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Biomedical subjects

K Ugurbil

Publications and source records attributed to K Ugurbil.

At least 19 recordsLinked to original sources

Retinotopic mapping of lateral geniculate nucleus in humans using functional magnetic resonance imaging.

Subcortical nuclei in the thalamus, which play an important role in many functions of the human brain, provide challenging targets for functional mapping with neuroimaging techniques because of their small sizes and deep locations. In this study, we explore the capability of high-resolution functional magnetic resonance imaging at 4 Tesla for mapping the retinotopic organization in the lateral geniculate nucleus (LGN). Our results show that the hemifield visual stimulation only activates LGN in the contralateral hemisphere, and the lower-field and upper-field visual stimulations activate the superior and inferior portion of LGN, respectively. These results reveal a similar retinotopic organization between the human and nonhuman primate LGN and between LGN and the primary visual cortex. We conclude that high-resolution functional magnetic resonance imaging is capable of functional mapping of suborganizations in small nuclei together with cortical activation. This will have an impact for studying the thalamocortical networks in the human brain.

Adult

Myocardial oxygenation during high work states in hearts with postinfarction remodeling.

BACKGROUND: Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. METHODS AND RESULTS: Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31P NMR and deoxymyoglobin (Mb-delta) with 1H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 microg x kg-1 x min-1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-delta. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-delta. CONCLUSIONS: Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.

Adenosine Triphosphate

Human primary visual cortex and lateral geniculate nucleus activation during visual imagery.

The functional magnetic resonance (fMRI) technique can be robustly used to map functional activation of the visual pathway including the primary visual cortex (V1), the lateral geniculate nucleus (LGN), and other nuclei of humans during visual perception stimulation. One of the major controversies in visual neuroscience is whether lower-order visual areas involve the visual imagery process. This issue was examined using fMRI at high magnetic field. It was demonstrated for the first time that the LGN was activated during visual imagery process in the human brain together with V1 and other activation. There was a tight coupling of the activation between V1 and the LGN during visual imagery.

Adult

Imaging of H217O distribution in the brain of a live rat by using proton-detected 17O MRI.

Imaging of H217O has a number of important applications. Mapping the distribution of H217O produced by oxidative metabolism of 17O-enriched oxygen gas may lead to a new method of metabolic functional imaging; regional cerebral blood flow also can be measured by measuring the H217O distribution after the injection of 17O-enriched physiological saline solution. Previous studies have proposed a method for indirect detection of 17O. The method is based on the shortening of the proton T2 in H217O solutions, caused by the residual 17O-1H scalar coupling and transferred to the bulk water via fast chemical exchange. It has been shown that the proton T2 of H217O solutions can be restored to that of H216O by irradiating the resonance frequency of the 17O nucleus. The indirect 17O image thus is obtained by taking the difference between two T2-weighted spin-echo images: one acquired after irradiation of the 17O resonance and one acquired without irradiation. It also has been established that, at relatively low concentrations of H217O, the indirect method yields an image that quantitatively reflects the H217O distribution in the sample. The method is referred to as PRIMO (proton imaging of oxygen). In this work, we show in vivo proton images of the H217O distribution in a rat brain after an i.v. injection of H217O-enriched physiological saline solution. Implementing the indirect detection method in an echo-planar imaging sequence enabled obtaining H217O images with good spatial and temporal resolution of few seconds.

Animals

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

Animals

Human hippocampal long-term sustained response during word memory processing.

Temporal behavior of activation associated with the neural substrate of human memory function was investigated during and after an auditorily instructed word memory task using multislice functional magnetic resonance imaging. The hippocampal formation, which is involved in human memory function, displayed a long-term sustained response that persisted significantly (approximately 90 s) beyond the duration of the memory task. This sustained period was approximately two-fold longer than the duration of the post-task activation observed in auditory areas and Broca's area, which are involved in the phonological loop of the verbal working memory. These observations suggest that the hippocampal memory processing involves sustained activation in the transitional function for the long-term memory over the working memory period.

Adult

Mapping of lateral geniculate nucleus activation during visual stimulation in human brain using fMRI.

