The boxes … High field MR spectroscopy with protons Neurochemical profiling in the animal brain Proton (ie, 1H) MRS, based on the proton resonance of hydrogen atoms, received considerable amount of attention in biomarker studies of neurological and psychiatric diseases80 because it enables noninvasive detection of a number of endogenous small molecular weight neurochemicals directly in affected brain regions (eg, see detailed reviews in refs 81-83). Depending on the Sotrastaurin purchase acquisition parameters,

up to five neurochemicals can be quantified reliably from human brain at 1.5 T. Animal model studies at Inhibitors,research,lifescience,medical very high magnetic fields, where spectral resolution and sensitivity are enhanced, were critical in demonstrating the feasibility of going beyond this. Early studies employed animal brain tissue extracts at high-field MR instruments demonstrating the wealth of biochemical information available

by MRS.84-87 With recent advances in high-field MR Instrumentation, spectroscopy localization techniques and sophisticated spectral quantification methods, however, the sensitivity Inhibitors,research,lifescience,medical and resolution of in vitro MRS was approached in the in vivo animal and human brain.83 Ten to fifteen neurochemicals in the human brain88,89 and up to eighteen neurochemicals in the rat brain90 can now be quantified noninvasively Inhibitors,research,lifescience,medical by high field MRS. In the mouse, which is highly desirable because of the availability of many models of human diseases, measurement of a 16-component neurochemical profile from 5-10 L volumes has been feasible.91 The mouse brain studies encounter major Inhibitors,research,lifescience,medical challenges in MR instrumentation and methodology.85,92 However, these difficulties were overcome in the last decade. The ability to measure an extended “neurochemical profile” increases the likelihood of identifying underlying processes on the molecular level, to detect disease-specific metabolic

signatures and to directly assess mechanisms of drug actions, eg, by measuring Inhibitors,research,lifescience,medical endogenous antioxidant levels to assess effects of antioxidant medications.93 The technical and methodological challenges of MRS at high magnetic fields and the strategies to overcome them in order to fully benefit from increased sensitivity and chemical shift dispersion at high fields have been recently reviewed.94 The quantification precision of MRS is improved at high fields,85,95-97 which is critical for preclinical and clinical applications. The most frequently only studied MRS biomarker N-acetylaspartate (NAA) is localized almost exclusively to neurons and is used as a surrogate for neuronal cell number and viability.98,99 Decreased NAA levels have been demonstrated in numerous neurological conditions and, therefore, are not very specific.80 Neurotransmitters glutamate and γ-aminobutyric acid (GABA), which offer potentially more specific information about neuronal status, have also been reliably quantified in vivo with high field MRS.