Citation, DOI & article data
The technique of magnetic resonance spectroscopy (usually shortened to MR spectroscopy or MRS) allows tissue to be interrogated for the presence and concentration of various metabolites. Grossman and Yousem said "If you need this to help you, go back to page 1; everything except Canavan (disease) has low NAA, high choline" 1. This is perhaps a little harsh, however, it is fair to say that MRS often 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.
The basic principle that enables MR spectroscopy (MRS) is that the distribution of electrons within an atom cause nuclei in different molecules to experience a slightly different magnetic field. This results in slightly different resonant frequencies, which in turn return a slightly different signal. The technique is identical to that of nuclear magnetic resonance (NMR) as used in analytical chemistry, but the community commonly refers to in vivo NMR as MRS to avoid confusion (and, arguably, the word "nuclear").
MR spectra can be acquired from any "NMR-active" nucleus, which is a nucleus possessing non-zero spin: protons, carbon-13 and phosphorus-31 are the most commonly encountered, and in clinical practice essentially only proton spectra (which enable the resolution of metabolite profiles in vivo) are encountered. Phosphorus-31 (P-31) is typically used to look at the ratio of adenosine triphosphate (ATP) to phosphocreatine and other metabolites, and can be used to assess the energy charge of the cell.
If raw signal was processed then the spectra would be dominated by water, which would make all other spectra invisible. Water suppression is therefore part of any MRS sequence, either via inversion recovery or chemical shift selective (CHESS) techniques. If water suppression is not successful then a general slope to the baseline can be demonstrated, changing the relative heights of peaks.
Magnetic resonance spectroscopy (MRS) is performed with a variety of pulse sequences. The simplest sequence consists of a 90 degree radiofrequency (RF) pulse, without any gradients, with reception of the signal by the RF coil immediately after the single RF pulse.
Many sequences used for imaging can be used for spectroscopy also (such as the spin echo sequence). The important difference between an imaging sequence and a spectroscopy sequence is that for spectroscopy, a read-out gradient is not used during the time the RF coil is receiving the signal from the person or object being examined. Instead of using the frequency information (provided by the read-out or frequency gradient) to provide spatial or positional information, the frequency information is used to identify different chemical compounds. This is possible because the electron cloud surrounding different chemical compounds shields the resonant atoms of spectroscopic interest to varying degrees depending on the specific compound and the specific position in the compound. This electron shielding causes the observed resonance frequency of the atoms to slightly different and therefore identifiable with MRS.
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.
- lipids: resonates at 1.3 ppm
- lactate: resonates at 1.33 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
- creatine (second peak): resonates at 3.95 ppm 10
- lactate quartet: resonates at 4.11 ppm
NB: ppm = parts per million
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.
May be difficult but in general non-glial tumors will have little, if any, NAA peak.
Distinguishing radiation change and tumor recurrence can be problematic. In recurrent tumor choline will be elevated, whereas in radiation change, NAA, choline and creatine will all be low.
Ischemia and infarction
Lactate will increase as the brain switches to anaerobic metabolism. When infarction takes place then lipids are released and peaks appear.
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 myo-inositol
- Canavan disease characteristically demonstrates elevated NAA
Markedly reduced myo-inositol, and to a lesser degree choline. Glutamine is increased.
- Leigh syndrome: elevated choline, reduced NAA and occasionally elevated lactate
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 Paul A Bottomley 9.
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