Functional magnetic resonance imaging has been successfully used to map the activation in the lateral geniculate nucleus (LGN) in both hemispheres as well as the primary visual cortex (V1) during a checkerboard visual stimulation. The average blood oxygenation level dependent (BOLD) change in LGN was less than that in V1. However, the BOLD temporal responses were similar between LGN and V1. The activation in the pulvinar nucleus during visual perception was also detected, and its activated location could be separated from LGN in 3D images. The LGN activation between intersubject and intrasubject multiple trials was compared. The results demonstrate that fMRI can reliably and robustly detect small subcortical nucleus activation in the human brain.

Adult

Spatial and temporal differentiation of fMRI BOLD response in primary visual cortex of human brain during sustained visual simulation.

The blood oxygenation level dependent (BOLD) response during sustained visual stimulation has been studied by several groups using fMRI with controversial conclusions. This issue was investigated for the human brain at high (4 Tesla) magnetic field strength using a flashing goggle at 8 Hz. The results demonstrate that the overall BOLD response in the primary visual cortex has an initial overshoot after the onset of visual stimulation and an undershoot after the termination of visual stimulation. A significant and positive BOLD response, however, remains constant between the initial and terminal transient responses. The temporal BOLD responses in the primary visual cortex were spatially dependent. The regions identified as draining veins in images displayed proportionately larger initial and terminal transient responses, whereas regions devoid of such vessels and associated mainly with parenchyma exhibited a more time-independent BOLD response. These results reveal that the BOLD effect and, presumably, the uncoupling between cerebral blood flow and cerebral metabolic rate of oxygen consumption, are maintained in the primary visual cortex during sustained visual stimulation, and the temporal characteristics of the BOLD effect are spatially dependent.

Humans

Detecting natural abundance carbon signal of NAA metabolite within 12-cm3 localized volume of human brain using 1H-[13C] NMR spectroscopy.

NMR spectroscopy has been applied extensively to study metabolism noninvasively in the human brain and other tissues. However, it usually suffers from poor signal-to-noise ratio due to low NMR sensitivity and low metabolite concentrations. In this study, the technique of proton-observe-carbon-edited (POCE) NMR spectroscopy combined with a single-shot localization sequence was used to detect the natural abundance carbon signal of the amino acid N-acetyl aspartate from a 12-cm3 localized volume in the occipital lobe of humans at 4 T. The results suggest that NMR spectroscopy is sensitive enough to detect signals from low concentration metabolites (< 60 nmol/g) from small volumes in the human brain within several minutes of data acquisition. This reveals that in vivo NMR spectroscopy is a promising technique for detecting small metabolite changes and low traces of 13C isotopic labeling for dynamic metabolism studies aimed at investigating physiological and pathological questions.

Aspartic Acid

Activation of visuomotor systems during visually guided movements: a functional MRI study.

The dorsal stream is a dominant visuomotor pathway that connects the striate and extrastriate cortices to posterior parietal areas. In turn, the posterior parietal areas send projections to the frontal primary motor and premotor areas. This cortical pathway is hypothesized to be involved in the transformation of a visual input into the appropriate motor output. In this study we used functional magnetic resonance imaging (fMRI) of the entire brain to determine the patterns of activation that occurred while subjects performed a visually guided motor task. In nine human subjects, fMRI data were acquired on a 4-T whole-body MR system equipped with a head gradient coil and a birdcage RF coil using a T2*-weighted EPI sequence. Functional activation was determined for three different tasks: (1) a visuomotor task consisting of moving a cursor on a screen with a joystick in relation to various targets, (2) a hand movement task consisting of moving the joystick without visual input, and (3) a eye movement task consisting of moving the eyes alone without visual input. Blood oxygenation level-dependent (BOLD) contrast-based activation maps of each subject were generated using period cross-correlation statistics. Subsequently, each subject's brain was normalized to Talairach coordinates, and the individual maps were compared on a pixel by pixel basis. Significantly activated pixels common to at least four out of six subjects were retained to construct the final functional image. The pattern of activation during visually guided movements was consistent with the flow of information from striate and extrastriate visual areas, to the posterior parietal complex, and then to frontal motor areas. The extensive activation of this network and the reproducibility among subjects is consistent with a role for the dorsal stream in transforming visual information into motor behavior. Also extensively activated were the medial and lateral cerebellar structures, implicating the cortico-pontocerebellar pathway in visually guided movements. Thalamic activation, particularly of the pulvinar, suggests that this nucleus is an important subcortical target of the dorsal stream.

Animals

Functional magnetic resonance imaging of motor, sensory, and posterior parietal cortical areas during performance of sequential typing movements.

