The Utility of Multi-Stack Alignment and 3D Longitudinal Image Registration to Assess Bone Remodeling in Rheumatoid Arthritis Patients from Second Generation HR-pQCT Scans

Abstract

Background: Medical imaging plays an important role in determining the progression of joint damage in rheumatoid arthritis (RA). High resolution peripheral quantitative computed tomography (HR-pQCT) is a sensitive tool capable of evaluating bone microarchitecture and erosions, and 3D rigid image registration can be used to visualize and quantify bone remodeling over time. However, patient motion during image acquisition can cause a “stack shift” artifact resulting in loss of information and reducing the number of erosions that can be analyzed using HR-pQCT. The purpose of this study was to use image registration to improve the number of useable HR-pQCT scans and to apply image-based bone remodeling assessment to the metacarpophalangeal (MCP) joints of RA patients. Methods: Ten participants with RA completed HR-pQCT scans of the 2 nd and 3 rd MCP joints at enrolment to the study and at a 6-month follow-up interval. At 6-months, an additional repeat scan was acquired to evaluate reliability. HR-pQCT images were acquired in three individual 1 cm acquisitions (stacks) with a 25% overlap. We completed analysis first using standard evaluation methods, and second with multi-stack registration. We assessed whether additional erosions could be evaluated after multi-stack registration. Bone remodeling analysis was completed using registration and transformation of baseline and follow-up images. We calculated the bone formation and resorption volume fractions with 6-month follow-up, and same-day repositioning as a negative control. Results: 13/57 (23%) of erosions could not be analyzed from raw images due to a stack shift artifact. All erosions could be volumetrically assessed after multi-stack registration. We observed that there was a median bone formation fraction of 2.1% and resorption fraction of 3.8% in RA patients over the course of 6 months. In contrast to the same-day rescan negative control, we observed median bone formation and resorption fractions of 0%. Conclusions: Multi-stack image registration is a useful tool to improve the number of useable scans when analyzing erosions using HR-pQCT. Further, image registration can be used to longitudinally assess bone remodeling. These methods could be implemented in future studies to provide important pathophysiological information on the progression of bone damage.

Formation Dominates Resorption With Increasing Mineralized Density and Time Postfracture in Cortical but Not Trabecular Bone: A Longitudinal HRpQCT Imaging Study in the Distal Radius

“…While 3D image registration has previously been applied to fractured radii and the combined use of both image registration and bone remodeling analysis has been applied to patients with diminishing bone quality and rheumatoid arthritis, (9)(10)(11)14) our study is the first to evaluate localized bone remodeling throughout the process of fracture healing in humans. Herein, a multi-density approach was utilized, which parallels recent analysis of bone remodeling in animal fracture healing and allows for differentiation between low-and high-density remodeling.…”

“…For reference, we have included analysis of our data using the thresholded difference methods of Brunet et al to support the following discussion on methodological differences (Figure 8). (11) Due to the increased density of the cortical bone, the thresholded difference method is much more likely to identify image noise in higher density bone as either formation or resorption, resulting in equivalent or even higher formation and resorption volume fractions in the cortical region than in the trabecular region. This increased formation and resorption in the cortical region can be observed visually in the recent study of bone remodeling in the metacarpophalangeal joint.…”

“…This increased formation and resorption in the cortical region can be observed visually in the recent study of bone remodeling in the metacarpophalangeal joint. (11) We were specifically interested in investigating fracture healing in both the trabecular and cortical compartments of the distal radius, thus we chose to instead use a multidensity approach which highlights observed differences at multiple density thresholds. Using this approach, formation and resorption were observed to be lower in the cortical region than the trabecular region, which agrees with our understanding of of both fracture healing and bone remodeling, whereby callus mineralization results in low density remodeling and trabecular bone turnover is generally greater than that of cortical bone.…”

“…While bone formation rate (BFR) and bone resorption rate (BRR) have been the standard in reporting dynamic morphometry in animal studies, (12,21,22) the investigation of remodeling in humans has instead used formation and resorption bone volume fractions, which do not include the aspect of time between evaluated images. (9)(10)(11) While the specific reasoning behind this decision is unknown, the increased image noise of lower resolution clinical images from HR-pQCT, in comparison to micro CT images, would result in greater false positive and false negative remodeling events. Thus, the calculation of rates of change, such as BFR and BRR, would be biased to the time interval between measurements.…”

“…( 8 ) Longitudinal imaging and 3D‐image registration are tools provided in the scanner software, but have yet to be adopted into the standard patient evaluation for HRpQCT images. Although these techniques have allowed for quantification of localized microstructural remodeling in cohorts of 10 or fewer patients with decreased bone quality and disease, ( 9–11 ) the methods used to date in patients have diverged from the methods used to quantify formation and resorption in animal studies ( 12,13 ) and have been inconsistent in the specific parameters used for quantification of remodeling (i.e., mineral density‐based thresholds and noise reduction techniques). However, concurrent research has also shown that 3D‐image registration can be applied to fractured radii and even help to monitor changes in BMD in localized regions of the fracture.…”