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Biomedical subjects

R M Weisskoff

Publications and source records attributed to R M Weisskoff.

At least 19 recordsLinked to original sources
PubMed1999

Language dominance determined by whole brain functional MRI in patients with brain lesions.

BACKGROUND: Functional MRI (fMRI) is of potential value in determining hemisphere dominance for language in epileptic patients. OBJECTIVE: To develop and validate an fMRI-based method of determining language dominance for patients with a wide range of potentially operable brain lesions in addition to epilepsy. METHODS: Initially, a within-subjects design was used with 19 healthy volunteers (11 strongly right-handed, 8 left-handed) to determine the relative lateralizing usefulness of three different language tasks in fMRI. An automated, hemispheric analysis of laterality was used to analyze whole brain fMRI data sets. To evaluate the clinical usefulness of this method, we compared fMRI-determined laterality with laterality determined by Wada testing or electrocortical stimulation mapping, or both, in 23 consecutive patients undergoing presurgical evaluation of language dominance. RESULTS: Only the verb generation task was reliably lateralizing. fMRI, using the verb generation task and an automated hemispheric analysis method, was concordant with invasive measures in 22 of 23 patients (12 Wada, 11 cortical stimulation). For the single patient who was discordant, in whom a tumor involved one-third of the left hemisphere, fMRI became concordant when the tumor and its reflection in the right hemisphere were excluded from laterality analysis. No significant negative correlation was obtained between lesion size and strength of laterality for the patients with lesions involving the dominant hemisphere. CONCLUSION: This fMRI method shows potential for evaluating language dominance in patients with a variety of brain lesions.

Adolescent↗
PubMed1999

Investigation of the early response to rat forepaw stimulation.

The role of relative cerebral blood volume (rCBV) in the early response of blood oxygenation level-dependent (BOLD) signal following sensory stimulation was assessed. Magnetic resonance imaging (MRI) measurements of rCBV and BOLD signal as a function of time (t) were compared with relative cerebral blood flow (rCBF) obtained by laser doppler flowmetry during a repeated epoch of rat forepaw stimulation in which 6 sec of electrical stimulation followed 54 sec of rest. rCBF(t) exceeded rCBV(t) in somatosensory cortex at all time points and reached a maximal increase (60%) during a 6 sec stimulation that was much higher than maximal rCBV (10%). An initial dip was not observed in BOLD signal, which showed a delay with respect to rCBF that was roughly consistent with the cerebral blood transit time.

Animals↗
PubMed1999

Measurement of human myocardial perfusion by double-gated flow alternating inversion recovery EPI.

This paper presents a flow-sensitive alternating inversion recovery (FAIR) method for measuring human myocardial perfusion at 1.5 T. Slice-selective/non-selective IR images were collected using a double-gated IR echoplanar imaging sequence. Myocardial perfusion was calculated after T1 fitting and extrapolation of the mean signal difference SI(Sel - SI(NSel). The accuracy of the method was tested in a porcine model using graded intravenous adenosine dose challenge. Comparison with radiolabeled microsphere measurements showed a good correlation (r = 0.84; mean error = 20%, n = 6) over the range of flows tested (0.9-7 ml/g/min). Applied in humans, this method allowed for the measurement of resting myocardial flow (1.04+/-0.37 ml/g/min, n = 11). The noise in our human measurements (SE(flow) = 0.2 ml/g/min) appears to come primarily from residual respiratory motion. Although the current signal-to-noise ratio limits our ability to measure small fluctuations in resting flow accurately, the results indicate that this noninvasive method has great promise for the quantitative assessment of myocardial flow reserve in humans.

Adult↗
PubMed1999

Echoplanar chemical shift imaging.

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.

Aspartic Acid↗
PubMed1999

Cardiac diffusion tensor MRI in vivo without strain correction.

Cardiac diffusion MRI with diffusion encoding that spans a cardiac cycle is complicated by myocardial strains. This paper presents a method to obtain accurate diffusion data without strain correction. Owing to the synchrony of normal cardiac motion, there are time points in the cardiac cycle, "sweet spots," when the cardiac configuration approximates its temporal mean. If the diffusion is encoded then, the net effect of strain on the observed diffusion approximates zero. To test this, MRI diffusion and strain-rate movies are performed on cyclically deformed gel phantoms and in five normal subjects. In phantoms, the sweet spots predicted from the strain time curves agree with the times when the observed diffusion equals the true diffusion. In humans, the strain prediction of the sweet spots and the locations determined by the diffusion trace show a high correlation, r = 0.99. In all subjects, diffusion MRI presents a fiber orientation pattern comparable to that obtained from a stationary specimen. Magn Reson Med 42:393-403, 1999.

