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Biomedical subjects

R M Weisskoff

Publications and source records attributed to R M Weisskoff.

At least 55 records · Page 3Linked to original sources

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.

Adult↗

Dynamic echo-planar imaging of the breast: experience in diagnosing breast carcinoma and correlation with tumor angiogenesis.

PURPOSE: To correlate quantitative echo-planar magnetic resonance (MR) imaging measures of gadopentetate dimeglumine tumor uptake with histologic diagnoses and microvessel density (MVD) and to compare dynamic echo-planar imaging of breast lesions with conventional dynamic MR imaging techniques. MATERIALS AND METHODS: The study group comprised 63 patients (aged 13-70 years) with 71 breast lesions who underwent conventional and echo-planar MR imaging. The T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with the echo-planar imaging data and were correlated with histologic findings and MVD estimates. Extraction-flow product data normalized to pectoral muscle gadopentetate dimeglumine concentration in invasive cancers was also correlated with MVD. RESULTS: On average, cancer T1 values were shorter than benign values, but there was substantial overlap between the two groups. Cancers had higher extraction-flow products than benign lesions (P < .001). Sensitivity, specificity, positive predictive value, and negative predictive value were 83%, 79%, 67%, and 90%, respectively. Receiver operating characteristic analysis showed improved performance with extraction-flow products than with percentages of signal intensity change. Among the invasive cancers, there was no significant correlation between extraction-flow product and MVD. CONCLUSION: The T1 value remains important in more precise quantitative estimation of gadopentetate dimeglumine uptake in breast tumors, which helps improve the specificity of dynamic imaging. Tumor MVD affects the contrast medium enhancement of breast lesions, but other factors contribute.

Breast↗

Characterization of cerebral blood oxygenation and flow changes during prolonged brain activation.

The behavior of cerebral blood flow and oxygenation during prolonged brain activation was studied using magnetic resonance imaging (MRI) sensitized to flow and oxygenation changes, as well as positron emission tomography sensitized to flow. Neuronal habituation effects and hemodynamic changes were evaluated across tasks and cortical regions. Nine types of activation stimuli or tasks, including motor activation, vibrotactile stimulation, and several types of visual stimulation, were used. Both flow and oxygenation were evaluated in separate time course series as well as simultaneously using two different MRI methods. In most cases, the activation-induced increase in flow and oxygenation remained elevated for the entire stimulation duration. These results suggest that both flow rate and oxygenation consumption rate remain constant during the entire time that primary cortical neurons are activated by a task or a stimulus.

Blood Flow Velocity↗

Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.

BACKGROUND: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.

Adult↗

Perfusion changes in human skeletal muscle during reactive hyperemia measured by echo-planar imaging.

Muscle performance is markedly influenced by tissue perfusion. Techniques that allow quantification of microvascular flow are limited by the use of ionizing radiation. In this investigation, we apply an NMR model previously developed by Detre et al. to the measurement of human muscle perfusion during reactive hyperemia. We compare our results with conventional plethysmography adapted to NMR. Using echo-planar imaging, T1 and T2 were measured in 14 subjects during rest, ischemia, and reactive hyperemia. Mean leg muscle T1 in healthy volunteers is 850 ms at rest and 834 ms at reperfusion, leading to a calculated reactive hyperemia flow increase (T1 flow) of 103 +/- 40 ml/100 ml/min. T1 flows correlate well with NMR-plethysmography values. Changes in T2, which are sensitive to both deoxyhemoglobin content and vessel diameter variations, are also correlated with perfusion measurements. T1 changes allow quantification of regional perfusion in human muscle during reactive hyperemia.

Adult↗

Continuous assessment of relative cerebral blood volume in transient ischemia using steady state susceptibility-contrast MRI.

The utility of a noninvasive steady state susceptibility-contrast MRI technique for continuous measurement of relative cerebral blood volume (rCBV) during global transient ischemia and subsequent hyperemia in a feline ischemia model is demonstrated. The measurements were obtained during a 10-min period of occlusion and 1-h period of reperfusion. Maximal hyperemic responses in gray matter, basal ganglia, and white matter (observed at 7,7, and 5 min, respectively) were 1.9 +/- 0.5, 1.8 +/- 0.3, and 1.7 +/- 0.6 times greater than baseline CBV (mean +/- SEM). Thirty to forty minutes after onset of reperfusion, CBV returned to normal. Thereafter, it decreased below baseline, nearing the control level by 1 h after onset of reperfusion. Steady state susceptibility-contrast MRI permits continuous, in vivo mapping of alterations in CBV.

