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Background: The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation., Methods: Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images. Mean tumor rCBV normalized to white matter (nRCBV) and standardized rCBV (sRCBV) were determined for these regions of interest. The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan-Meier survival estimates with log-rank tests., Results: Patients surviving at least 1 year (OS-1) had significantly larger decreases in nRCBV at week 2 (P = .0451) and sRCBV at week 16 (P = .014). Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16, but not rCBV data at week 8, to be good prognostic markers for OS-1. Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 (P = .0015 and P = .0067 for nRCBV and P = .0251 and P = .0004 for sRCBV, respectively)., Conclusions: Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The anti-VEGF antibody, bevacizumab, is standard treatment for patients with recurrent glioblastoma. In this setting, traditional anatomic MRI methods such as post-contrast T1-weighted and T2-weighted imaging are proving unreliable for monitoring response. Here we evaluate the prognostic significance of pre- and posttreatment relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast MRI to predict response to bevacizumab., Methods: Thirty-six participants with recurrent high-grade gliomas who underwent rCBV imaging 60 days before and 20-60 days after starting bevacizumab treatment were enrolled. Tumor regions of interest (ROIs) were determined from deltaT1 maps computed from the difference between standardized post and precontrast T1-weighted images. Both pre- and posttreatment rCBV maps were corrected for leakage and standardized (stdRCBV) to a consistent intensity scale. The Kaplan-Meier method was used to determine if either the pre- or post-bevacizumab stdRCBV within the tumor ROI was predictive of overall survival (OS) or progression free survival (PFS)., Results: The OS was significantly longer if either the pre- (380d vs 175d; P=.0024) or posttreatment stdRCBV (340d vs 186d; P = .0065) was <4400. The posttreatment stdRCBV was also predictive of PFS (167d vs 78d; P = .0006). When the stdRCBV values were both above versus both below threshold, the OS was significantly worse (100.5d vs 395d; P < .0001). With a 32.5% decrease in stdRCBV, the risk of death was reduced by about 68% but increased by 140% with a 29% increase in stdRCBV., Conclusions: Standardized rCBV is predictive of OS and PFS in patients with recurrent high-grade brain tumor treated with bevacizumab., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The alpha diffusion-weighted imaging (DWI) method was developed to study heterogeneous water diffusion in the human brain using magnetic resonance imaging (MRI). An advantage of this model is that it does not require an assumption about the shape of the intravoxel distribution of apparent diffusion rates, and it has a calculable relationship to this distribution. The alpha-DWI technique is useful for detecting microstructural tissue changes associated with brain tumor invasion, and may be useful for directing therapy to invading tumor cells. In previous work, alpha-DWI was performed with magnetic field gradients applied along a single direction in order to avoid artificially introducing a source of heterogeneity to the decay. However, it is known that restricted diffusion is anisotropic in the brain, and the alpha-DWI method must take this into account to be complete. In this work the relationship between the applied magnetic field gradients and the fitted stretched-exponential model parameters was studied in the human brain. It was found the distributed diffusion coefficient (DDC) varies with the direction of applied gradients, while the heterogeneity index alpha is relatively direction-insensitive. It is proposed that in clinical use, maps of alpha can be created using diffusion-weighting gradients applied in a single direction that reflect the tissue heterogeneity.

Objective: To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively., Methods: We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P < 0.001) or t test (P < 0.001) analysis., Results: In 50 patients, a total of 85 functional areas were within 5 mm of the edge of a potentially resectable lesion. In 23 of these areas (27%), reduced fMRI signal in perilesional eloquent cortex in conjunction with preserved or increased signal in homologous contralateral brain areas revealed functional dominance opposite the side of the lesion. This suggested possible lesion-induced transhemispheric cortical reorganization to homologous brain regions (homotopic reorganization). In seven patients, however, the fMRI data were inconsistent with other methods of functional localization. In two patients with left inferior frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization., Conclusion: Lesion-induced neurovascular uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in conjunction with normal or increased activity in homologous brain regions, may simulate hemispheric dominance and lesion-induced homotopic cortical reorganization.

Experience with diffusion-weighted imaging (DWI) shows that signal attenuation is consistent with a multicompartmental theory of water diffusion in the brain. The source of this so-called nonexponential behavior is a topic of debate, because the cerebral cortex contains considerable microscopic heterogeneity and is therefore difficult to model. To account for this heterogeneity and understand its implications for current models of diffusion, a stretched-exponential function was developed to describe diffusion-related signal decay as a continuous distribution of sources decaying at different rates, with no assumptions made about the number of participating sources. DWI experiments were performed using a spin-echo diffusion-weighted pulse sequence with b-values of 500-6500 s/mm(2) in six rats. Signal attenuation curves were fit to a stretched-exponential function, and 20% of the voxels were better fit to the stretched-exponential model than to a biexponential model, even though the latter model had one more adjustable parameter. Based on the calculated intravoxel heterogeneity measure, the cerebral cortex contains considerable heterogeneity in diffusion. The use of a distributed diffusion coefficient (DDC) is suggested to measure mean intravoxel diffusion rates in the presence of such heterogeneity., (Copyright 2003 Wiley-Liss, Inc.)