Adult↗
PubMed1999

Evidence of a cerebrovascular postarteriole windkessel with delayed compliance.

A pronounced temporal mismatch was observed between the responses of relative cerebral blood volume (rCBV) measured by magnetic resonance imaging and relative cerebral blood flow measured by laser-Doppler flowmetry in rat somatosensory cortex after electrical forepaw stimulation. The increase of relative cerebral blood flow after stimulus onset and decrease after stimulus cessation were accurately described with a single exponential time constant of 2.4 +/- 0.8 seconds. In contrast, rCBV exhibited two distinct and nearly sequential processes after both onset and cessation of stimulation. A rapid change of rCBV (1.5 +/- 0.8 seconds) occurring immediately after onset and cessation was not statistically different from the time constant for relative cerebral blood flow. However, a slow phase of increase (onset) and decrease (cessation) with an exponential time constant of 14 +/- 13 seconds began approximately 8 seconds after the rapid phase of CBV change. A modified windkessel model was developed to describe the temporal evolution of rCBV as a rapid elastic response of capillaries and veins followed by slow venous relaxation of stress. Venous delayed compliance was suggested as the mechanism for the poststimulus undershoot in blood oxygen-sensitive magnetic resonance imaging signal that has been observed in this animal model and in human data.

Algorithms↗
PubMed1999

Modeling cerebral blood flow and flow heterogeneity from magnetic resonance residue data.

Existing model-free approaches to determine cerebral blood flow by external residue detection show a marked dependence of flow estimates on tracer arrival delays and dispersion. In theory, this dependence can be circumvented by applying a specific model of vascular transport and tissue flow heterogeneity. The authors present a method to determine flow heterogeneity by magnetic resonance residue detection of a plasma marker. Probability density functions of relative flows measured in six healthy volunteers were similar among tissue types and volunteers, and were in qualitative agreement with literature measurements of capillary red blood cell and plasma velocities. Combining the measured flow distribution with a model of vascular transport yielded excellent model fits to experimental residue data. Fitted gray-to-white flow-rate ratios were in good agreement with PET literature values, as well as a model-free singular value decomposition (SVD) method in the same subjects. The vascular model was found somewhat sensitive to data noise, but showed far less dependence on vascular delay and dispersion than the model-free SVD approach.

Adult↗
PubMed1999

Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time.

PURPOSE: To investigate additional information provided by maps of relative cerebral blood flow in functional magnetic resonance (MR) imaging of human hyperacute cerebral ischemic stroke. MATERIALS AND METHODS: Diffusion-weighted and hemodynamic MR imaging were performed in 23 patients less than 12 hours after the onset of symptoms. Maps of relative cerebral blood flow and tracer mean tissue transit time were computed, as were maps of apparent diffusion and relative cerebral blood volume. Acute lesion volumes on the maps were compared with follow-up imaging findings. RESULTS: In 15 of 23 subjects (65%), blood flow maps revealed hemodynamic abnormalities not visible on blood volume maps. A mismatch between initial blood flow and diffusion findings predicted growth of infarct more often (12 of 15 subjects with infarcts that grew) than did a mismatch between initial blood volume and diffusion findings (eight of 15). However, lesion volumes on blood volume and diffusion maps correlated better with eventual infarct volumes (r > 0.90) than did those on blood flow and tracer mean transit time maps (r approximately 0.6), likely as a result of threshold effects. In eight patients, blood volume was elevated around the diffusion abnormality, suggesting a compensatory hemodynamic response. CONCLUSION: MR imaging can delineate areas of altered blood flow, blood volume, and water mobility in hyperacute human stroke. Predictive models of tissue outcome may benefit by including computation of both relative cerebral blood flow and blood volume.

Acute Disease↗
PubMed1999

Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors.

OBJECT: In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema. METHODS: Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water. CONCLUSIONS: Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids.

Antineoplastic Agents, Hormonal↗
PubMed1999

Quantitative assessment of auditory cortex responses induced by imager acoustic noise.

