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Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging--pilot study.

ABSTRACT: To derive a magnetic resonance (MR)-based imaging metric that reflects local perfusion changes resulting from the administration of angiogenic-inhibiting chemotherapy in patients with recurrent glioblastoma multiforme (GBM).In this retrospective Institutional Review Board-approved HIPAA-compliant study, 16 patients (12 men, four women; mean age, 51.8 years + or - 15.1 [standard deviation]) with recurrent GBM received bevacizumab every 3 weeks (15 mg per kilogram of body weight) as part of a clinical trial. Baseline MR images were acquired, and follow-up images were acquired every 6 weeks thereafter until tumor progression or death. Imaging included perfusion and T1-weighted contrast material-enhanced MR imaging. Perfusion images were analyzed both with and without correction for contrast material leakage. The volumes of interest were selected as enhancing voxels on T1-weighted contrast-enhanced MR images. Relative cerebral blood volume (rCBV) maps were created from analysis of MR perfusion images. The volumes of interest were used to calculate the following parameters: size, mean rCBV, mean leakage coefficient K(2), and hyperperfusion volume (HPV), which is the fraction of the tumor with an rCBV higher than a predetermined threshold. Percent change in each parameter from baseline to first follow-up was compared with time to progression (TTP) by using a Cox proportional hazards model with calculation of hazard ratios.The most significant hazard ratio was seen with a DeltaHPV cutoff of rCBV greater than 1.00 (hazard ratio, 1.077; 95% confidence interval: 1.026, 1.130; P = .002). The only significant ratios greater than one were those that resulted from perfusion calculated as mean rCBV and DeltaHPV. The ratios were also higher after correction for leakage.This pilot study derived an imaging metric (HPV) that reflects local perfusion changes in GBMs. This metric was found to show a significantly improved correlation to TTP as compared with more commonly used metrics.

SUBMITTER: Sawlani RN

PROVIDER: S-EPMC2858811 | biostudies-other | 2010 May

REPOSITORIES: biostudies-other

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Project description:PurposeTo determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images obtained in patients with normal bolus perfusion-weighted (PW) magnetic resonance (MR) imaging findings.Materials and methodsInstitutional review board approval and written informed patient consent were obtained. This study was HIPAA compliant. Consecutive patients suspected or known to have cerebrovascular disease underwent 1.5-T brain MR imaging, including MR angiography, gradient-echo PW imaging, and pseudocontinuous ASL imaging, between October 2007 and January 2008. Patients with normal bolus PW imaging findings were retrospectively identified, and two neuroradiologists subsequently evaluated the ASL images for focal abnormalities. The severity of the borderzone sign-that is, bilateral ASL signal dropout with surrounding cortical areas of hyperintensity in the middle cerebral artery borderzone regions-was classified by using a four-point scale. For each group, the ASL-measured mean mixed cortical cerebral blood flow (CBF) at the level of the centrum semiovale was evaluated by using the Jonckheere-Terpstra test.ResultsOne hundred thirty-nine patients met the study inclusion criteria, and 41 (30%) of them had normal bolus PW imaging findings. Twenty-three (56%) of these 41 patients also had normal ASL imaging findings. The remaining 18 (44%) patients had the ASL borderzone sign; these patients were older (mean age, 71 years +/- 11 [standard deviation] vs 57 years +/- 16; P < .005) and had lower mean CBF (30 mL/100 g/min +/- 12 vs 46 mL/100 g/min +/- 12, P < .003) compared with the patients who had normal ASL imaging findings. Five patients had additional focal ASL findings that were related to either slow blood flow in a vascular structure or postsurgical perfusion defects and were not visible on the PW images.ConclusionApproximately half of the patients with normal bolus PW imaging findings had abnormal ASL findings-most commonly the borderzone sign. Results of this pilot study suggest that ASL imaging in patients who have this sign and are suspected of having cerebrovascular disease yields additional and complementary hemodynamic information.

Project description:To evaluate the consistency of tumor blood volume measurements and antiangiogenic therapy efficacy assessments with a low-molecular-weight gadolinium-based contrast agent (GBCA, gadodiamide) versus an iron oxide nanoparticle (ferumoxytol) in the presence or absence of a loading dose of contrast agent before perfusion magnetic resonance (MR) imaging (preload method).The protocol was approved by the institutional animal care and use committee. U87MG tumor cells were implanted intracerebrally in 13 rats. All 13 rats underwent 11.75-T MR imaging with gadodiamide (60 μL) 13 days after tumor implantation. The next day, nine rats underwent MR imaging with ferumoxytol (60 μL). Immediately after ferumoxytol imaging, six rats received bevacizumab (45 mg/kg). MR imaging was repeated 48 hours after bevacizumab treatment with gadodiamide and 72 hours after treatment with ferumoxytol. Each study included three consecutive dynamic susceptibility-weighted contrast material-enhanced (DSC) MR acquisitions, which were performed without preload, with single-dose preload, and with double-dose preload. Tumor relative cerebral blood volume (rCBV) was estimated from each DSC MR acquisition. Two-way repeated measures analysis of variance was performed to test for differences between groups with both contrast agents.DSC MR imaging with gadodiamide and without preload showed low rCBV (≤ 1.75) in nine of the 13 tumors; estimated rCBV increased progressively with both single- and double-dose preloads (P < .001). Conversely, rCBVs obtained with ferumoxytol were high (>1.75) and remained constant with all three acquisitions. The magnitude of rCBV decrease after bevacizumab administration was dependent on the dose of gadodiamide preload, whereas the magnitude of rCBV decrease with ferumoxytol was constant regardless of whether contrast agent preload was used.With GBCA, tumor rCBV can be underestimated without preload and becomes dose dependent with preload correction. Conversely, ferumoxytol provides consistent assessment of tumor rCBV and antiangiogenic therapy efficacy.

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Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging--pilot study.

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