Improved Perfusion MR Imaging Assessment of Intracerebral Tumor Blood Volume and Antiangiogenic Therapy Efficacy in a Rat Model with Ferumoxytol

Abstract

Purpose:To evaluate the consistency of tumor blood volume measurements and antiangiogenic therapy effi cacy 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). Materials and Methods: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 m L) 13 days after tumor implantation. The next day, nine rats underwent MR imaging with ferumoxytol (60 m L). 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. Results:DSC MR imaging with gadodiamide and without preload showed low rCBV ( Յ 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. Conclusion: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 effi cacy.q RSNA, 2011

Pseudoprogression of Glioblastoma after Chemo- and Radiation Therapy: Diagnosis by Using Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging with Ferumoxytol versus Gadoteridol and Correlation with Survival

“…Leakage correction works best with limited extravasation rates, above which the blood space and extravascular extracellular space becomes intrinsically indistinguishable when GBCA is used, and the derived rCBV value and leakage rate are no longer independent. The results of our preclinical rodent study also showed that brain tumor rCBV was underestimated when GBCA was used in a human high-grade glioma xenograft, and the accuracy of the measurement was improved by using the preload leakage correction method; however, rCBV values depended on the dose of contrast agent preload (37). By using ferumoxytol for DSC MR imaging in the same animals, we obtained consistent and rCBV underestimation, which can potentially lead to incorrect diagnosis, treatment, and prognosis and necessity of leakage correction.…”

“…Paulson et al (35) found variability in tumor rCBV depending on the choice of five different mathematic correction algorithms. Moreover, our preclinical study (37) results showed the inconsistency of preload methods for leakage correction. The most commonly used of these two methods required either sophisticated postprocessing or high contrast-agent dose exposure but was still inconsistent.…”

Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL

“…Based on our prior work, immediate post-USPIO MRI shows intravascular, not abnormal parenchymal enhancement. [22][23][24] The second day of imaging at 24 hours is a relatively intracellular-weighted (and/or interstitial-weighted) rather than intravascular-weighted MRI given that ferumoxytol has an intravascular halflife of approximately 14 to 20 hours. 25 This proved helpful in one patient in this series who underwent a second diagnostic biopsy in which a different surgical target was selected based on the T2-weighted USPIOenhanced MRI.…”

Pseudoprogression after glioma therapy: a comprehensive review

“…Can characterize tissues and pathologic processes at the microscopic level ADC depends on sampling method -confounded by necrosis, vascularity MR perfusion [38,43,[53][54][55][56][57][58][59][60][61][62] Higher rCBV in areas of enhancement Studies have correlated rCBV values to tissueconfirmed diagnoses [53] and survival [59] Vascular leak problematic, requires correction; rCBV value cutoffs vary by technique, institution…”