We investigated the activation of sensory and motor areas involved in the production of typing movements using functional magnetic resonance imaging (fMRI). Eleven experienced typists performed tasks, in which the spatial and temporal requirements as well as the number of digits involved were varied. These included a simple uni-digit repetitive task, a uni-digit sequential task, a dual-digit sequential task, a multi-digit sequential task, and typing text from memory. We found that the production of simple repetitive keypresses with the index finger primarily involved the activation of contralateral primary motor cortex (M1), although a small activation of the supplementary motor area (SMA) and other regions was sometimes observed as well. The sequencing of keypresses involved bilateral M1 and a stronger activation of the SMA and to a lesser extent the premotor area, cingulate gyrus, caudate, and lentiform nuclei. However, the activation of these areas did not exclusively depend on the complexity of the movements, since they were often activated during more simple movements, such as alternating two keypresses repeatedly. Somatosensory and parietal regions were also found to be activated during typing sequences. The activation of parietal areas did not exclusively depend on the spatial requirements of the task, since similar activation was observed during movements within intra-personal space (finger-thumb opposition) and may instead be related to the temporal requirements of the task. Our findings suggest that the assembly of well-learned, goal-directed finger movement sequences involves the SMA and other secondary motor areas as well as somatosensory and parietal areas.

Adult

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

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 approximately 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.

Adult

On the characteristics of functional magnetic resonance imaging of the brain.

In this review we discuss various recent topics that characterize functional magnetic resonance imaging (fMRI). These topics include a brief description of MRI image acquisition, how to cope with noise or signal fluctuation, the basis of fMRI signal changes, and the relation of MRI signal to neuronal events. Several observations of fMRI that show good correlation to the neurofunction are referred to. Temporal characteristics of fMRI signals and examples of how the feature of real time measurement is utilized are then described. The question of spatial resolution of fMRI, which must be dictated by the vascular structure serving the functional system, is discussed based on various fMRI observations. Finally, the advantage of fMRI mapping is shown in a few examples. Reviewing the vast number of recent fMRI application that have now been reported is beyond the scope of this article.

Animals

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.

Aspartic Acid

Time-resolved fMRI of mental rotation.

Time-resolved fMRI seeks to elucidate neuronal activity during a single execution of a mental task, which corresponds typically to a timescale of seconds. However, this is also the timescale of the hemodynamic response, which delays and blurs the signal in time. In order to distinguish the temporal characteristics of the neuronal activity from that of the hemodynamic response, which is often vaguely known, we recorded a set of fMRI time courses under conditions of a varying behavioral parameter, and correlated this parameter to the width of the fMRI response. For the task under investigation, the mental rotation of three-dimensional objects, we found that the activation in the parietal lobe is related to an aspect of the task that is described by the reaction time (for example, the very act of mental rotation), and not only to aspects of the task that are constant from trial to trial, such as the visual presentation at the beginning or the decision at the end of the task.

Brain Mapping

Relationships between myocardial bioenergetic and left ventricular function in hearts with volume-overload hypertrophy.

BACKGROUND: Left ventricular (LV) hypertrophy secondary to volume overload can result in alterations in myocardial bioenergetics and LV dysfunction. This study examined whether bioenergetic abnormalities contribute to the pump dysfunction. METHODS AND RESULTS: Severe mitral regurgitation (MR) was produced in 10 dogs by disruption of the chordal apparatus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocardial high-energy phosphates were measured by using magnetic resonance spectroscopy at rest, during coronary vasodilation with adenosine, and during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the hemodynamic and LV function were normal at rest, but abnormalities developed during beta-blockade and exercise. Myocardial creatine phosphate-to-ATP ratios were significantly lower in each layer across the LV wall in MR hearts than normal hearts. Myocardial blood flow and coronary reserve were normal in MR hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobutamine infusion well. CONCLUSIONS: In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.

Adenosine Triphosphate

Functional magnetic resonance imaging of the human brain.

The current technical and methodological status of functional magnetic resonance imaging (fMRI) is reviewed. The mechanisms underlying the effects of deoxyhemoglobin concentration and cerebral blood flow changes are discussed, and methods for monitoring these changes are described and compared. Methods for post-processing fMRI data are outlined. Potential problems and solutions related to vessels and motion are discussed in detail.

Brain