The Essentials

MR spectroscopy is a non-invasive, radiation-free brain imaging technique that can be performed on any standard MRI scanner. Going beyond traditional imaging techniques, MR spectroscopy is used to analyze tissue metabolism, measuring metabolites at concentrations 10,000 times lower than conventional MRI. With proper analysis, this data can be used to form a ‘virtual biopsy’ of the brain, providing critical information about tissue composition without requiring a traditional surgical biopsy. This powerful technology has applications in patient populations with brain tumors, Alzheimer’s disease, Multiple Sclerosis and many other conditions.

Nuts and Bolts

The nuclei of many elemental isotopes (¹H, ¹³C, ¹⁹F and ³¹P, among others) have a characteristic spin, either ‘up’ or ‘down’, with one spin state higher in energy than the other. A spinning charge creates a magnetic field, and thus each elemental isotope has a unique magnetic moment. Within a given sample, the orientations of nuclear spin states are random. When placed in a large magnetic field, such as an MRI machine, however, the spin states all align with the field. With the application of energy—typically in the form of radio waves—a nucleus will flip from one spin state to the other. The frequency of energy that this flip requires is characteristic of the nucleus, but varies with the strength of the magnetic field and the electron shielding of other electrons in a molecule.

The output of MR Spectroscopy, therefore, is not a picture—as with the case with MRI—but rather a readout of resonances (peaks) as a function of frequency, expressed in parts per million. By reading these resonances, a spectroscopist can determine the chemical composition of a sample.   In vivo ¹H MR spectroscopy examines carbon bound protons in the 1-5 ppm range of the chemical shift scale. Metabolites typically assessed include lactate, NAA, glutamate, creatine, choline, and myo-inositol (Figure below). By analyzing the ratios of these metabolites, spectroscopist can use MR spectroscopy to diagnose and monitor progression in a variety of diseases—from tumors to traumatic brain injury.

The Metabolites

Lactate: Lactate is generally seen as a doublet (two peaks close together) at a frequency of 1.33 ppm. Again, healthy tissue does not have sufficient lactate to be detectable with MRS. However, CSF contains some lactate so that if the voxel is placed entirely in the ventricle, lactate may appear in the spectrum. Lactate, as a product of anaerobic glycolysis, is detected in diseased brain when oxygen starved. It is of great diagnostic value in cases of hypoxia, brain injury, and stroke. It is also elevated in some tumors where it is suggestive of aggressiveness as well as abscesses.

N-acetyl aspartate (NAA): At 2.0 ppm, NAA is an amino-acid derivative synthesized in neurons and transported along axons.  It is therefore a “marker” of viable neurons, axons, and dendrites27. The diagnostic value of NAA lies in the ability to quantify neuronal injury or loss on a regional basis and therefore, decreased NAA plays a diagnostic role in brain tumors, head injury, dementias, and many other neurological disorders in which neuronal loss is expected.  Increased NAA is observed only in recovery and in Canavan disease that is due to a specific genetic disorder that reduces NAA-deacyclase activity resulting in net accumulation of NAA.

Glutamate—Glutamine—Gamma-amino butyrate (Glx): A mixture of closely related amino acids, amines and derivatives involved in excitatory neurotransmission lie between 2.1 and 2.4ppm. Glx is a vital marker(s) in MRS of stroke, lymphoma, hypoxia, and many metabolic brain disorders.

Creatine (Cr): The primary resonance of creatine lies at 3.0ppm. It is the central energy marker of both neurons and astrocytes and remains relatively constant. For that reason, it is often used as an internal reference for comparison to other metabolites. While some studies have found Cr reduced, it is only in inborn errors of metabolism that significant reductions of Cr occur.

Choline (Cho): Choline includes several soluble components of brain myelin and fluid-cell membranes that resonate at 3.2ppm. 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.

Myo-inositol (mI): A little known polyol (sugar-like molecules) that resonates at 3.6ppm, mI is mostly a diagnostic “modifier” in those diseases that affect Cho (tumor, MS, etc). As an astrocyte marker and osmolyte, mI contributes specificity in dementia diagnoses106, and an almost absolute specificity to hepatic encephalopathy and hyponatremic brain syndromes.

Additional resonances: A number of additional brain metabolites can be measured with MRS, such as gamma-amino butyric acid (GABA), scyllo-inositol, glutathione, etc.; however, specialized editing sequences or additional software is required to detect and measure them and, therefore, they are beyond the scope of typical clinical practice. However, as MRS methods mature, they may soon be available to clinicians for assaying.

(From Brigham and Women’s Center for Clinical Spectroscopy)