PubMed Health⌕ Search

Biomedical subjects

Kâmil Uğurbil

Publications and source records attributed to Kâmil Uğurbil.

14 recordsLinked to original sources
PubMed2006

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 micromol/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.

Adult↗
PubMed2006

Sensitivity of single-voxel 1H-MRS in investigating the metabolism of the activated human visual cortex at 7 T.

Proton magnetic resonance spectroscopy (1H-MRS) has been used in a number of studies to noninvasively assess the temporal changes of lactate in the activated human brain. However, the results have not been consistent. The aim of the present study was to test the sensitivity of 1H-MRS during functional experiments at the highest magnetic field currently available for human studies (7 T). Stability and reproducibility of the measurements were evaluated from LCModel analysis of time series of spectra measured during a visual stimulation paradigm and by examination of the difference between spectra obtained at rest and during activation. The sensitivity threshold to detect concentration changes was 0.2 micromol/g for most of the quantified metabolites. The possible variations of metabolite concentrations during visual stimulation were within the same range (+/-0.2 micromol/g). In addition, the influence of a small line-narrowing effect due to the blood oxygenation level-dependent (BOLD) T2* changes on the estimated concentrations was simulated. Quantification of metabolites was, in general, not affected beyond 1% by line-width changes within 0.5 Hz.

Humans↗
PubMed2006

In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective.

In vivo 13C NMR spectroscopy has the unique capability to measure metabolic fluxes noninvasively in the brain. Quantitative measurements of metabolic fluxes require analysis of the 13C labeling time courses obtained experimentally with a metabolic model. The present work reviews the ingredients necessary for a dynamic metabolic modeling study, with particular emphasis on practical issues.

Animals↗
PubMed2006

Frontiers of brain mapping using MRI.

Over the past dozen years, the use of MRI techniques to map brain function (fMRI) has sparked a great deal of research. The ability of fMRI to image several different physiological processes concurrently (i.e., blood oxygenation, blood flow, metabolism) and noninvasively over large volumes make it the ideal choice for many different areas of neuroscience research in addition to countless applications in clinical settings. Furthermore, with the advent of high magnetic fields (and other hardware advancements, i.e., parallel imaging) for both human and animal research, spatial and temporal resolutions continue to be pushed to higher levels because of increases in the sensitivity as well as specificity of MR-detectable functional signals. fMRI methodology continues to grow and has the ability to cater to many different research applications. There seems to be no foreseeable end in sight to the advancement of fMRI techniques and its subsequent use in basic research as well as in clinical settings. In this work, fMRI techniques and the ongoing development of existing techniques are discussed with implications for the future of fMRI.

Brain Mapping↗
PubMed2006

Investigating brain metabolism at high fields using localized 13C NMR spectroscopy without 1H decoupling.

Most in vivo 13C NMR spectroscopy studies in the brain have been performed using 1H decoupling during acquisition. Decoupling imposes significant constraints on the experimental setup (particularly for human studies at high magnetic field) in order to stay within safety limits for power deposition. We show here that incorporation of the 13C label from 13C-labeled glucose into brain amino acids can be monitored accurately using localized 13C NMR spectroscopy without the application of 1H decoupling. Using LCModel quantification with prior knowledge of one-bond and multiple-bond J(CH) coupling constants, the uncertainty on metabolites concentrations was only 35% to 91% higher (depending on the carbon resonance of interest) in undecoupled spectra compared to decoupled spectra in the rat brain at 9.4 Tesla. Although less sensitive, 13C NMR without decoupling dramatically reduces experimental constraints on coil setup and pulse sequence design required to keep power deposition within safety guidelines. This opens the prospect of safely measuring 13C NMR spectra in humans at varied brain locations (not only the occipital lobe) and at very high magnetic fields above 4 Tesla.

Animals↗
PubMed2005

Logarithmic transformation for high-field BOLD fMRI data.

