TY - JOUR

T1 - Novel quantitative digital image analysis methodology for assessment of inflammatory changes in MRI data in a post-hoc analysis of data acquired from a phase IIb study of baricitinib in patients with active rheumatoid arthritis

AU - Boesen, M.

AU - Beattie, S. D.

AU - Schlichting, D. E.

AU - Kubassova, O.

N1 - Publisher Copyright: © 2021 Eli Lilly and Company

PY - 2021

Y1 - 2021

N2 - Purpose: To evaluate a novel quantitative methodology to assess inflammatory changes in magnetic resonance imaging (MRI) data from patients with rheumatoid arthritis (RA) and the impact of image quality on imaging outcomes compared to the RA Magnetic Resonance Imaging Score (RAMRIS). Methods: Three-dimensional, T1-weighted, fat-suppressed MRI sequences of the hand/wrist before and after intravenous Gadolinium contrast from patients with RA in a placebo-controlled clinical trial (NCT01185353) were re-evaluated post hoc. The methodology was integrated into proprietary software (DYNAMIKA®) and assessed inflammation through pixelated measurements of the contrast-enhancing (inflammatory) volume. A semi-automatic approach outlined contrast-enhancing synovial tissue in the wrist and second to fifth metacarpophalangeal joints with a rough region of interest (ROI); quantitative imaging biomarkers were generated by means of quantitative total volume of inflammation and quantitative degree of inflammation relative to the signal in a 1 cm in diameter ROI in the center of the thenar or lumbrical muscle for internal reference. The time from Gadolinium injection to finalization of the post-contrast images was calculated from the images’ Digital Imaging and Communications in Medicine header. An experienced reader graded image quality as poor, acceptable, or good. Results: Results from this quantitative methodology, especially when excluding images with poor quality scores (14–32%), provided a more pronounced and monotonically increasing dose-response than the original RAMRIS results on synovitis and osteitis. Conclusions: This computer-aided quantitative scoring method provided continuous measures of inflammatory changes relative to muscle and may be more sensitive and interpretable concerning dose/response separation between RA treatment groups.

AB - Purpose: To evaluate a novel quantitative methodology to assess inflammatory changes in magnetic resonance imaging (MRI) data from patients with rheumatoid arthritis (RA) and the impact of image quality on imaging outcomes compared to the RA Magnetic Resonance Imaging Score (RAMRIS). Methods: Three-dimensional, T1-weighted, fat-suppressed MRI sequences of the hand/wrist before and after intravenous Gadolinium contrast from patients with RA in a placebo-controlled clinical trial (NCT01185353) were re-evaluated post hoc. The methodology was integrated into proprietary software (DYNAMIKA®) and assessed inflammation through pixelated measurements of the contrast-enhancing (inflammatory) volume. A semi-automatic approach outlined contrast-enhancing synovial tissue in the wrist and second to fifth metacarpophalangeal joints with a rough region of interest (ROI); quantitative imaging biomarkers were generated by means of quantitative total volume of inflammation and quantitative degree of inflammation relative to the signal in a 1 cm in diameter ROI in the center of the thenar or lumbrical muscle for internal reference. The time from Gadolinium injection to finalization of the post-contrast images was calculated from the images’ Digital Imaging and Communications in Medicine header. An experienced reader graded image quality as poor, acceptable, or good. Results: Results from this quantitative methodology, especially when excluding images with poor quality scores (14–32%), provided a more pronounced and monotonically increasing dose-response than the original RAMRIS results on synovitis and osteitis. Conclusions: This computer-aided quantitative scoring method provided continuous measures of inflammatory changes relative to muscle and may be more sensitive and interpretable concerning dose/response separation between RA treatment groups.

KW - Baricitinib

KW - Biomarker

KW - Inflammation

KW - MRI

KW - Quantitative imaging

KW - Rheumatoid arthritis

U2 - 10.1016/j.ejrad.2021.109877

DO - 10.1016/j.ejrad.2021.109877

M3 - Journal article

C2 - 34412009

AN - SCOPUS:85112776978

VL - 143

JO - European Journal of Radiology

JF - European Journal of Radiology

SN - 0720-048X

M1 - 109877

ER -