Abstract
The use of rCBV as a response metric in clinical trials has been hampered, in part, due to variations in the biomarker consistency and associated interpretation across sites, stemming from differences in image acquisition and post-processing methods. This study leveraged a dynamic susceptibility contrast magnetic resonance imaging digital reference object to characterize rCBV consistency across 12 sites participating in the Quantitative Imaging Network (QIN), specifically focusing on differences in site-specific imaging protocols (IPs; n = 17), and PMs (n = 19) and differences due to site-specific IPs and PMs (n = 25). Thus, high agreement across sites occurs when 1 managing center processes rCBV despite slight variations in the IP. This result is most likely supported by current initiatives to standardize IPs. However, marked intersite disagreement was observed when site-specific software was applied for rCBV measurements. This study's results have important implications for comparing rCBV values across sites and trials, where variability in PMs could confound the comparison of therapeutic effectiveness and/or any attempts to establish thresholds for categorical response to therapy. To overcome these challenges and ensure the successful use of rCBV as a clinical trial biomarker, we recommend the establishment of qualifying and validating site- and trial-specific criteria for scanners and acquisition methods (eg, using a validated phantom) and the software tools used for dynamic susceptibility contrast magnetic resonance imaging analysis (eg, using a digital reference object where the ground truth is known).
Highlights
The relative cerebral blood volume, derived from dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI), is an established biomarker of glioma status that can aid in diagnosis [1], detecting treatment response [2, 3], guiding biopsies [4, 5], and reliable differentiation of post-treatment radiation effects and tumor progression [6,7,8,9,10]
Eleven centers participated in this project: Barrow Neurological Institute (BNI), Brown University (BU), Massachusetts General Hospital (MGH), Mayo Clinic Arizona (Mayo AZ), Mayo Clinic Minnesota (Mayo MN), Medical College of Wisconsin (MCW), University of Michigan (UM1), The University of Texas Health at San Antonio (UTSA), University of Texas at Austin (UT), University of Texas Southwestern Medical Center at Dallas (UTSW), University of Washington (UW), and Washington University (WashU)
High agreement is observed across sites when a constant postprocessing methods (PMs) is applied to sitespecific imaging protocols (IPs) (ICC ϭ 0.879)
Summary
The relative cerebral blood volume (rCBV), derived from dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI), is an established biomarker of glioma status that can aid in diagnosis [1], detecting treatment response [2, 3], guiding biopsies [4, 5], and reliable differentiation of post-treatment radiation effects and tumor progression [6,7,8,9,10] It is increasingly leveraged as a biomarker of early therapeutic response in Multisite rCBV Consistency Using a DRO clinical trials [11, 12]. Recent imaging protocol (IP) recommendations by the American Society of Functional Neuroradiology (ASFNR) has served as the first step in standardizing DSC-MRI protocols for clinical applications [13] To aid in this effort, 12 institutions within the QIN aimed to investigate and determine the current rCBV reproducibility using a recently developed and validated in silico digital reference object (DRO) that is representative of a wide range of possible glioma magnetic resonance signals [14]. Results from this community-based challenge will help steer standardization of DSC-MRI rCBV protocols with the hope that it can be successfully translated to the clinical setting
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