Parametric statistical analyses of BOLD fMRI data often assume that the data are normally distributed, the variance is independent of the mean, and the effects are additive. We evaluated the fulfilment of these conditions on BOLD fMRI data acquired at 4 T from the whole brain while 15 subjects fixated a spot, looked at a geometrical shape, and copied it using a joystick. We performed a detailed analysis of the data to assess (a) their frequency distribution (i.e. how close it was to a normal distribution), (b) the dependence of the standard deviation (SD) on the mean, and (c) the dependence of the response on the preceding baseline. The data showed a strong departure from normality (being skewed to the right and hyperkurtotic), a strong linear dependence of the SD on the mean, and a proportional response over the baseline. These results suggest the need for a logarithmic transformation. Indeed, the log transformation reduced the skewness and kurtosis of the distribution, stabilized the variance, and made the effect additive, i.e. independent of the baseline. We conclude that high-field BOLD fMRI data need to be log-transformed before parametric statistical analyses are applied.

Adult↗
PubMed2005

Mental maze solving: directional fMRI tuning and population coding in the superior parietal lobule.

The superior parietal lobule (SPL) of six human subjects was imaged at 4 T during mental traversing of a directed maze path. Here we demonstrate the orderly involvement of the SPL in this function, as follows. Forty-two percent of the voxels were tuned with respect to the direction of the maze path. This suggests a coherent tuning of local neuronal populations contributing to the change of the single-voxel BOLD signal. Preferred directions ranged throughout the directional continuum of 360 degrees. Voxels with similar preferred directions tended to cluster together: on average there were seven same-direction clusters per slice, with an average cluster membership of five voxels/cluster and an average nearest-neighbor same-direction intercluster distance of 13.1 mm. On the other hand, the average nearest-neighbor intercluster distance between a given direction and all other directions was 3.1 mm. This suggests a patchy arrangement such that patches of directionally tuned voxels, containing voxels with different preferred directions, alternate with patches of non-tuned voxels. Finally, the population vector predicted accurately the direction of the maze path (with an error of 12.7 degrees), and provided good estimates (with an error of 29 degrees) when calculated within parts of the SPL. Altogether, these findings document a new, orderly functional organization of the SPL with respect to mental tracing.

Adult↗
PubMed2005

Signal and noise characteristics of Hahn SE and GE BOLD fMRI at 7 T in humans.

At very high magnetic fields, GE BOLD fMRI is expected to contain nonspecific contributions and behave differently than HSE fMRI data. Similarly, the two approaches can conceivably suffer from different contributions to temporal instabilities in a times series that ultimately determine the contrast-to-noise ratio (CNR). We investigate the signal and signal fluctuation characteristics in GE and HSE fMRI data with the imaging parameters separately optimized for each contrast at 7 T. In HSE fMRI, activation-induced fractional signal change (DeltaS/S) decreased rapidly, and the ratio of standard deviations of image-to-image fluctuations due to physiological processes (sigmaPhys) to thermal noise (sigmaTherm) remained constant with increasing voxel volume. In contrast, DeltaS/S as well as volume of activated voxels was virtually independent of voxel size for GE BOLD, and sigma(Phys)/sigmaTherm increased with increasing voxel size. The ratio of BOLD signal changes (GE/HSE) was much closer to 1 in tissue areas compared to vessel areas. These observations led to the conclusions that the spatial extent of the activation-induced DeltaS/S was much broader in the GE data, and that the physiological processes that give rise to the temporal fluctuations lost coherence over millimeter distances in HSE compared to GE fMRI data. While further studies are needed to characterize it fully, sigmaPhys in HSE data was clearly different than in GE data. It was concluded that HSE imaging yields a significantly reduced amount of nonspecific signals compared to GE imaging, and, would be the method of choice (over GE) for high-resolution applications in humans.

Adult↗
PubMed2005

Uncovering hidden in vivo resonances using editing based on localized TOCSY.

A novel single-shot spectral editing technique for in vivo proton NMR is proposed to recover resonances of low-concentration metabolites obscured by very strong resonances. With this new method, editing is performed by transferring transverse magnetization to J-coupled spins from selected coupling partners using a homonuclear Hartmann-Hahn polarization transfer with adiabatic pulses. The current implementation uses 1D-TOCSY with single-voxel localization based on LASER to recover the H1 proton of beta-glucose at 4.63 ppm from under water and the lactate methyl resonances from beneath a strong lipid signal. The method can be extended to further spin systems where conventional editing methods are difficult to perform.

