Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not.

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) estimates for high-grade gliomas computed with dynamic susceptibility contrast MR imaging are artificially lowered by contrast extravasation through a disrupted blood-brain barrier. We hypothesized that rCBV corrected for agent leakage would correlate significantly with histopathologic tumor grade, whereas uncorrected rCBV would not. METHODS: We performed dynamic T2*-weighted perfusion MR imaging on 43 patients with a cerebral glioma after prebolus gadolinium diethylene triamine penta-acetic acid administration to diminish competing extravasation-induced T1 effects. The rCBV was computed from non-necrotic enhancing tumor regions by integrating the relaxivity-time data, with and without contrast extravasation correction by using a linear fitting algorithm, and was normalized to contralateral brain. We determined the statistical correlation between corrected and uncorrected normalized rCBV and histopathologic tumor grade with the Spearman rank correlation test. RESULTS: Eleven, 9, and 23 patients had WHO grades II, III, and IV glioma, respectively. Mean uncorrected normalized rCBVs were 1.53, 2.51, and 2.14 (grade II, III, and IV). Corrected normalized rCBVs were 1.52, 2.84, and 3.96. Mean absolute discrepancies between uncorrected and corrected rCBVs were 2% (0%-15%), 16% (0%-106%), and 74% (0%-411%). The correlation between corrected rCBV and tumor grade was significant (0.60; P < .0001), whereas it was not for uncorrected rCBV (0.15; P = .35). CONCLUSION: For gliomas, rCBV estimation that correlates significantly with WHO tumor grade necessitates contrast extravasation correction. Without correction, artificially lowered rCBV may be construed erroneously to reflect lower tumor grade.

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.

Locally regularized spatiotemporal modeling and model comparison for functional MRI.

In this work we treat fMRI data analysis as a spatiotemporal system identification problem and address issues of model formulation, estimation, and model comparison. We present a new model that includes a physiologically based hemodynamic response and an empirically derived low-frequency noise model. We introduce an estimation method employing spatial regularization that improves the precision of spatially varying noise estimates. We call the algorithm locally regularized spatiotemporal (LRST) modeling. We develop a new model selection criterion and compare our model to the SPM-GLM method. Our findings suggest that our method offers a better approach to identifying appropriate statistical models for fMRI studies.

Magnetic resonance angiography at 0.3 T using MS-325.

Preliminary results on MS-325 versus ProHance enhanced magnetic resonance angiography (MRA) at low field strength in a rabbit model are reported. MS-325-enhanced images were acquired in vivo and compared with pre-contrast as well as conventional contrast-enhanced images. Visual image quality observations correlated with measurements of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). While published in vitro data show 7-fold greater relaxivity for MS-325 compared with conventional contrast agents, we observed an even greater effect here due, presumably, to better matching of the longer vascular lifetime with longer scan time in this study. In addition, overall vessel clarity improved significantly throughout all the phases of the experiment in MS-325-enhanced images when compared with conventional contrast-enhanced images.

A signal estimation approach to functional MRI.

In the last half decade, fast methods of magnetic resonance imaging have led to the possibility, for the first time, of non-invasive dynamic brain imaging. This has led to an explosion of work in the Neurosciences. From a signal processing viewpoint the problems are those of nonlinear spatio-temporal system identification. In this paper, we develop new methods of identification using novel spatial regularization. We also develop a new model comparison technique and use that to compare our method with existing techniques on some experimental data.

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.

Cardiac susceptibility artifacts arising from the heart-lung interface.

Cardiac MRI studies often show susceptibility artifacts along the inferoapical myocardial margin in both human and in vivo animal experiments at field strengths of 1.5T and greater. This study was designed to determine the cause of these artifacts in porcine myocardium at 3T. Gradient echo images were obtained under various anatomic and physiologic conditions to systematically study potential sources of local susceptibility gradients. Lung resection in the open-chested, euthanized swine was the only intervention that eliminated the artifact. The data suggest that in the porcine model, the heart-lung interface is the primary cause of these artifacts. Magn Reson Med 45:341-345, 2001.

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Myocardial fiber shortening in humans: initial results of MR imaging.

PURPOSE: To use diffusion-sensitive magnetic resonance (MR) imaging to obtain images of fiber orientation in vivo and to map fiber shortening in humans by means of integrating such data with strain images. MATERIALS AND METHODS: Images of fiber shortening for midventricular short-axis sections were acquired in eight healthy subjects. Fiber orientation maps obtained by means of diffusion-sensitive MR imaging were coregistered with systolic strain maps obtained by means of velocity-sensitive MR imaging. Fiber shortening was quantified by use of the component of systolic strain in the fiber direction. RESULTS: The results were reproducible among subjects and were consistent with published values. MR imaging of myocardial fibers showed axisymmetric progression of fiber angles from -90 degrees epicardially to +90 degrees endocardially, with maxima near 0 degrees. Fiber shortening (mean, 0.12 +/- 0.01 [SD]) was more uniform than radial, circumferential, longitudinal, or cross-fiber strain or any principal strain. Fiber orientation coincided with the direction of maximum contraction epicardially, with that of minimum contraction endocardially, and varied between these extremes linearly with wall depth (r = 0.6). CONCLUSION: Registered diffusion and strain MR imaging can be used quantitatively to map fiber orientation and its relations to myocardial deformation in humans.

Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke.

BACKGROUND AND PURPOSE: The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. METHODS: Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. RESULTS: In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. CONCLUSIONS: Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.

Cocaine activation discriminates dopaminergic projections by temporal response: an fMRI study in Rat.

We applied a sensitive new functional magnetic resonance imaging technique to identify the pattern and determinants of cocaine-induced brain activation in drug-naive rats. At doses greater than 0.1 mg/kg iv, cocaine produced robust activation throughout cortex with the largest magnitude increase in frontal neocortex. Additionally, we detected selective activation within dopamine-innervated subcortical regions including dorsomedial and ventrolateral striatum, nucleus accumbens region, and dorsal thalamus. Although dose response was similar among activated regions, temporal response differentiated regions along distinct anatomical boundaries with basal ganglia and limbic cortical structures, reaching maximum activation later than frontal neocortex. Pharmacological specificity was demonstrated by blocking cocaine-induced activation with SCH-23390, a selective D1 antagonist. Our data demonstrate the utility of fMRI to identify spatiotemporal patterns of cocaine-induced brain activation and implicate D1 dopaminergic mechanisms in acute cocaine action.

MRI measurement of the temporal evolution of relative CMRO(2) during rat forepaw stimulation.

This study reports the first measurement of the relative cerebral metabolic rate of oxygen utilization (rCMRO(2)) during functional brain activation with sufficient temporal resolution to address the dynamics of blood oxygen level-dependent (BOLD) MRI signal. During rat forepaw stimulation, rCMRO(2) 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, rCMRO(2), 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.

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 T(1)-weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd-DTPA). These include a) the volume transfer constant K(trans) (min(-1)); b) the volume of extravascular extracellular space (EES) per unit volume of tissue v(e) (0 < v(e) < 1); and c) the flux rate constant between EES and plasma k(ep) (min(-1)). The rate constant is the ratio of the transfer constant to the EES (k(ep) = K(trans)/v(e)). Under flow-limited conditions K(trans) equals the blood plasma flow per unit volume of tissue; under permeability-limited conditions K(trans) 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.

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.

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.

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.

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.

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.

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.