MR Spectroscopy in Brain Cancer
Brain Cancer

Author: Gianpiero Pescarmona
Date: 26/03/2009


Routine neuroimaging centers are confined to automated or ready-made method of MRS, nevertheless, have found sufficient diagnostic information in proton (1H) MRS, which defines fewer than 15 brain metabolites. 1H MRS and routine MRI share the same radio-frequency range (and hence need no expensive upgrades to the MR scanner) and is therefore cost effective and expeditious.


When analyzing and reporting MRS, it is important to read and record all peaks in the spectrum. We found the following mnemonic to be quite useful: Lying, Lazy No Good Crooks C(h)ollected My Insurance for right to left: lipids, lactate, N-acetylaspartate (NAA), glutamate/glutamine (Glx), creatine (Cr), choline (Cho), and myo-inositol (mI), respectively (FIG. 1).


Lipids are broad peaks that occur at 0.9 and 1.2 parts per million (ppm). In healthy tissues, there should be very little lipid in the spectrum unless the area includes subcutaneous fat from the skull. The presence of lipid can have diagnostic value in brain tumor where lipid indicates necrosis.5 In this extreme setting, a third lipid peak, at 2 ppm may displace or mask the normal NAA resonance.


Lactate is generally seen as a doublet (two peaks close together) that has a frequency of exactly 1.33 ppm. Again, healthy tissue does not have sufficient lactate to be detectable with MRS. CSF contains lactate at about 1 mm so that if the voxel is placed entirely in the ventricle lactate will appear in the spectrum (a potential source of error when examining patients with hydrocephalus). Lactate as a product of anaerobic glycolysis is detected in diseased brain, which is oxygen starved in stroke, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke, recovery from cardiac arrest, neonatal hypoxia, etc. It is of greatest diagnostic value in cases of brain injury or trauma where hypoxia is part of the differential. It is also a nonspecific marker of tumor aggressiveness ( or better of tumor hypoxia when angionesis dont supply enough vessels for cell growth) and is found in cysts and abscesses of all types.5

N-acetyl aspartate

At 2.0 ppm, NAA is an amino acid derivative synthesized in neurons and transported down axons. It is therefore an almost 100%-specific marker of viable neurons, axons, and dendrites ( in which the axonal transport is working properly ). The diagnostic value of NAA lies in the ability to quantify neuronal injury or loss on a regional basis.

Glutamate-glutamine (Glx)

A mixture of closely related amino acids, amines and derivatives closely involved in excitatory and inhibitory neurotransmission that lies between 2.1 and 2.4 ppm. Because these are also integral products of intact TCA (Krebs) cycle activity and mitochondrial redox systems, Glx offers a vital marker(s) in MRS of stroke, lymphoma, hypoxia, and many metabolic brain disorders. ( As a matter of fact glutamate (a neurotransmitter) and glutamine (an essential metabolite for DNA synthesis) have a different metabolism. Glutamate is high in oxygen and in healthy neuron like NAA. Glutamine is high in Glia (that is able to proliferate) and in hypoxia. Both (Glx) are synthesized from glucose and therefore sign of high glucose supply or poor glucose degradation )


The primary resonance of creatine lies at 3.0 ppm. As phosphocreatine, it is the central energy marker of both neurons and astrocytes. A “constant” in the normal brain spectrum, the Cr peak intensity thereby standardizes its interpretation. Metabolite/Cr peak height ratios are astonishingly reproducible and a visual pattern described by Hunter's angle (HA), can be relied upon for radiological interpretation of almost all pathological spectra. ( Creatine is assumed to be constant in neuronal cell but should be higher where the the number of the cells is higher than those of axons ).


Cho [sometimes designated trimethylamine (TMA)] is an umbrella term for several soluble components of brain myelin and fluid-cell membranes that resonate at 3.2 ppm. Because by far the majority of choline-containing brain constituents are not normally soluble, pathological alterations in membrane turnover ( tumor, leukodystrophy, multiple sclerosis ) result in a massive increase in MRS-visible Cho, providing a diagnostic gold mine.


A previously little-known polyol (sugar-like molecules) that resonates at 3.6 ppm, mI is the missing osmolyte of the early neurological literature for brain volume regulation. In neurospectroscopy, mI is mostly a diagnostic modifier in those diseases that affect Cho (tumor, multiple sclerosis, etc). As an astrocyte marker and osmolyte, mI contributes specificity in dementia diagnosis and adds specificity to monitoring hepatic encephalopathy and hyponatremic brain syndromes. ( inositol synthesis is reduced in hypoxia, ethanol abuse, diabetes; It is released from the membranes upon agonist binding to a specific receptor. Any cell damage can increase the amount of free (visible) myo-inositol )

High-resolution magic angle spinning magnetic resonance spectroscopy detects glycine as a biomarker in brain tumors.
Int J Oncol. 2010 Feb;36(2):301-6.
Righi V, Andronesi OC, Mintzopoulos D, Black PM, Tzika AA.

NMR Surgical Laboratory, Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.

The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients undergoing surgery for epilepsy, we tested the hypothesis that the presence of glycine may distinguish among these brain tumor types. Using high-resolution magic angle spinning (HRMAS) 1H magnetic resonance spectroscopy (MRS), we determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly signals from overlapping myo-inositol (Myo) signals and tested our methodology in phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly in tumor biopsies (all combined) relative to controls; Gly levels were significantly elevated in LG, MT and GBM biopsies (P<or=0.05). Residual Myo levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control levels). We observed higher levels of Gly in GBM as compared to LG tumors (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ significantly from each other, the Gly:Myo ratio did distinguish GBM from MT (P<0.003) and from all other groups, a distinction that has not been adequately made previously. We conclude from these findings that Gly can serve as a biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for brain tumor classification.

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