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R M Weisskoff

Publications and source records attributed to R M Weisskoff.

At least 37 records · Page 2Linked to original sources
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

Human acute cerebral ischemia: detection of changes in water diffusion anisotropy by using MR imaging.

PURPOSE: To (a) determine the optimal choice of a scalar metric of anisotropy and (b) determine by means of magnetic resonance imaging if changes in diffusion anisotropy occurred in acute human ischemic stroke. MATERIALS AND METHODS: The full diffusion tensor over the entire brain was measured. To optimize the choice of a scalar anisotropy metric, the performances of scalar indices in simulated models and in a healthy volunteer were analyzed. The anisotropy, trace apparent diffusion coefficient (ADC), and eigenvalues of the diffusion tensor in lesions and contralateral normal brain were compared in 50 patients with stroke. RESULTS: Changes in anisotropy in patients were quantified by using fractional anisotropy because it provided the best performance in terms of contrast-to-noise ratio as a function of signal-to-noise ratio in simulations. The anisotropy of ischemic white matter decreased (P = .01). Changes in anisotropy in ischemic gray matter were not significant (P = .63). The trace ADC decreased for ischemic gray matter and white matter (P < .001). The first and second eigenvalues decreased in both ischemic gray and ischemic white matter (P < .001). The third eigenvalue decreased in ischemic gray (P = .001) and white matter (P = .03). CONCLUSION: Gray matter is mildly anisotropic in normal and early ischemic states. However, early white matter ischemia is associated with not only changes in trace ADC values but also significant changes in the anisotropy, or shape, of the water self-diffusion tensor.

Adult↗
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↗
PubMed1998

Imaging perfusion deficits in ischemic heart disease with susceptibility-enhanced T2-weighted MRI: preliminary human studies.

AIM: This feasibility study explores relative myocardial perfusion characterization with an investigational T2/T2 contrast agent. METHODS: Dysprosium-DTPA bis (methylamide) was administered peripherally in six patients with thallium defects. Rest and stress multi-section, gated, T2-weighted images were acquired with a 1.5 T echo-planar imager. Change in transverse relaxation rate was calculated in four segments for each subject. RESULTS: Magnetic resonance (MR) identified five of five instances of ischemia or infarction, at a dose of agent (0.25 mmol/kg) that was comparable to that currently used with clinically approved gadolinium agents. Injection at twice this dose resulted in saturation of the signal change, and the one ischemic segment corresponding to the higher dose was not identified by MR. MR was negative in two segments which, on final diagnosis, were determined to manifest thallium attenuation artifact. CONCLUSION: MR perfusion imaging with high susceptibility agents has the potential to characterize myocardial perfusion deficits.

Adult↗
PubMed1998

Mismatch between cerebral blood volume and flow index during transient focal ischemia studied with MRI and GD-BOPTA.

We investigated the regional and temporal changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and vascular transit time in seven mongrel cats during 30 min transient focal ischemia, caused by occlusion of the middle cerebral artery. Dynamic susceptibility contrast magnetic resonance imaging was done at 4.7 T, using fast gradient echo T2* weighted imaging and intravenous injection of gadolinium-BOPTA/Dimeglumine. During occlusion, the areas showing a blood volume change were predominantly within the middle cerebral artery territory and could be divided into areas showing either CBV increases or decreases. The area with decreased blood volume also had decreased blood flow as measured by our flow-based index (p < 0.05) and was located in the central territory of the middle cerebral artery. Peripheral to this region was an area showing increased blood volume but without significant CBF changes (p > 0.05). During reperfusion, the CBF increased in the entire zone showing changes in blood volume during occlusion, and remained significantly elevated until 45 min post-occlusion, while CBV remained elevated in the hyperemic rim for at least 2 h. The presence of a peri-ischemic zone showing flow/volume mismatch identified a region wherein baseline CBF is maintained by means of compensatory vasodilatation, but where the ratio of CBF to CBV is decreased. Dynamic susceptibility contrast magnetic resonance imaging with gadolinium-BOPTA/Dimeglumine may be a valuable technique for the investigation of regional and temporal perturbations of hemodynamics during ischemia and reperfusion.

