Kâmil Uğurbil

Multiband multislice GE-EPI at 7 tesla, with 16-fold acceleration using partial parallel imaging with application to high spatial and temporal whole-brain fMRI†

Parallel imaging in the form of multiband radiofrequency excitation, together with reduced k‐space coverage in the phase‐encode direction, was applied to human gradient echo functional MRI at 7 T for increased volumetric coverage and concurrent high spatial and temporal resolution. Echo planar imaging with simultaneous acquisition of four coronal slices separated by 44mm and simultaneous 4‐fold phase‐encoding undersampling, resulting in 16‐fold acceleration and up to 16‐fold maximal aliasing, was investigated. Task/stimulus‐induced signal changes and temporal signal behavior under basal conditions were comparable for multiband and standard single‐band excitation and longer pulse repetition times. Robust, whole‐brain functional mapping at 7 T, with 2 × 2 × 2mm3 (pulse repetition time 1.25 sec) and 1 × 1 × 2mm3 (pulse repetition time 1.5 sec) resolutions, covering fields of view of 256 × 256 × 176mm3 and 192 × 172 × 176mm3, respectively, was demonstrated with current gradient performance. Magn Reson Med 63:1144–1153, 2010.

High-field fMRI unveils orientation columns in humans

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90° (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.

Localized cerebral blood flow response at submillimeter columnar resolution

Functional magnetic resonance imaging (fMRI) has been widely used for imaging brain functions. However, the extent of the fMRI hemodynamic response around the active sites, at submillimeter resolution, remains poorly understood and controversial. With the use of perfusion-based fMRI, we evaluated the hemodynamic response in the cat visual cortex after orientation-specific stimuli. Activation maps obtained by using cerebral blood flow fMRI measurements were predominantly devoid of large draining vein contamination and reproducible at columnar resolution. Stimulus-specific cerebral blood flow responses were spatially localized to individual cortical columns, and columnar layouts were resolved. The periodic spacing of orientation columnar structures was estimated to be 1.1 ± 0.2 mm (n = 14 orientations, five animals), consistent with previous findings. The estimated cerebral blood flow response at full width at half-maximum was 470 μm under single-stimulus conditions without differential subtraction. These results suggest that hemodynamic-based fMRI can indeed be used to map individual functional columns if large-vessel contributions can be minimized or eliminated.

Sustained Neuronal Activation Raises Oxidative Metabolism to a New Steady-State Level: Evidence from 1H NMR Spectroscopy in the Human Visual Cortex

To date, functional 1H NMR spectroscopy has been utilized to report the time courses of few metabolites, primarily lactate. Benefiting from the sensitivity offered by ultra-high magnetic field (7 T), the concentrations of 17 metabolites were measured in the human visual cortex during two paradigms of visual stimulation lasting 5.3 and 10.6 mins. Significant concentration changes of approximately 0.2 μmol/g were observed for several metabolites: lactate increased by 23% ± 5% (P < 0.0005), glutamate increased by 3% ± 1% (P < 0.01), whereas aspartate decreased by 15% ± 6% (P < 0.05). Glucose concentration also manifested a tendency to decrease during activation periods. The lactate concentration reached the new steady-state level within the first minute of activation and came back to baseline only after the stimulus ended. The changes of the concentration of metabolites implied a rise in oxidative metabolism to a new steady-state level during activation and indicated that amino-acid homeostasis is affected by physiological stimulation, likely because of an increased flux through the malate—aspartate shuttle.

LOCALIZED IN VIVO 13C-NMR OF GLUTAMATE METABOLISM IN THE HUMAN BRAIN : INITIAL RESULTS AT 4 TESLA

Using optimized administration of 13C-labeled glucose, the time course of the specific activity of glucose was measured directly by in vivo 13C-NMR in the human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3 and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly observed for the first time in vivo, suggesting a substantial GABA turnover in the normal human visual cortex. Likewise, lactate C3 labeled with an estimated active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism is proposed which predicts that glutamatergic action (‘neurotransmission’), pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange across the mitochondrial membrane can be assessed simultaneously in the human brain.

