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The goal of improved spatial resolution in magnetic resonance imaging for better visualization of finer and finer structural details in the body is driven by a long tradition of microscopy in conventional anatomy. Centuries of anatomical studies have underscored the success with which the study of function and dysfunction can be complemented by the study of normal and pathological structure. Since relevant structures in the body span spatial scales from meters to the subcellular level, imaging technology has been pushed toward increasing resolution. Although there are solid motivations for imaging biological samples and small animal models with MR, a principal attraction of MR technology is the potential that advances in methodology can ultimately be adapted for use in living humans.

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.

As the race for increased magnetic field strength continues, ultra high field magnetic resonance systems are entering the clinical arena. Human brain imaging at ultra high field (7, 8, and 9.4 Tesla) offers an unprecedented resolution for anatomical imaging that approaches in-vivo microscopy. Results from healthy volunteers and from stroke and tumor studies have demonstrated that high field MRI can visualize microvasculature, details of pathological conditions, and iron deposits with a resolution not obtainable at lower fields. High-resolution maps of brain function and biochemical markers have been obtained at 7 Tesla. Clinical brain imaging is feasible at ultra high magnetic field, but more studies need to be done to determine its diagnostic potential.