MR spectroscopy (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 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 around 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. 31P 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). If water suppression is not successful then a general slope to the base line 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.
- lactate: resonates at 1.3 ppm
- lipids: resonates at 1.3 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 4.4 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 tumours will have little, if any, NAA peak.
Distinguishing radiation change and tumour recurrence can be problematic. In recurrent tumour choline will be elevated, whereas in radiation change, NAA, choline and creatine will all be low.
Ischaemia 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 myoinositol
- Canavan disease characteristically demonstrates elevated NAA
Markedly reduced myoinositol, 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: Myoinositol 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.
- 1. Grossman RI, Yousem DM. Neuroradiology, the requisites. Mosby Inc. (2003) ISBN:032300508X. Read it at Google Books - Find it at Amazon
- 2. Al-okaili RN, Krejza J, Wang S et-al. Advanced MR imaging techniques in the diagnosis of intraaxial brain tumors in adults. Radiographics. 2006;26 Suppl 1 : S173-89. doi:10.1148/rg.26si065513 - Pubmed citation
- 3. Qayyum A. MR spectroscopy of the liver: principles and clinical applications. Radiographics. 2009;29 (6): 1653-64. doi:10.1148/rg.296095520 - Pubmed citation
- 4. Huang W, Alexander GE, Daly EM et-al. High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: a 1H MRS study. Am J Psychiatry. 1999;156 (12): 1879-86. Am J Psychiatry (link) - Pubmed citation
- 5. Bradley WG, Bydder GM. Advanced MR imaging techniques. Informa HealthCare. (1997) ISBN:1853170240. Read it at Google Books - Find it at Amazon
- 6. Choi C, Ganji SK, DeBerardinis RJ et-al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat. Med. 2012;18 (4): 624-9. doi:10.1038/nm.2682 - Free text at pubmed - Pubmed citation
MR spectroscopy (MRS)
- Hunter's angle
- lactate peak: resonates at 1.3 ppm
- lipids peak: resonate at 1.3 ppm
- alanine peak: resonates at 1.48 ppm
- N-acetylaspartate (NAA) peak: resonates at 2.0
- glutamine-glutamate peak: resonate at 2.2-2.4 ppm
- gamma-aminobutyric acid (GABA) peak: resonate at 2.2-2.4 ppm
- citrate peak: resonates at 2.6 ppm
- creatine peak: resonates at 3.0 ppm
- choline peak: resonates at 3.2 ppm
- myo-inositol peak: resonates at 3.5 ppm