We describe the details of the magnetic resonance spectroscopy and chemical shift imaging techniques for the human brain which have been developed over the last two decades. With these non-invasive tools, it is now readily possible to repeatedly assay up to 20 common brain metabolites. From the perspective of drug discovery, each of these metabolites could fulfill a number of useful functions: disease biomarker, surrogate marker of drug delivery, surrogate marker of drug efficacy and so on. To facilitate the possible utility of clinical magnetic resonance spectroscopy in future drug discovery, the major portion of the review is devoted to a detailed description of the well-validated neurochemical profiles of many common human brain disorders, for which MRS data now exists. Beyond proton, MRS, the commonest tool provided by the manufacturers of clinical MRI equipment, lays the world of heteronuclear NMR more familiar to chemists. Here too, with relatively little effort it has been possible to define neurochemical profiles of human brain disorders using 13C MRS. The future for drug discovery scientists is discussed. Finally, recognizing that a known feature of MR is the lack of sensitivity, we describe new efforts to harness hyperpolarization, with its 50,000 signal amplification, to conventional MRS.
Keywords: Spectroscopy, metabolites, biomarkers, drug discovery, MR spectroscopy, MRS, molecular imaging, Positron Emission Tomography, PET, neurospectroscopy, ISIS, PRESS, STEAM, CSI, nuclear Overhauser effect, NOE, N-Acetylaspartate, NAA, Creatine, Phosphocreatine, Myo-Inositol, Scyllo-Inositol, astrocytes, pseudodementia, Hepatic encephalopathy, transient ischemic attack (TIA), MELAS, mitochondrial encephalopathy with lactic acidosis, Neonatal hypoxia, Closed Head Trauma, Closed head injury, traumatic brain injury, Toxoplasmosis, CNS lymphoma, progressive multifocal leukoencephalopathy, Cryptococcoma, cytochrome P4502D6, CYP2D6, P-glycoprotein efflux transport, receptor imaging indicators