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Making the 'virtual biopsy' a reality with MR spectroscopy

From the November 2018 issue of DOTmed HealthCare Business News magazine

By Dr. Alexander Lin

Magnetic resonance spectroscopy provides a “virtual biopsy” by measuring the concentrations of chemicals in the brain in a completely safe and noninvasive manner using standard MR equipment.
Changes in brain chemistry provide insight into pathophysiological changes that highly complement MR diagnoses.

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To date there are over 28,000 publications that detail the use of MR spectroscopy for a wide range of neurological disorders, however, this promising technique has not been fully utilized in clinical practice. Recent advances in technology are addressing these issues to translate MR spectroscopy from the benchtop to the bedside.

MR spectroscopy is ideally suited for repeated measurements and for measuring therapeutic outcomes by obtaining chemical signals, or metabolites, from a region of interest. A spectrum of peaks is generated whereby each peak is reflective of a chemical that resonates at a specific frequency (described in parts per million or ppm); the height of the peak reflects the concentration of that chemical in the brain (described as a ratio to creatine, institutional units, or millimolar concentration).

Brain metabolites
Different metabolites can be detected with MR spectroscopy and their biological roles can be used to provide pathophysiological insight for diagnosis and treatment monitoring.

The major metabolites include N-acetyl aspartate (NAA) which can be used to monitor neuronal health; choline (Cho), which indicates membrane turnover and can be used to assess tissue damage due to brain injury or cancer; measures of total creatine (Cr), which can be used as an energy marker although in most cases serves as an internal reference; myo-inositol (mI) is an osmolyte and astrocytic marker. More recently, MR spectroscopy has been shown to measure 2-hydroxyglutarate (2HG), an oncometabolite – a highly specific marker of cancer.

Glutamate (Glu, which is often indistinguishable from glutamine, they are frequently quantified jointly as Glx) is an excitatory neurotransmitter that is often modulated by disease and treatment; lactate (Lac), a marker of hypoxia; and glutathione (GSH), an anti-oxidant whose levels may reflect neuro-inflammation can be also measured but require specialized post-processing tools.

Clinical utilization
Different neurological disorders affect different brain metabolites differently. Every metabolite has a "normal" concentration that generates a pattern of peaks that is the same from person to person unless there is an underlying pathology. Diagnosis with MR spectroscopy can therefore be made by either comparing the numeric values of metabolite concentrations or by recognizing abnormal patterns of peaks in the spectra, such as in ECG interpretations.
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