression MRI & MRS consistent with intracranial hemorrhagic metastasis.
We can see in bth cases MRS along with MRI helped us to specify the pathology
X axis represents chemical shift(frequency/ppm).
Y axis(area under the peak) represents intensity which is proportional to concentration of metabolite/nucleus.
A good quality spectrum should represent a flat horizontal baseline with distinct narrow peak
Isolated & typically identical proton will give a single peak known as singlet.sometimes protons are close enough their mag spin state interact with each other known as spin-spin coupling.if pro A has neighbouring pro B with diff chemical environ , pro A will be affected by pro B & produce a doublet. 2 neighbouring pro
Myo is high in low grade glioma & it decreases with increasing grades of the tumor
Glioma edge cant be indicated by any kind of imaging.The edges are diffuse through the brain parenchyma.
It means mets have a well detectable margin. So we couldn’t be distinguish primary from 2ndary if we set the voxel in intratumaral portion as they indicate similar tumor spectrum.we have to set the voxel over peritumoral area to differentiate these two.
Pyogenic abscess in the right parieto-occipital region Axial T2WI shows a well-defined hyperintense lesion with a hypointense wall and perifocal edema. B, The lesion appears hypointense on the axial T1WI with an isointense wall. C, Postcontrast T1WI shows ring enhancement. D, spectroscopy from the center of the lesion shows resonances of AAs, 0.9 ppm; Lip/Lac, 1.3 ppm; Ac, 1.9 ppm; and Suc, 2.4 ppm.
Hyperintense core shows Lip/Lac with no evidence of Cho & AA.
Axial post C T1WI on follow-up MRI, show areas of irregular contrast enhancement at site of prior resection ependymoma resected from left frontal lobe (A). Two-dimensional chemical shift image shows pathologic spectra with increased Cho/NAA and Cho/Cr ratios and a decrease in the NAA/Cr ratio, those are consistent with tumor recurrence