Emerging metabolic imaging and spectroscopic methods to study neurodegenerative diseases

Proton magnetic resonance spectroscopy (1H-MRS) allows non-invasive assessment of the metabolic landscape biological tissue. Despite demonstrating promising findings in clinical practice, single-voxel or single-slice two-dimensional 1H-MRS methods present a few challenges mainly related to limited spatial coverage and low spectral resolutions. In recent past, advent more sophisticated imaging spectroscopic sequences, such as three-dimensional echoplanar (3D-EPSI), correlation (2D-COSY), chemical exchange saturation technique (CEST) has revolutionized field metabolomics. For characterization diffused neurodegenerative diseases, whole brain is essential for comprehensive overview topography understanding underlying pathophysiological processes. The 3D-EPSI sequence acquisition (volumetric) metabolite maps with high resolution.1 These can be co-registered anatomical images facilitating mapping alterations from different regions single session, thus providing true extent global disease. potential 3D‐EPSI characterizing several neurological disorders been reported. On conventional one-dimensional 1H-MRS, peaks due methyl, methylene, methine protons N-acetyl aspartate, glutamate, glutamine, gamma-aminobutyric acid, taurine extensively overlap region 2-4 ppm, often confounding reliable detection quantification these metabolites. contrast, 2D-COSY offers unambiguous identification potentially overlapping resonances by dispersing multiplet structure scalar (J)-coupled spin systems into second dimension,2 especially at higher strength3,4 exploiting unlikely possibility that two metabolites would share identical shifts two-dimensions. Due technical limitations long time, not widely used study diseases. However, future modifications benefit implementing faster schemes improved fitting data analysis. We believe new approaches could make applications faster, easier, versatile. CEST relatively novel modality specific exogenous endogenous metabolites/molecules millimolar concentrations. Exchangeable solute functional groups amide (-CONH), amine (-NH2) hydroxyl (-OH) resonate frequency bulk water protons. labile are selectively saturated using radiofrequency irradiation, which subsequently transferred pool, leading decrease signal intensity proportional concentration molecules, number proton rate.5 than orders magnitude sensitivity compared detecting creatine, myoinositol mobile peptides.5 While transfer (APT) investigated various disorders, other techniques glutamate-CEST, creatine-CEST have performed only pre-clinical pilot studies newer developments will significant impact reshaping our biochemical profiles standardization harmonization parameters required fast-tracking implementation routine workflow.