Vol. 3 No. 2 - June 2017

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Characterizing the Influence of Preload Dosing on Percent Signal Recovery (PSR) and Cerebral Blood Volume (CBV) Measurements in a Patient Population With High-Grade Glioma Using Dynamic Susceptibility Contrast MRI Laura C. Bell 1 , Leland S. Hu 2 , Ashley M. Stokes 1 , Samuel C. McGee 1 , Leslie C. Baxter 1 , and C. Chad Quarles 1 1 Division of Imaging Research, Barrow Neurological Institute, Phoenix, Arizona; and 2 Department of Radiology, Mayo Clinic Arizona, Scottsdale, Arizona Corresponding Author: C. Chad Quarles, PhD Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85018; E-mail: Key Words: DSC-MRI, percent signal recovery, relative cerebral blood volume, preload doses Abbreviations: Dynamic susceptibility contrast–magnetic resonance imaging (DSC-MRI), percent signal recovery (PSR), relative cerebral blood volume (rCBV), contrast agent (CA), blood– brain barrier (BBB), signal intensity (SI), echo times (TE), flip angles (FA), Boxerman–Schmainda– Weiskoff (BSW), regions of interest (ROIs), repetition time (TR), normal-appearing white matter (NAWM), intraclass correlation coefficient (ICC) With DSC-MRI, contrast agent leakage effects in brain tumors can either be leveraged for percent signal re- covery (PSR) measurements or be adequately resolved for accurate relative cerebral blood volume (rCBV) measurements. Leakage effects can be dimished by administration of a preload dose before imaging and/or specific postprocessing steps. This study compares the consistency of both PSR and rCBV measurements as a function of varying preload doses in a retrospective analysis of 14 subjects with high-grade gliomas. The scans consisted of 6 DSC-MRI scans during 6 sequential bolus injections (0.05 mmol/kg). Mean PSR was calculated for tumor and normal-appearing white matter regions of interest. DSC-MRI data were corrected for leakage effects before computing mean tumor rCBV. Statistical differences were seen across varying pre- loads for tumor PSR (P value 5 4.57E-24). Tumor rCBV values did not exhibit statistically significant differences across preloads (P value 5 .14) and were found to be highly consistent for clinically relevant preloads (intraclass correlation coefficient 5 0.93). For a 0.05 mmol/kg injection bolus and pulse sequence parameters used, the highest PSR contrast between normal-appearing white matter and tumor occurs when no preload is used. This suggests that studies using PSR as a biomarker should acquire DSC-MRI data without preload. The find- ing that leakage-corrected rCBV values do not depend on the presence or dose of preload contradicts that of previous studies with dissimilar acquisition protocols. This further confirms the sensitivity of rCBV to preload dosing schemes and pulse sequence parameters and highlights the importance of standardization efforts for achieving multisite rCBV consistency. INTRODUCTION Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI)-based percent signal recovery (PSR) and relative cerebral blood volume (rCBV) measurements have been exten- sively researched as biomarkers to aid in diagnosis (1), assess treatment response (2, 3), obtain improved image-guided biop- sies (4, 5), and to differentiate between posttreatment radiation effects (6, 7) and glioma progression (8-10). However, contrast agent (CA) extravasation is prevalent in subjects with brain cancer because of the breakdown of the blood– brain barrier (BBB), and it is known to confound reliable cerebral blood volume estimation. CA extravasation induces local T1 and T2* leakage effects that alter the measured DSC signal intensity (SI) time curves (11-13). Postcontrast SI time points may either increase (because of T1 effects) or decrease (because of addi- tional T2* effects) relative to precontrast time points based on these leakage effects. The magnitude and influence of these CA leakage effects on PSR and rCBV depend on image acquisition parameters (14-17), CA preload dosing (13, 18), and/or leakage- correction postprocessing methods (12, 19-21). Preload dosing involves the injection of CA several minutes before the bolus injection used for acquisition of DSC-MRI data. The goal of preload dosing is to sufficiently decrease the local tissue T1, such that subsequent CA injections induce only minor RESEARCH ARTICLE ABSTRACT © 2017 The Authors. Published by Grapho Publications, LLC This is an open access article under the CC BY-NC-ND license ( ISSN 2379-1381 TOMOGRAPHY.ORG | VOLUME 3 NUMBER 2 | JUNE 2017 89

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