Animals↗

Myocardial intensity changes associated with flow stimulation in blood oxygenation sensitive magnetic resonance imaging.

Functional magnetic resonance imaging exploits deoxygenated blood as an endogenous source for contrast in assessing local changes in tissue perfusion. Intrinsic changes in myocardial signal intensity were measured during dipyridamole induced coronary vasodilatation with T2*-weighted echo planar MRI in healthy volunteers. Concurrently, changes in flow velocity in the left anterior descending coronary artery were measured using a time-of-flight method. Dipyridamole infusion produced 14 +/- 6% increase in myocardial signal intensity (n = 7). Temporal profile of the myocardial signal intensity changes correlated well with the augmentation of coronary flow velocity. The data are consistent with the concept that changes in myocardial deoxyhemoglobin content due to altered flow result in changes in magnetic susceptibility that can be detected on T2*-weighted MR images.

Adult↗

Simple measurement of scanner stability for functional NMR imaging of activation in the brain.

Functional MR imaging (fMRI) of activation in the brain is one of the more demanding applications required of an NMR imaging instrument. Since the signal changes in activation imaging are quite small, any instrumental variations can easily compromise the fMRI contrast. The authors describe a simple method for measuring these scanner instabilities, which is implementable on all scanners, to determine whether instability is degrading the fMRI contrast-to-noise. In this method, a long time series of images is acquired with identical imaging parameters to the chosen fMRI scans, the fluctuations are measured as a function of region-of-interest (ROI) size, and compared with the single image SNR. By plotting these fluctuations versus ROI size, and comparing them with the theoretically approachable value, the impact of these fluctuations can be assessed. We also present a simplified version of the test, which can be implemented with minimal calculations.

Brain↗

High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis.

The authors review the theoretical basis of determination of cerebral blood flow (CBF) using dynamic measurements of nondiffusible contrast agents, and demonstrate how parametric and nonparametric deconvolution techniques can be modified for the special requirements of CBF determination using dynamic MRI. Using Monte Carlo modeling, the use of simple, analytical residue models is shown to introduce large errors in flow estimates when actual, underlying vascular characteristics are not sufficiently described by the chosen function. The determination of the shape of the residue function on a regional basis is shown to be possible only at high signal-to-noise ratio. Comparison of several nonparametric deconvolution techniques showed that a nonparametric deconvolution technique (singular value decomposition) allows estimation of flow relatively independent of underlying vascular structure and volume even at low signal-to-noise ratio associated with pixel-by-pixel deconvolution.

Cerebrovascular Circulation↗

High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part II: Experimental comparison and preliminary results.

This report evaluates several methods to map relative cerebral blood flow (rCBF) by applying both parametric and nonparametric techniques to deconvolve high resolution dynamic MRI measurements of paramagnetic bolus passages with noninvasively determined arterial inputs. We found a nonparametric (singular value decomposition (SVD)) deconvolution technique produced the most robust results, giving mean gray:white flow ratio of 2.7 +/- 0.5 (SEM) in six normal volunteers, in excellent agreement with recent PET literature values for age-matched subjects. Similar results were obtained by using a model-dependent approach that assumes an exponential residue function, but not for a Gaussian-shaped residue function or for either Fourier or regularization-based model-independent approaches. Pilot studies of our CBF mapping techniques in patients with tumor, stroke, and migraine aura demonstrated that these techniques can be readily used on data routinely acquired by using current echo planar imaging technology. By using these techniques, the authors visualized important regional hemodynamic changes not detectable with rCBV mapping algorithms.

Adult↗

Improving MR quantification of regional blood volume with intravascular T1 contrast agents: accuracy, precision, and water exchange.

The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T1 contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T1 and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a "no-exchange" model provide the best trade-off between accuracy and precision.

