Dataset Information

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

ABSTRACT:

Objective

The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods.

Methods

OA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed.

Results

Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 ?m and the medial osteophyte grew by 0.124±0.028 ?m3. Excellent agreement was found when automated measurements were compared with manual assessments.

Conclusion

Our automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies.

SUBMITTER: Das Neves Borges P

PROVIDER: S-EPMC5363908 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

Das Neves Borges Patricia P Vincent Tonia L TL Marenzana Massimo M

PloS one 20170323 3

<h4>Objective</h4>The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temp ...[more]

PMID: 28334010

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Project description:IntroductionMicro-computed tomography (μCT) is a valuable imaging modality for longitudinal quantification of bone volumes to identify disease or treatment effects for a broad range of conditions that affect bone health. Complex structures, such as the hindpaw with up to 31 distinct bones in mice, have considerable analytic potential, but quantification is often limited to a single bone volume metric due to the intensive effort of manual segmentation. Herein, we introduce a high-throughput, user-friendly, and semi-automated method for segmentation of murine hindpaw μCT datasets.MethodsIn vivo μCT was performed on male (n = 4; 2-8-months) and female (n = 4; 2-5-months) C57BL/6 mice longitudinally each month. Additional 9.5-month-old male C57BL/6 hindpaws (n = 6 hindpaws) were imaged by ex vivo μCT to investigate the effects of resolution and integration time on analysis outcomes. The DICOMs were exported to Amira software for the watershed-based segmentation, and watershed markers were generated automatically at approximately 80% accuracy before user correction. The semi-automated segmentation method utilizes the original data, binary mask, and bone-specific markers that expand to the full volume of the bone using watershed algorithms.ResultsCompared to the conventional manual segmentation using Scanco software, the semi-automated approach produced similar raw bone volumes. The semi-automated segmentation also demonstrated a significant reduction in segmentation time for both experienced and novice users compared to standard manual segmentation. ICCs between experienced and novice users were >0.9 (excellent reliability) for all but 4 bones.DiscussionThe described semi-automated segmentation approach provides remarkable reliability and throughput advantages. Adoption of the semi-automated segmentation approach will provide standardization and reliability of bone volume measures across experienced and novice users and between institutions. The application of this model provides a considerable strategic advantage to accelerate various research opportunities in pre-clinical bone and joint analysis towards clinical translation.

Project description:PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/- ) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.

Dataset Information

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

Objective

Methods

Results

Conclusion

Publications

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

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