A clustered volume acquisition functional MRI pulse sequence was modified to assess the response to the acoustic noise of echo-planar imaging in the auditory cortex and to determine whether it is possible to obtain data which is relatively free of acoustic contamination. The spatial location and strength (percent signal change) of cortical responses to the imager noise were examined by introducing extra gradient readouts, without slice excitation, to provide acoustic stimulation immediately prior to acquisition of a cerebral volume. The duration of acoustic stimulation was controlled by varying the number of extra gradient readouts. Slice acquisitions were clustered at the end of the repetition time (TR) period to prevent a response from being induced by the volume acquisition itself ("Intra-Acquisition Response"). The cerebral volumes were acquired using a long TR in order to limit the integration of the cortical response across volume acquisitions ("Inter-Acquisition Response"). Cortical responses were observed to be largest and most significant on the medial two-thirds of Heschl's gyrus, the location of primary auditory cortex. Mean signal changes induced by the imager noise were observed to be as high as 0.95%. A 2 sec delay prior to onset of the BOLD response was empirically determined. These results demonstrate that clustered volume acquisitions may be utilized for up to 2 sec of volume acquisition without inducing an appreciable Intra-Acquisition Response and can be used, with a sufficiently long TR, to provide data which are similarly free of any Inter-Acquisition Response.

Adult↗
PubMed1999

Improved auditory cortex imaging using clustered volume acquisitions.

The effects of the noise of echo-planar functional magnetic resonance imaging on auditory cortex responses were compared for two methods of acquiring functional MR data. Responses observed with a distributed volume acquisition sequence were compared to those obtained with a clustered volume acquisition sequence. In the former case, slices from the volume were acquired at equal intervals within the repetition time, whereas the latter acquired all slices in rapid succession at the end of the imaging period. The clustered volume acquisition provides a period of quiet during which a stimulus may be presented uninterrupted and uncontaminated by the noise of echo-planar imaging. Both sequences were implemented on a General Electric Signa imager retrofitted for echo-planar imaging by Advanced NMR Systems, Inc. The sequences were used to acquire 60 images per slice of a fixed volume of cerebral cortex while subjects were presented an instrumental music stimulus in an On vs. Off paradigm. Data were acquired for both sequences using TR values of 2, 3, 4, 6 and 8 sec. The clustered volume acquisition sequence was found to yield greater measures of dynamic range (percent signal change, mean statistical power per unit imaging time) across the tested range of TR values. Observations of more consistent spatial extent of responses, greater mean signal changes, and higher and more consistent values of mean t-statistic per unit imaging time demonstrate the efficacy of using a clustered volume acquisition for fMRI of auditory cortex.

Adult↗
PubMed1998

Calibrated functional MRI: mapping the dynamics of oxidative metabolism.

MRI was extended to the measurement of changes in oxidative metabolism in the normal human during functionally induced changes in cellular activity. A noninvasive MRI method that is model-independent calibrates the blood oxygen level dependent (BOLD) signal of functional MRI (fMRI) against perfusion-sensitive MRI, using carbon dioxide breathing as a physiological reference standard. This calibration procedure provides a regional measurement of the expected sensitivity of the fMRI BOLD signal to changes in the cellular activity of the brain. Maps of the BOLD signal calibration factor showed regional heterogeneity, indicating that the magnitude of functionally induced changes in the BOLD signal will be dependent on both the local change in blood flow and the local baseline physiology of the cerebral cortex. BOLD signal magnitude is shown to be reduced by 32% from its expected level by the action of oxygen metabolism. The calibrated fMRI technique was applied to stimulation of the human visual cortex with an alternating radial checkerboard pattern. With this stimulus oxygen consumption increased 16% whereas blood flow increased 45%. Although this result is consistent with previous findings of a significant difference between the increase in blood flow and oxygen consumption, it does indicate clearly that oxidative metabolism is a significant component of the metabolic response of the brain to functionally induced changes in cellular activity.

Brain↗
PubMed1998

Imaging subcortical auditory activity in humans.

There is a lack of physiological data pertaining to how listening humans process auditory information. Functional magnetic resonance imaging (fMRI) has provided some data for the auditory cortex in awake humans, but there is still a paucity of comparable data for subcortical auditory areas where the early stages of processing take place, as amply demonstrated by single-unit studies in animals. It is unclear why fMRI has been unsuccessful in imaging auditory brain-stem activity, but one problem may be cardiac-related, pulsatile brain-stem motion. To examine this, a method eliminating such motion (using cardiac gating) was applied to map sound-related activity in the auditory cortices and inferior colliculi in the brain stem. Activation in both the colliculi and cortex became more discernible when gating was used. In contrast with the cortex, the improvement in the colliculi resulted from a reduction in signal variability, rather than from an increase in percent signal change. This reduction is consistent with the hypothesis that motion or pulsatile flow is a major factor in brain-stem imaging. The way now seems clear to studying activity throughout the human auditory pathway in listening humans.

Auditory Cortex↗
PubMed1998

Perfusion-weighted imaging defects during spontaneous migrainous aura.