Adenocarcinoma↗

Echo-planar magnetic resonance imaging of deglutitive vocal fold closure: normal and pathologic patterns of displacement.

Abnormalities of vocal fold closure during deglutition predispose to aspiration due to impairment of airway protection. Conventional assessment of deglutitive vocal fold motion with laryngoscopy does not permit visualization through a complete adduction-abduction cycle. We determined spatiotemporal patterns of deglutitive vocal fold adduction through echo-planar magnetic resonance imaging in 15 normal volunteers and 6 patients with vocal fold paralysis. In normal volunteers, deglutitive vocal fold adduction was synchronized with laryngeal elevation, with complete vocal fold closure at the apex. Patients with unilateral vocal fold paralysis demonstrated reduced elevation and medial movement of the involved vocal fold. At maximal laryngeal elevation the uninvolved vocal fold attained a position superior to the paralyzed fold, resulting in level differences and an interglottic gap. Patients with bilateral vocal fold paralysis demonstrated reduced elevation and medial movement of both vocal folds. These findings indicate that normal and abnormal patterns of vocal fold displacement can be distinguished noninvasively through the use of echo-planar imaging.

Adult↗

Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging.

PURPOSE: To evaluate acute stroke with conventional, multisection diffusion-weighted (DW), and hemodynamically weighted (HW) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The three MR imaging techniques were performed in 11 patients within 10 hours of the onset of acute hemiparesis. The volume of DW and HW abnormalities were compared with infarct volumes depicted at initial and/or follow-up MR or computed tomography (CT). RESULTS: Findings at DW and HW imaging were abnormal in nine of the 11 patients, despite normal findings at initial CT and/or MR. In all nine patients, infarcts were depicted at follow-up CT or MR. The DW abnormality was generally smaller and the HW abnormality was generally larger than the infarct volume determined at subsequent imaging. In the two patients with normal findings at DW and HW imaging, symptoms resolved completely within 1-48 hours. CONCLUSION: Different aspects of hyperacute cerebral ischemia are depicted at DW and HW imaging before infarction is depicted at conventional MR or CT. These techniques may improve stroke diagnosis and may contribute to advances in treatment.

Acute Disease↗

Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle.

Using nuclear magnetic resonance (NMR), we have examined the relationship of high-energy phosphate metabolism and perfusion in human soleus and gastrocnemius muscles. With 31P-NMR spectroscopy, we monitored phosphocreatine (PCr) decay and recovery in eight normal volunteers and four heart failure patients performing ischemic plantar flexion. By using echo-planar imaging, perfusion was independently measured by a local [inversion-recovery (T1-flow)] and a regional technique (NMR-plethysmography). After correction for its pH dependence, PCr recovery time constant is 27.5 +/- 8.0 s in normal volunteers, with mean flow 118 +/- 75 (soleus and gastrocnemius T1-flow) and 30.2 +/- 9.7 ml.100 ml-1.min-1 (NMR-plethysmography-flow). We demonstrate a positive correlation between PCr time constant and local perfusion given by y = 50 - 0.15x (r2 = 0.68, P = 0.01) for the 8 normal subjects, and y = 64 - 0.24x (r2 = 0.83, P = 0.0001) for the 12 subjects recruited in the study. Regional perfusion techniques also show a significant but weaker correlation. Using this totally noninvasive method, we conclude that aerobic ATP resynthesis is related to the magnitude of perfusion, i.e., O2 availability, and demonstrate that magnetic resonance imaging and magnetic resonance spectroscopy together can accurately assess muscle functional status.

Adult↗

Echo-planar MR determination of relative cerebral blood volume in human brain tumors: T1 versus T2 weighting.