Animals↗
PubMed2005

Exchange-influenced T2rho contrast in human brain images measured with adiabatic radio frequency pulses.

Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T(2rho,ex) and T(2rho,dd)) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T(2rho) contrast in images of the human occipital lobe at magnetic field of 4 T. T(2rho) time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude-and frequency-modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T(2rho) time constants. Measurements of the apparent relaxation time constants (T(2) (dagger)) of brain tissue water as a function of the time between centers of pulses (tau(cp)) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T(2rho) relaxation influenced by DA in tissue and provide a means to generate T(2rho) contrast in MRI.

Brain Mapping↗
PubMed2003

Spin-echo fMRI in humans using high spatial resolutions and high magnetic fields.

The Hahn spin-echo (HSE)-based BOLD effect at high magnetic fields is expected to provide functional images that originate exclusively from the microvasculature. The blood contribution that dominates HSE BOLD contrast at low magnetic fields (e.g., 1.5 T), and degrades specificity, is highly attenuated at high fields because the apparent T(2) of venous blood in an HSE experiment decreases quadratically with increasing magnetic field. In contrast, the HSE BOLD contrast is believed to arise from the microvasculature and increase supralinearly with the magnetic field strength. In this work we report the results of detailed and quantitative evaluations of HSE BOLD signal changes for functional imaging in the human visual cortex at 4 and 7 T. This study used high spatial resolution, afforded by the increased signal-to-noise ratio (SNR) of higher field strengths and surface coils, to avoid partial volume effects (PVEs), and demonstrated increased contrast-to-noise ratio (CNR) and spatial specificity at the higher field strengths. The HSE BOLD signal changes induced by visual stimulation were predominantly linearly dependent on the echo time (TE). They increased in magnitude almost quadratically in going from 4 to 7 T when the blood contribution was suppressed using Stejskal-Tanner gradients that suppress signals from the blood due to its inhomogeneous flow and higher diffusion constant relative to tissue. The HSE signal changes at 7 T were modeled accurately using a vascular volume of 1.5%, in agreement with the capillary volume of gray matter. Furthermore, high-resolution acquisitions indicate that CNR increased with voxel sizes < 1 mm(3) due to diminishing white matter or cerebrospinal fluid-space vs. gray matter PVEs. It was concluded that the high-field HSE functional MRI (fMRI) signals originated largely from the capillaries, and that the magnitude of the signal changes associated with brain function reached sufficiently high levels at 7 T to make it a useful approach for mapping on the millimeter to submillimeter spatial scale.

Adult↗
PubMed2003

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.

Brain↗
PubMed2003

Cerebellar activation during copying geometrical shapes.

We studied functional MRI activation in the cerebellum during copying 9 geometrical shapes (equilateral triangle, isosceles triangle, square, diamond, vertical trapezoid, pentagon, hexagon, circle, and vertical lemniscate). Twenty subjects were imaged during 3 consecutive 45-s periods (rest, visual presentation, and copying). First, there was a positive relation between cerebellar activation and the peak speed of individual movements. This effect was strongest in the lateral and posterior ipsilateral cerebellum but it was also present in the paramedian zones of both cerebellar hemispheres and in the vermis. A finer grain analysis of the relations between the time course of the blood oxygenation level-dependent activation and movement parameters revealed a significant relation to hand position and speed but not to acceleration. Second, there was a significant relation between the intensity of voxel activation during visual presentation and the speed of the upcoming movement. The spatial distribution of these voxels was very similar to that of the voxels activated during copying, indicating that the cerebellum might be involved in motor rehearsal, in addition to its role during movement execution. Finally, a factor analysis of the intensity of activated voxels in the ipsilateral cerebellum during copying (adjusted for the speed effect) extracted 3 shape factors. Factor 1 reflected "roundness," factor 2 "upward pointing," and factor 3 "pointing (up or down) and elongation." These results link cerebellar activation to more global, spatial aspects of copying.

Adult↗