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

• Published in: Tomography (Ann Arbor) Vol. 9; no. 2; pp. 552 - 566
• Main Authors: Ross, Brian D, Malyarenko, Dariya, Heist, Kevin, Amouzandeh, Ghoncheh, Jang, Youngsoon, Bonham, Christopher A, Amirfazli, Cyrus, Luker, Gary D, Chenevert, Thomas L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.02.2023; MDPI
• Subjects: Animals; apparent diffusion coefficient, ADC; Biomarkers; Bone Marrow - diagnostic imaging; bone marrow, BM; Hematopoietic stem cells; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mice; murine model of myelofibrosis, MF; Primary Myelofibrosis - diagnostic imaging; quantitative imaging biomarker, QIB; quantitative MRI; repeatability; Tibia - diagnostic imaging; repeatability; apparent diffusion coefficient, ADC; magnetization transfer ratio, MTR; murine model of myelofibrosis, MF; quantitative MRI; quantitative imaging biomarker, QIB; bone marrow, BM; proton density fat fraction, PDFF
• ISSN: 2379-139X; 2379-1381; 2379-139X
• DOI: 10.3390/tomography9020045

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) μm /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.