Robert M. Weisskoff

Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols

We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast‐enhanced T1‐weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd‐DTPA). These include a) the volume transfer constant Ktrans (min−1); b) the volume of extravascular extracellular space (EES) per unit volume of tissue ve (0 < ve < 1); and c) the flux rate constant between EES and plasma kep (min−1). The rate constant is the ratio of the transfer constant to the EES (kep = Ktrans/ve). Under flow‐limited conditions Ktrans equals the blood plasma flow per unit volume of tissue; under permeability‐limited conditions Ktrans equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards. J. Magn. Reson. Imaging 10:223–232, 1999.

Acute Effects of Cocaine on Human Brain Activity and Emotion

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.

Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo

Image distortion due to field gradient eddy currents can create image artifacts in diffusion‐weighted MR images. These images, acquired by measuring the attenuation of NMR signal due to directionally dependent diffusion, have recently been shown to be useful in the diagnosis and assessment of acute stroke and in mapping of tissue structure. This work presents an improvement on the spin‐echo (SE) diffusion sequence that displays less distortion and consequently improves image quality. Adding a second refocusing pulse provides better image quality with less distortion at no cost in scanning efficiency or effectiveness, and allows more flexible diffusion gradient timing. By adjusting the timing of the diffusion gradients, eddy currents with a single exponential decay constant can be nulled, and eddy currents with similar decay constants can be greatly reduced. This new sequence is demonstrated in phantom measurements and in diffusion anisotropy images of normal human brain. Magn Reson Med 49:177–182, 2003.

Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging.

Methods are presented to map complex fiber architectures in tissues by imaging the 3D spectra of tissue water diffusion with MR. First, theoretical considerations show why and under what conditions diffusion contrast is positive. Using this result, spin displacement spectra that are conventionally phase‐encoded can be accurately reconstructed by a Fourier transform of the measured signals modulus. Second, studies of in vitro and in vivo samples demonstrate correspondence between the orientational maxima of the diffusion spectrum and those of the fiber orientation density at each location. In specimens with complex muscular tissue, such as the tongue, diffusion spectrum images show characteristic local heterogeneities of fiber architectures, including angular dispersion and intersection. Cerebral diffusion spectra acquired in normal human subjects resolve known white matter tracts and tract intersections. Finally, the relation between the presented model‐free imaging technique and other available diffusion MRI schemes is discussed. Magn Reson Med, 2005.

Tracer arrival timing‐insensitive technique for estimating flow in MR perfusion‐weighted imaging using singular value decomposition with a block‐circulant deconvolution matrix

Relative cerebral blood flow (CBF) and tissue mean transit time (MTT) estimates from bolus‐tracking MR perfusion‐weighted imaging (PWI) have been shown to be sensitive to delay and dispersion when using singular value decomposition (SVD) with a single measured arterial input function. This study proposes a technique that is made time‐shift insensitive by the use of a block‐circulant matrix for deconvolution with (oSVD) and without (cSVD) minimization of oscillation of the derived residue function. The performances of these methods are compared with standard SVD (sSVD) in both numerical simulations and in clinically acquired data. An additional index of disturbed hemodynamics (oDelay) is proposed that represents the tracer arrival time difference between the AIF and tissue signal. Results show that PWI estimates from sSVD are weighted by tracer arrival time differences, while those from oSVD and cSVD are not. oSVD also provides estimates that are less sensitive to blood volume compared to cSVD. Using PWI data that can be routinely collected clinically, oSVD shows promise in providing tracer arrival timing‐insensitive flow estimates and hence a more specific indicator of ischemic injury. Shift maps can continue to provide a sensitive reflection of disturbed hemodynamics. Magn Reson Med 50:164–174, 2003.

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. Hum. Brain Mapping 7:89–97, 1999.

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.

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 α 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). Hum. Brain Mapping 6:239–249, 1998.

Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging

Background and Purpose— Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. Methods— Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. Results— At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P =0.02) but no significant improvement over algorithms utilizing PWI alone (P =0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P =0.02) or PWI (P =0.04). The performances of thresholding and GLM algorithms were comparable (P >0.2). Conclusions— Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.

MRI measurement of the temporal evolution of relative CMRO2 during rat forepaw stimulation

This study reports the first measurement of the relative cerebral metabolic rate of oxygen utilization (rCMRO2) during functional brain activation with sufficient temporal resolution to address the dynamics of blood oxygen level‐dependent (BOLD) MRI signal. During rat forepaw stimulation, rCMRO2 was determined in somatosensory cortex at 3‐sec intervals, using a model of BOLD signal and measurements of the change in BOLD transverse relaxation rate, the resting state BOLD transverse relaxation rate, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Average percentage changes from 10 to 30 sec after onset of forepaw stimulation for rCBF, rCBV, rCMRO2, and BOLD relaxation rate were 62 ± 16, 17 ± 2, 19 ± 17, and −26 ± 12, respectively. A poststimulus undershoot in BOLD signal was quantitatively attributed to the temporal mismatch between changes in blood flow and volume, and not to the role of oxygen metabolism. Magn Reson Med 42:944–951, 1999.