Animals↗
PubMed1998

Determination of lingual myoarchitecture in whole tissue by NMR imaging of anisotropic water diffusion.

The muscular anatomy of the tongue consists of a complex three-dimensional array of fibers, which together produce the variations of shape and position necessary for deglutition. To define the myoarchitecture of the intact mammalian tongue, we have utilized NMR techniques to assess the location and orientation of muscle fiber bundles through measurement of the direction-specific diffusional properties of water molecules. Whole sheep tongues were excised and imaged with a slice-selective stimulated-echo diffusion sequence in the midline sagittal plane, and three-dimensional diffusion tensors were determined for each voxel. The derived diffusion tensors were depicted graphically as octahedra whose long axes indicate local muscle fiber orientation. Two distinct groups of midline fibers were identified: 1) in-plane sagittal fibers originating in the posteroinferior region of the tongue, radiating with a fanlike projection anteriorly and superiorly and merging with vertically oriented fibers, and 2) cross-plane (transverse) fibers, oriented at right angles to the vertically aligned fibers, predominantly in the anterior and superior regions of the tongue. Regional comparison of diffusion anisotropy revealed uniform and parallel alignment (high anisotropy) in the posteroinferior region of the tongue, corresponding to the base of the genioglossus, and less uniform, orthogonally aligned fibers (low anisotropy) in the anterosuperior region of the tongue, corresponding to the core intrinsic muscles. These data indicate that lingual myoarchitecture, determined through direction-dependent mobility of water molecules, can be depicted as discrete regions of muscle fibers, whose orientation and extent of diffusion anisotropy predict local contractility.

Animals↗
PubMed1998

Effect of temporal autocorrelation due to physiological noise and stimulus paradigm on voxel-level false-positive rates in fMRI.

Statistical mapping within a binary hypothesis testing framework is the most widely used analytical method in functional MRI of the brain. A common assumption in this kind of analysis is that the fMRI time series are independent and identically distributed in time, yet we know that fMRI data can have significant temporal correlation due to low-frequency physiological fluctuation (Weisskoff et al. [1993]; Proc Soc Magn Reson Med 9:7; Biswal et al. [1995]: Mag Reson Med 34:537-541). Furthermore, since the signal-to-noise ratio will vary with imaging rate, we should expect that the degree of correlation will vary with imaging rate. In this paper, we investigate the effect of temporal correlation and experimental paradigm on false-positive rates (type I error rates), using data synthesized through a simple autoregressive plus white-noise model whose parameters were estimated from real data over a range of imaging rates. We demonstrate that actual false-positive rates can be biased far above or below the assumed significance level alpha when temporal autocorrelation is ignored in a way that depends on both the degree of correlation as well as the paradigm frequency. Furthermore, we present a simple method, based on the noise model described above, for correcting such distortions, and relate this method to the extended general linear model of Worsley and Friston ([1995]: Neuroimage 2:173-181).

Acoustic Stimulation↗
PubMed1997

Dynamic liver imaging with iron oxide agents: effects of size and biodistribution on contrast.

In vivo effective relaxation rates in normal rat liver were evaluated for four dextran coated iron oxide agents: monocrystalline iron oxide nanocolloid (MION) with a mean particle diameter of 3.9 nm, a polycrystalline agent (PION) with a larger mean diameter of 12 nm, and these two agents labeled with the asialofetuin (ASF) protein for high hepatocytic receptor binding affinity (MION-ASF and PION-ASF). Using echo planar imaging at 2 Tesla, dose response was measured with measured with high temporal resolution for 3 h after injection of agent, and by comparing with relaxivities in vitro and in brain, dominant in vivo contrast phenomena were elucidated. While transverse relaxivity for PION-ASF exceeded that for MION-ASF by almost a factor of 2 in solution, relaxation rates in vivo became equivalent. Liver relaxation using non-ASF agents was consistent with rapid water exchange between vascular and extravascular compartments, which dominated relaxation as a result of agent accumulation in Kupffer cells.

Animals↗