PURPOSE: Maps related to relative cerebral blood volume (rCBV) were generated with the use of the T1 effects produced by a low-dose bolus passage of gadopentetate dimeglumine. The T1 maps were evaluated in a tumor population and compared with rCBV maps obtained with T2-weighted measurements. METHODS: Imaging was performed in 19 patients with suspected intraaxial brain tumors. For the T1 rCBV maps, a low-dose bolus of contrast material was given during T1-weighted interleaved spin-echo echo-planar MR imaging. This was followed by a second injection during serial T2-weighted imaging for generation of the T2 rCBV maps. RESULTS: Among patients with low-grade lesions (n = 9), T1-based and T2-based rCBV maps showed comparably low rCBV in 7 subjects. In the other 2 patients, with confirmed tumor dedifferentiation, elevation of rCBV values was seen on maps obtained with both techniques. Among patients with high-grade tumors (n = 10), 4 had no evidence of recurrence and 6 did have tumor recurrence (confirmed by follow-up and positron emission tomography). In patients with the high-grade lesions exhibiting conventional contrast enhancement, lesions tended to have higher estimated values on T1 rCBV maps than on the T2 rCBV maps. CONCLUSION: Although the T1 rCBV maps showed less contrast as compared with the T2 rCBV maps, they provided diagnostic information that was comparable to the T2 rCBV maps in our series of 19 patients with primary brain tumors.

Adult↗

Motionless movies of myocardial strain-rates using stimulated echoes.

We present methods to acquire and analyze NMR movies of myocardial strain rates in which cardiac motion is suppressed and the histories of strain rates are accurately defined for each voxel of myocardial tissue. By means of stimulated echoes, the myocardial strain-rate tensor is phase-encoded at progressive delays in the cardiac cycle while the slice-select and spatial encoding of the image acquisition are performed at a constant cardiac delay. In these data, every image shows the identical myocardial tissue, and the anatomic configuration of the heart appears motionless. The myocardial strain-rate data, however, indicate the state of motion which existed in this slice at the time of the velocity phase-encoding, and these data evolve with the progressive delay as a movie. Using echo-planar MRI, motionless movies of myocardial strain rate of four to eight cardiac delays are obtained in a breath-hold. As an application, a quantitative characterization of cardiac mechanical synchrony is accomplished by principal component analysis (PCA) of the time series of strain rates.

Algorithms↗

The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo.

Understanding the relationship between fMRI signal changes and activated cortex is paramount to successful mapping of neuronal activity. To this end, the relative extravascular and intravascular contribution to fMRI signal change from capillaries (localized), venules (less localized) and macrovessels (remote, draining veins) must be determined. In this work, the authors assessed both the extravascular and intravascular contribution to blood oxygenation level-dependent gradient echo signal change at 1.5 T by using a Monte Carlo model for susceptibility-based contrast in conjunction with a physiological model for neuronal activation-induced changes in oxygenation and vascular volume fraction. The authors compared our Model results with experimental fMRI signal changes with and without velocity sensitization via bipolar gradients to null the intravascular signal. The model and experimental results are in agreement and suggest that the intravascular spins account for the majority of fMRI signal change on T2*-weighted images at 1.5 T.

Blood Flow Velocity↗

Dynamic Gd-DTPA enhanced MRI measurement of tissue cell volume fraction.

A new technique for measuring tissue cellular volume fraction, based on an improved modeling of the dynamic distribution of Gd-DTPA and the effect of proton exchange, is described. This technique uses peak T1 enhancement and blood Gd-DTPA concentration to compute tissue cellular volume fraction. The feasibility of this technique is demonstrated with computer simulations that explore the limits of the simplifying assumptions (small vascular space, slow vascular-extravascular proton exchange), and by direct comparison of MR and radionuclide cell fraction measurements made in muscle, liver, and tumor tissue in a rat model. The computer simulations demonstrate that with slow to intermediate vascular proton exchange and vascular fractions less than 10% the error in our cell fraction measurements typically remains less than 10%. Consistent with this prediction, a direct comparison between MR and radionuclide measurements of cell fraction demonstrates mean percent differences of less than 10%:1.9% in muscle (n = 4); 9% in liver (n = 1) and 9.5% in tumor (n = 4). Similarly, for all rats studied, the MR-measured cell fractions (muscle (0.92 +/- 0.04, n = 20); liver (0.76 +/- 0.11, n = 9); whole tumor (0.69 +/- 0.15, n = 22)) agree with the cell fraction values reported in the literature. In general, the authors' results demonstrate the feasibility of a simple method for measuring tissue cell fraction that is robust across a broad range of vascular volume, flow, and exchange conditions. Consequently, this method may prove to be an important means for evaluating the response of tumors to therapy.

Animals↗