Nuclear magnetic resonance imaging and spectroscopy of human brain function

R. G. Shulman, A. M. Blamire, D. L. Rothman, G. McCarthy
1993 Proceedings of the National Academy of Sciences of the United States of America  
The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral vasculature has allowed measurements of regional cerebral blood volume (rCBV), which are activity dependent. Subsequent investigations linked the MR relaxation properties of brain
more » ... tissue to blood oxygenation levels which are also modulated by consumption and blood flow (rCBF). These methods have allowed mapping of brain activity in human visual and motor cortex as well as in areas of the frontal lobe involved in language. The methods have high enough spatial and temporal sensitivity to be used in individual subjects. MR spectroscopy of proton and carbon-13 nuclei has been used to measure rates of glucose transport and metabolism in the human brain. The steady-state measurements of brain glucose concentrations can be used to monitor the glycolytic flux, whereas subsequent glucose metabolismi.e., the flux into the cerebral glutamate pool-can be used to measure tricarboxylic acid cycle flux. Under visual stimulation the concentration of lactate in the visual cortex has been shown to increase by MR spectroscopy. This increase is compatible with an increase of anaerobic glycolysis under these conditions as earlier proposed from positron eniission tomography studies. It is shown how MR spectroscopy can extend this understanding of brain metabolism. During the last century it has become evident that sensory, motor, and cognitive functions can be mapped to discrete anatomical regions of the human brain. Early functional localization was often based upon changes in function following discrete brain lesions. These studies were extended by experiments in which electrical stimulation of discrete brain regions elicited movements, sensations, or complex cognitive functions such as language comprehension or memory. Powerful methods of modem biology have increasingly been concentrated on understanding brain function. Pioneering work of Kety and Schmidt (1) stimulated research on the coupling between brain electrical activity, metabolism, and cerebral blood flow. Recent radiolabel measurements, particularly positron emission tomography (PET) of spatially localized blood flow and metabolism, have provided new insights into the mapping ofbrain activity (2). The visual cortex has been the subject of particularly intense physiological, pharmacological, histological, and functional studies, although other sensory regions have been actively explored (3). Even complex cognitive functions of the frontal cortex are being identified and localized (4-6). In the past few years nuclear magnetic resonance (NMR) spectroscopy (MRS) and NMR imaging (MRI) have been used to map brain function. Both methods take advantage of the spin magnetic moment of certain nuclei, which usually have been 1H, 13C, or 31p. When placed in a static magnetic field (Bo), the nuclear magnetic moment results in the nuclear spin projections being quantized with respect to the magnetic field. The energy difference between parallel and antiparallel orientations in frequency units is proportional to the magnetic field by the Larmor relation v = (y/21r)Bo, where 'y is the gyromagnetic ratio characteristic of the particular nucleus. In the NMR experiment, transitions between spin orientations are induced by a radio frequency (RF) field at the Larmor frequency. The RF signal emitted by the NMR transition is measured by magnetic induction in a receiver coil. The Bo fields available for human brain experiments limit the Larmor frequency to the 20-to 200-MHz range. MRI measures the spatial distribution of magnetic nuclei by using magnetic "gradient" coils to produce a linear dependence of the Bo field on position, thereby establishing a direct connection between Larmor frequency and location. During acquisition of the MRI signal, the gradient coils are pulsed on three orthogonal axes to spatially encode the signal. After the signal is stored in a computer, a multidimensional Fourier transformation is applied to produce an image of the spatial distribution of the water signal. The image is divided into equal-size volume elements, which are called "vox-els." The difference in signal intensity between different voxels creates an image with contrast. Because of the high concentration of H20 in vivo (=40 M), the NMR signals are strong, so that modem MRI systems can resolve structures as small as 1 mm3 in humans. Imaging has been rapidly developed since 1973 (7), so that by 1977 images of H20 in the human body had been reported (8) and by 1983 commercial instruments were being installed in hospitals for clinical service. MRS in vivo builds upon well-established methods, which show that the same nucleus-i.e., 1H, 13C, or 31p-at different molecular sites will resonate at different frequencies in the same Bo field, thereby allowing resonances in the spectrum to be resolved and assigned to specific sites in different molecules. The first in vivo NMR spectra were obtained ofthe 31P nuclei in a suspension of erythrocytes (9). MRS studies of humans, which began with 31P NMR of limbs (10), have been extended to include 13C and 'H NMR observations (11) and are now routinely made on the human abdomen and brain. It is the purpose of this article to show how recent developments of MRS and MRI methods for studying the human brain are beginning to provide information about the spatial localization and metabolic changes associated with human brain activity. We sketch, at this early stage, the nature of these new NMR methods and indicate their accomplishments and promise as well as their present availability and limitations. MRI Studies of Brain Functional Activation Physical Dependencies of the MRI Signal. In MRI measurements of function-Abbreviations: NMR, nuclear magnetic resonance; MRS, magnetic resonance spectroscopy; MRI, magnetic resonance imaging; PET, positron emission tomography; rCBF, regional cerebral blood flow; rCBV, regional cerebral blood volume; rCMRglc, regional cerebral metabolic rate of glucose; rCMRO2, regional cerebral metabolic rate of oxygen; Ti, longitudinal (spin-lattice) relaxation time; T2, transverse (spin-spin) relaxation time; T , apparent T2; TE, echo time; vt,ca, tricarboxylic acid cycle rate; FLASH, fast low-angle shot method; EPI, echo-planar imaging. 3127
doi:10.1073/pnas.90.8.3127 pmid:8475050 pmcid:PMC46253 fatcat:77hageee2vftfkr5xnfdz5quoe