Repeatability of Quantitative Magnetic Resonance Imaging Biomarkers in the Tibia Bone Marrow of a Murine Myelofibrosis Model

Abstract

Quantitative MRI biomarkers are sought to replace painful and invasive sequential bone-marrow biopsies routinely used for myelofibrosis (MF) cancer monitoring and treatment assessment. Repeatability of MRI-based quantitative imaging biomarker (QIB) measurements was investigated for apparent diffusion coefficient (ADC), proton density fat fraction (PDFF), and magnetization transfer ratio (MTR) in a JAK2 V617F hematopoietic transplant model of MF. Repeatability coefficients (RCs) were determined for three defined tibia bone-marrow sections (2–9 mm; 10–12 mm; and 12.5–13.5 mm from the knee joint) across 15 diseased mice from 20–37 test-retest pairs. Scans were performed on consecutive days every two weeks for a period of 10 weeks starting 3–4 weeks after transplant. The mean RC with (95% confidence interval (CI)) for these sections, respectively, were for ADC: 0.037 (0.031, 0.050), 0.087 (0.069, 0.116), and 0.030 (0.022, 0.044) μm2/ms; for PDFF: 1.6 (1.3, 2.0), 15.5 (12.5, 20.2), and 25.5 (12.0, 33.0)%; and for MTR: 0.16 (0.14, 0.19), 0.11 (0.09, 0.15), and 0.09 (0.08, 0.15). Change-trend analysis of these QIBs identified a dynamic section within the mid-tibial bone marrow in which confident changes (exceeding RC) could be observed after a four-week interval between scans across all measured MRI-based QIBs. Our results demonstrate the capability to derive quantitative imaging metrics from mouse tibia bone marrow for monitoring significant longitudinal MF changes.

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

“…These challenges include increasing SNR, reducing motion artifacts, optimizing protocols for improving repeatability and reproducibility, and improving sensitivity and specificity. Several manuscripts in this special issue contributed by the CIRP teams present the progress on the development of new technology and methodology [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

“…MR imaging the BM in the mouse tibias is challenging due to the small size (1 mm diameter) that limits the SNR, and thus the accuracy of quantitative imaging biomarkers. Using a cryo-cooled MRI to receive coil for SNR improvement, Ross et al successfully investigated the repeatability measures of quantitative imaging metrics for the tibia GEMMs of myelofibrosis, including FF, ADC, and MTR methods [ 33 ]. MR imaging of PDAC in GEMMs suffers from respiratory motion and increased magnetic susceptibility artifacts at high magnetic fields.…”

Biomarkers of Cartilage Composition

“…For intermediate ADC values, the variability across scans was higher than that for regions of higher or lower ADC value, which could also be due to differential evolution over time. 67 In a prospective pilot study of pediatric patients, 68 IVIM has shown promising results as an alternative diagnosing technique to contrast-enhanced MRI for identifying or ruling out knee synovitis. Interrater agreement for contrast-enhanced MRI and DWI was perfect (κ ¼1) for identifying synovitis and substantial (κ ¼ 0.655) for determining the degree of synovial enhancement.…”