Evaluation of Apparent Diffusion Coefficient Repeatability and Reproducibility for Preclinical MRIs Using Standardized Procedures and a Diffusion-Weighted Imaging Phantom

Abstract

Relevant to co-clinical trials, the goal of this work was to assess repeatability, reproducibility, and bias of the apparent diffusion coefficient (ADC) for preclinical MRIs using standardized procedures for comparison to performance of clinical MRIs. A temperature-controlled phantom provided an absolute reference standard to measure spatial uniformity of these performance metrics. Seven institutions participated in the study, wherein diffusion-weighted imaging (DWI) data were acquired over multiple days on 10 preclinical scanners, from 3 vendors, at 6 field strengths. Centralized versus site-based analysis was compared to illustrate incremental variance due to processing workflow. At magnet isocenter, short-term (intra-exam) and long-term (multiday) repeatability were excellent at within-system coefficient of variance, wCV [±CI] = 0.73% [0.54%, 1.12%] and 1.26% [0.94%, 1.89%], respectively. The cross-system reproducibility coefficient, RDC [±CI] = 0.188 [0.129, 0.343] µm2/ms, corresponded to 17% [12%, 31%] relative to the reference standard. Absolute bias at isocenter was low (within 4%) for 8 of 10 systems, whereas two high-bias (>10%) scanners were primary contributors to the relatively high RDC. Significant additional variance (>2%) due to site-specific analysis was observed for 2 of 10 systems. Base-level technical bias, repeatability, reproducibility, and spatial uniformity patterns were consistent with human MRIs (scaled for bore size). Well-calibrated preclinical MRI systems are capable of highly repeatable and reproducible ADC measurements.

Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study

“…Moreover, the mean intersite agreements were also good for static vials. The ADC repeatability and ADC reproducibility reported in this study were comparable to those reported in the multisite and multivendor study conducted by Malyarenko et al 35 for an ice-water phantom, although the difference in the materials of the phantom should be noted.…”

“…The repeatability (intraday) and reproducibility (interday) of the ADC and IVIM parameters for the PVP, water and flow tubes were calculated via the within‐system coefficient of variation (wCV) 35 as: where and are paired measurements.…”

Co-Clinical Imaging Metadata Information (CIMI) for Cancer Research to Promote Open Science, Standardization, and Reproducibility in Preclinical Imaging

“…Provisions for those attributes are already included in the DICOM standard, but their implementation and adoption is limited. A recent IADP-wide ADC-phantom round-robin (see article by Malyarenko et al [ 31 ] in the corresponding Special Issue) revealed that these essential elements are missing from the current DICOM implementations on animal scanners across multiple sites, leading to (correctable) technical variability in quantitative ADC measurements. In the case of inadequate metadata and/or conformance from vendors, we are also exploring the ability of the research community to develop tools to manipulate the DICOM metadata.…”

The National Cancer Institute’s Co-Clinical Quantitative Imaging Research Resources for Precision Medicine in Preclinical and Clinical Settings

“…The CIRP network worked to reach consensus on key issues since 2019, including animal model selection, co-clinical study design, standardization of co-clinical instruments, harmonization of co-clinical imaging acquisition, and data analysis pipelines [ 28 ]. This special issue provides a snapshot of current issues and consensus that were explored by the WGs [ 29 , 30 , 31 , 32 ]. The AMCT WG conducted a survey across the CIRP network to identify challenges in using animal models, including PDXs, GEMMs, and transplantable mouse models in co-clinical trial settings, to seek consensus on best practices for employing animal models in co-clinical imaging [ 29 ].…”

“…The PIPs include preclinical imaging claims, imaging process specification, animal model specification, quantitative metrics, and supporting data. The IADP WG also completed a multi-site ADC phantom study on 10 preclinical MRI systems (seven sites, three vendors, and six field strengths), to establish the accuracy (bias), precision (repeatability), and reproducibility of preclinical ADC MRIs [31]. The IMOR WG collected descriptions of the CIRP projects and defined a list of data collection items for CIRP web resources, which are publicly available at the CIRPHub (https://ncihub.org/groups/cirphub/collections/ cirp-web-accessible-resources, accessed on 20 April 2023).…”