Steady-state cerebral glucose concentrations and transport in the human brain

Abstract: Understanding the mechanism of brain glucose transport across the blood‐brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport have been generally described using standard Michaelis‐Menten kinetics. These models predict that the steady‐state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis‐Menten constant for half‐maximal transport, Kt. In experiments where steady‐state plasma glucose content was varied from 4 to 30 mM, the brain glucose level was a linear function of plasma glucose concentration. At plasma concentrations nearing 30 mM, the brain glucose level approached 9 mM, which was significantly higher than predicted from the previously reported Kt of ∼4 mM (p < 0.05). The high brain glucose concentration measured in the human brain suggests that ablumenal brain glucose may compete with lumenal glucose for transport. We developed a model based on a reversible Michaelis‐Menten kinetic formulation of unidirectional transport rates. Fitting this model to brain glucose level as a function of plasma glucose level gave a substantially lower Kt of 0.6 ± 2.0 mM, which was consistent with the previously reported millimolar Km of GLUT‐1 in erythrocyte model systems. Previously reported and reanalyzed quantification provided consistent kinetic parameters. We conclude that cerebral glucose transport is most consistently described when using reversible Michaelis‐Menten kinetics.

Spatiotemporal dynamics of the BOLD fMRI signals: Toward mapping submillimeter cortical columns using the early negative response

The existence of the early‐negative blood‐oxygenation‐level‐dependent (BOLD) response is controversial and its practical utility for mapping brain functions with columnar spatial specificity remains questionable. To address these issues, gradient‐echo BOLD fMRI studies were performed at 4.7 T and 9.4 T using the well‐established orientation column model in the cat visual cortex. A robust transient early‐negative BOLD response was consistently observed in anesthetized cat (‐0.35 ± 0.09%, mean ± SD, n = 8 at 2.9 ± 0.5 sec poststimulus onset for 4.7 T, TE = 31 ms; ‐0.29 ± 0.10%, n = 4 at 3.0 ± 0.8 sec poststimulus onset for 9.4 T, TE = 12 ms). In addition to its temporal evolution, the BOLD response also evolved dynamically in the spatial domain. The initially spatially localized early‐negative signal appeared to dynamically drain from the active sites toward large vessels, followed by a wave of the delayed positive signal, which exhibited similar spatiotemporal dynamics. Only the early‐negative BOLD response within 2 sec of the stimulus onset (not the entire dip) yielded columnar layouts without differential subtraction. The functional maps of two orthogonal orientations using the first 2‐sec dip were indeed complementary. On the other hand, the delayed positive BOLD response appeared diffused and extended beyond the active sites. It was thus less suitable to resolve columnar layouts. These results have implications for the design and interpretation of the BOLD fMRI at columnar resolution. Magn Reson Med 44:231–242, 2000.

How accurate is magnetic resonance imaging of brain function

Since it was introduced a decade ago, functional magnetic resonance imaging (fMRI) has come to dominate research on the human brain. However, fMRI maps are based on secondary metabolic and hemodynamic events that follow neuronal activity, and not on the electrical activity itself. Therefore, the representation provided by fMRI cannot be assumed a priori to be exact. The accuracy of these maps depends on the spatial extent of the metabolic and hemodynamic changes induced by neuronal activity, and the role played by the vasculature in converting these changes to signals detected by magnetic resonance imaging. Significant progress has been made in both areas, suggesting that it is possible to obtain both spatially accurate and quantitative data on brain function from magnetic resonance methodologies.

Ultra High-Resolution fMRI in Monkeys with Implanted RF Coils

Spatiotemporally resolved functional MRI (fMRI) in animals can reveal how wide-spread neural networks are organized and accompanying electrophysiological recordings can show how small neural assemblies contribute to this organization. Here we present a novel technique that yields high-resolution structural and functional images of the monkey brain with small, tissue-compatible, intraosteally implantable radiofrequency coils. Voxel sizes as small as 0.0113 microl with high signal-to-noise and contrast-to-noise ratios were obtained, revealing both structural and functional cortical architecture in great detail. Up to a certain point, contrast sensitivity increased with decreasing voxel size, probably because of the decreased partial volume effects. Spatial specificity was demonstrated by the lamina-specific activation in experiments comparing responses to moving and flickering stimuli. The implications of this technique for combined fMRI/electrophysiology experiments and its limitations in terms of spatial coverage are discussed.

A geometrically adjustable 16-channel transmit/receive transmission line array for improved RF efficiency and parallel imaging performance at 7 Tesla.

A novel geometrically adjustable transceiver array system is presented. A key feature of the geometrically adjustable array was the introduction of decoupling capacitors that allow for automatic change in capacitance dependent on neighboring resonant element distance. The 16‐element head array version of such an adjustable coil based on transmission line technology was compared to fixed geometry transmission line arrays (TLAs) of various sizes at 7T. The focus of this comparison was on parallel imaging performance, RF transmit efficiency, and signal‐to‐noise ratio (SNR). Significant gains in parallel imaging performance and SNR were observed for the new coil and attributed to its adjustability and to the design of the individual elements with a three‐sided ground plane. Magn Reson Med, 2008.