Brain metabolic mapping with MRS: A potent noninvasive tool for clinical diagnosis of brain disorders.

I am excited and honored to introduce this special issue on metabolic brain mapping of brain disorders in the American Journal of Neuroradiology. With the global extension of human life expectancy along with various lifestyle and environmental factors, there has been a dramatic increase in the incidence of various central nervous system disorders. These brain disorders with extremely different pathogeneses such as Alzheimer disease (AD), epilepsy, schizophrenia, major depressive disorder, bipolar disorder (BD), and so forth are affecting the quality of life of patients and having an economic impact on their families. The diagnosis is often very difficult and is based on the detection of clinical symptoms, which appear at relatively later stages in the pathogeneses. The efficacy and outcome of treatment regimens are, thus, contingent on diagnostic biomarkers that can facilitate early detection before the onset of clinical symptoms. There has been extensive research on developing surrogate markers for these disorders that can aid in disease detection, prediction of prognosis, treatment evaluation, and development of novel therapeutics. In recent years, neurochemical and metabolic profiling of the brain through molecular imaging tools like MR spectroscopy and positron-emission tomography have become increasingly important markers of CNS pathologies. PET is an extremely sensitive radionucleotide-based imaging technique that can determine the concentration of specific biomolecules in the picomolar range. With the continuing development of PET methodology and the ever-increasing number of biologically relevant molecular probes, PET has found clinical application in not only disease diagnostics but also drug development as a tool for tracking drug pharmacokinetics. Furthermore, PET imaging has enabled tracking of various crucial neurotransmitter systems. While PET uses radioligands injected in the bloodstream to image target macromolecules, MR spectroscopy is a noninvasive technique for investigating the biochemical profile of the brain without radioactive tracers. MR spectroscopy has been recently used in a number of clinical studies to supplement conventional MR imaging because it is able to provide the in vivo neurochemical profile of specific brain regions. H-MR spectroscopy detects several metabolites, including N-acetylaspartate, myo-inositol, choline, lactate, and so forth, in specific brain regions. Similarly, the P-MR spectroscopy technique can be used to obtain wellresolved peaks of inorganic phosphorus, phosphomonoester, phosphodiester, and phosphocreatine and to estimate pH levels. Furthermore, development of specialized editing sequences such as MEshcher-GArwood Point REsolved Spectroscopy (MEGA-PRESS) has enabled detection of crucial brain neurochemicals, such as glutathione, that are present at low concentrations. MR spectroscopy not only provides in vivo neurochemical characterization of brain pathologies detected by MR imaging, such as tumors, it is also a sensitive indicator of early disease pathology–induced metabolic alterations in brain regions appearing normal on conventional MR imaging. Various animal models and human clinical studies suggest that MR spectroscopy can help in differential diagnoses and can be important in monitoring the effects of therapeutic interventions and evaluating disease outcome. MR spectroscopy has evolved dramatically with the development of novel acquisition and analysis techniques, and it is a time-effective, accurate, and safe method for the estimation of various brain neurochemicals at high spatial resolution. This special issue offers a unique overview of studies that have used in vivo molecular imaging to assess the neurochemical alterations underlying various CNS disorders. Alzheimer disease is the most prevalent and debilitating neurodegenerative disorder, with current global World Health Organization estimates of approximately 36 million individuals. Gao and Barker reviewed the most up-to-date data attesting to the potential of H-MR spectroscopy as a biomarker for mild cognitive impairment (MCI) and AD. The authors reviewed the current methods used to collect MR spectroscopy data and outlined the findings of MR spectroscopy research in AD. They opined an invaluable role for MR spectroscopy as a predictive biomarker for the development of dementia and urged further evaluatory research in this regard. Kantarci provided a complementary review of the diagnostic value of amyloid-beta (A ) imaging with Pittsburgh compound-B PET in AD. The review highlighted the application of A imaging, especially in the differential diagnosis of AD. To assess the clinical applicability of molecular imaging techniques in disease diagnosis, one must compare and validate them with other neuroimaging and behavioral indicators of disease pathology. In an extensive multimodal cross-sectional neuroimaging study on the various structural and metabolic alterations in AD, Carter et al examined the extended medial temporal lobe memory network across the spectrum of disease severity from healthy controls to patients with MCI to AD. Their study assessed cognitive function, neurodegeneration with MR imaging morphometry, structural integrity with diffusion tensor imaging, and metabolic alterations with FDG-PET. The authors found significant correlations among fractional anisotropy decrease, gray matter volume, and metabolic alterations, indicating a close association among neurodegeneration, loss of structural integrity, and metabolic impairment, respectively. Molecular imaging has also proved helpful in tracking brain tumors, due to the unique alterations in their metabolic phenotypes. MR spectroscopy along with MR imaging for tumor classiIndicates open access to non-subscribers at www.ajnr.org