The electromagnetic radiation produced by any substance is dependent on its atomic composition. Spectroscopy is the determination of this chemical composition of a substance by observing the spectrum of electromagnetic energy released from chemical sample or a tissue.
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is the name given to a technique which exploits the magnetic properties of certain nuclei. This phenomenon and its origins are detailed in a separate section on nuclear magnetic resonance. The most important applications for the organic chemist are proton NMR and carbon-13 NMR spectroscopy. In principle, NMR is applicable to any nucleus possessing spin.
Initial NMR experiments were done by Rabi and co-workers in 1938. These efforts were acknowledged by the Nobel Prize in 1944. Later Purcell and Bloch (1952) first detected NMR signals from magnetic dipoles of nuclei when placed in an external magnetic field. The first NMR imaging was performed in 1970 on animals followed by human application developed by Dr. Damadian in 1980, who introduced the first commercial MRI scanner. Parallel to the introduction of magnetic resonance imaging (MRI) to clinical practice, initial in vivo brain spectroscopy studies were done in the early 1980s. Magnetic resonance spectroscopy (MRS) has rapidly progressed in its clinical utility and recognition. Today, MRS has become a significant no-invasive diagnostic tool and has gained wide clinical acceptability.
MRS can be performed by two methods–single-voxel spectroscopy (SVS), where a single sample volume is selected and a spectrum obtained from it, or multi-voxel spectroscopy where spectra are obtained from multiple voxels in a single slab of tissue. SVS gives a better signal-to-noise ratio and is a more robust technique. The disadvantage is that only a single spectrum is obtained. The placement of the volume of interest (VOI) becomes critical and may lead to errors of interpretation if not done correctly. With multi-voxel MRS, a much larger area can be covered, eliminating the sampling error to an extent. This however is done at the expense of a significant weakening in the signal-to-noise ratio and a longer scan time. Both SVS and multi-voxel imaging utilize specialized MR pulse sequences. The two most widely used are the Point Resolved Excitation Spin-echo Sequence (PRESS) and the STimulated Echo Acquisition Mode (STEAM) technique. Details of both these techniques are beyond the scope of this article.
Brain Metabolites Identified with MRS
MRS provides biochemical information of compounds present in human tissue and cells. Human brain contains hundreds of metabolites but proton MRS can only detect a few of them as least mulli-molar concentrations are necessary for the metabolites to be detected. The major brain metabolites detected are choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, myo-inositol, glutamine and glutamate, lipids, and the amino acids leucine and alanine.
N-Acetyl Aspartate (NAA) is an amino acid found exclusively in neurons. It is regarded as a non-specific marker and is thought to be involved in Coenzyme A interactions and lipogenesis within the brain. It is a marker of neuronal viability. Normal NAA concentration is in the range of 8-9 mmol/kg in healthy adult brain. Concentrations are decreased in conditions leading to axonal injury or neuronal loss. NAA is also decreased in other conditions such as neoplasm, infarction, and inflammatory conditions such as multiple sclerosis. NAA peak is seen at 2.0 ppm (parts per million) on MR spectra.
The Choline (Cho) peak is a heterogeneous peak representing various choline-containing compounds such as acetylcholine, phosphocholine (lecithin), glycerophosphocholine, and various other intermediates of phospholipids metabolism. It is an indicator of cell density and cell wall turnover. Elevated levels are found tumors, especially malignant ones, and in certain demyelinating diseases. Choline resonance presents at 3.22 ppm. Studies have shown there is also a direct association between Cho and levels of Ki-67, a protein expressed in all phases of the cell cycle except GO that serves as a good marker for cellular proliferation. This observation makes Cho a reliable predictor of cellular activity in tumor tissue.
Creatine (Cr) is basically related to cell energy pathways. It is both the substrate and product of creatine kinase. Creatine reflects the energy potential available in brain tissue. Its concentration in normal brain remains very high and stable due to high metabolic energy needs of brain cells. Its peak is noticed at 3.0 ppm. Creatine-Choline ratios are an important indicator of disease states such as demyelization.
Lactate (Lac) is absent in normal brain tissue and its presence is indicative of anerobic glycolysis at the cellular level. Elevated levels are associated with ischemic conditions or metabolic disorders (where anerobic glycolysis predominates) but is also noted at the edges of large brain tumours. The peak is very sensitive to the technique employed and unless the correct echo time is employed, it may be artifactually suppressed. The spectral peak lies at 1:33 ppm. The peak is often inverted or bifid.
Lipid is also absent normally but can increase in tumors, infections or metabolic conditions. The peak is at 1.3 ppm and it overlaps with lactate peak.
Myo-inositol (Ins) is a naturally occurring sugar. It is the dominant peak in newborn brains and lies at 3.56/4.06 ppm. It is regarded as an astrocytic marker and is a possible marker for intracellular osmotic integrity. Its concentration is decreased in stroke, tumours, lymphoma and some low -grade malignancies.
Glutamate/Glutamine/GABA are neurotransmitters and act as markers for neuronal-glial interaction. Peaks lie at 2-2.5 and 3.4-3.7 ppm.
Magnetic Resonance Spectroscopy Publication References
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