Perfusion- and diffusion-weighted magnetic resonance imaging was performed during spontaneous visual auras in four migraineurs. Alterations in relative cerebral blood flow (16-53% decrease), cerebral blood volume (6-33% decrease), and tissue mean transit time (10-54% increase) were observed in the gray matter of occipital cortex contralateral to the affected visual hemifield. No changes in the apparent diffusion coefficient were observed either while the patients were symptomatic or after resolution of the visual symptoms but before the onset of headache. Functional magnetic resonance imaging can be a useful noninvasive tool to study hemodynamic changes during spontaneous attacks of migraine with aura.

Adult↗
PubMed1998

Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation.

Dynamic measurements of regional changes in cerebral blood volume (CBV) were performed in rat models of hypercarbia and focal neuronal activation using T2-weighted imaging after injection of an intravascular contrast agent with a very long blood half-life. Calculated percent CBV change during hypercarbia was consistent with literature results from other non-invasive modalities. Equivalent percent CBV increases were found using spin- and gradient-echo images, suggesting proportional changes in blood volume for capillaries and small veins. During electrical stimulation of rat forepaw, focal CBV response to stimulation (24+/-4%) was significantly delayed relative to blood oxygen level dependent (BOLD) signal after both onset and cessation of stimulation. Poststimulus CBV decay was temporally consistent with the BOLD poststimulus undershoot. The use of exogenous agent increased the functional contrast-to-noise ratio relative to BOLD imaging by 5.7+/-1.3 at a magnetic field strength of 2 Tesla and 1.5+/-0.2 at 4.7 Tesla.

Animals↗
PubMed1998

Continuous assessment of perfusion by tagging including volume and water extraction (CAPTIVE): a steady-state contrast agent technique for measuring blood flow, relative blood volume fraction, and the water extraction fraction.

A new technique, CAPTIVE, that is a synthesis of arterial spin labeling (ASL) blood flow and steady-state susceptibility contrast relative blood volume imaging is described. Using a single injection of a novel, long half-life intravascular magnetopharmaceutical with a high tissue:blood susceptibility difference (deltachi) to deltaR1 ratio, changes in tissue transverse relaxivity (deltaR2 or deltaR2*) that arise from changes in blood volume were measured, while preserving the ability to measure blood flow using traditional T1-based ASL techniques. This modification permits the continuous measurement of both blood flow and blood volume. Also, because the contrast agent can be used to remove the signal from intravascular spins, it is possible to measure the first-pass water extraction fraction. Contrast-to-noise is easily traded off with repetition rate, allowing the use of non-EPI scanners and more flexible imaging paradigms. The basic theory of these measurements, several experimental scenarios, and validating results are presented. Specifically, the PaCO2-reactivity of microvascular and total relative cerebral blood volume (rCBV), cerebral blood flow (CBF), and the water extraction-flow product (EF) in rats with the new contrast agent MPEG-PL-DyDTPA is measured, and the values are concordant with those of previous literature. As an example of one possible application, continuous flow and volume measurements during transient focal ischemia are presented. It is believed that CAPTIVE imaging will yield a more complete picture of the hemodynamic state of an organ, and has further application for understanding the origins of the BOLD effect.

Animals↗
PubMed1998

NMR imaging of changes in vascular morphology due to tumor angiogenesis.

Tumor-sprouted vessels are greater in both number and diameter in comparison to their healthy counterparts. A novel technique based on magnetic susceptibility contrast mechanisms that are sensitive to varying sizes of blood vessels is presented to measure differences between the relaxation rates (1/T2 and 1/T2*) in a rat glioma model and normal cerebral cortex. deltaR2 and deltaR2*, the differences between relaxation rates precontrast and postcontrast agent injection, were measured for an intravascular equilibrium contrast agent (MION) at various echo times. Since deltaR2*/deltaR2 increases as vessel size increases, this ratio can be used as a measure of the average vessel size within an ROI or a voxel. The stability and longevity of the contrast agent within the vasculature were verified (n = 2 trials), and the ratio of deltaR2*/deltaR2 between the tumor and normal cortex was measured to be 1.9+/-0.2 (n = 4, echo time = 20 ms, and susceptibility difference (deltachi) approximately 10(-6)). This ratio compared favorably to a predicted ratio determined using histologically determined vessel sizes and theoretical Monte Carlo modeling results (1.9+/-0.1). Maps of the ratio of deltaR2*/deltaR2 were also made on a pixel-by-pixel basis. These techniques support the hypothesis that susceptibility contrast MRI can provide useful quantitative metrics of in vivo tumor vascular morphology.

Animals↗