In-Vivo NMR Spectroscopy of the Brain at High Fields

Abstract

Increased magnetic fields in principle provide increased sensitivity and specificity. In vivo, however, the increase in magnetic field alone does not automatically result in obvious improvements. Among the factors that are set to impede the improvements in sensitivity for in-vivo NMR spectroscopy are the increased challenges in eliminating the macroscopic inhomogeneities caused by mainly the air- tissue interface and increased RF power requirements. Changes in relaxation times may in addition adversely affect the increases in sensitivity, as T 1 tends to increase and T 2 tends to decrease with higher magnetic field. In the past 10 years at field strengths of 4 Tesla and higher, we have delineated technical advances that have permitted garnering the advantages of higher field, resulting in substantial gains for 1H and 13C NMR spectroscopy. The improvements can be broadly classified into increased sensitivity, leading to smaller volumes and shorter acquisition times and increased specificity, leading to the detection of many novel compounds. In dynamic 13C NMR it was shown that, in addition to measuring the label incorporation into several positions of many compounds, the time-resolved measurement of isotopomers was possible in the brain in vivo, leading to dynamic isotopomer analysis, a fusion of previously existing techniques. Improvements in sensitivity further advanced the use of localization in 13C NMR spectroscopy, which was critical in detection of brain glycogen metabolism in humans and rodents. Advances in 1H NMR spectroscopy permitted the precise measurement of an array of neurochemicals, ranging from Vitamin C, to glutathione, to glutamine, resulting in an extensive neurochemical profile of different extent that can be measured, e.g., in the unilateral mouse hippocampus, and human substantia nigra.