Contrast enhanced μCT imaging of early articular changes in a pre-clinical model of osteoarthritis

D S Reece; T Thote; A S P Lin; N J Willett; R E Guldberg

doi:10.1016/j.joca.2017.10.017

Contrast enhanced μCT imaging of early articular changes in a pre-clinical model of osteoarthritis

Osteoarthritis Cartilage. 2018 Jan;26(1):118-127. doi: 10.1016/j.joca.2017.10.017. Epub 2017 Oct 28.

Authors

D S Reece¹, T Thote², A S P Lin³, N J Willett⁴, R E Guldberg⁵

Affiliations

¹ Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA. Electronic address: [email protected].
² Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA. Electronic address: [email protected].
³ George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA. Electronic address: [email protected].
⁴ Department of Orthopaedics, Emory University, Atlanta Veteran's Affairs Medical Center, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA. Electronic address: [email protected].
⁵ George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA. Electronic address: [email protected].

PMID: 29107695
DOI: 10.1016/j.joca.2017.10.017

Abstract

Objective: The objective of this study was to characterize early osteoarthritis (OA) development in cartilage and bone tissues in the rat medial meniscus transection (MMT) model using non-destructive equilibrium partitioning of an ionic contrast agent micro-computed tomography (EPIC-μCT) imaging. Cartilage fibrillation, one of the first physiological developments in OA, was quantified in the rat tibial plateau as three-dimensional (3D) cartilage surface roughness using a custom surface-rendering algorithm.

Methods: Male Lewis rats underwent MMT or sham-operation in the left leg. At 1- and 3-weeks post-surgery, the animals (n = 7-8 per group) were euthanized and the left legs were scanned using EPIC-μCT imaging to quantify cartilage and bone parameters. In addition, a custom algorithm was developed to measure the roughness of 3D surfaces. This algorithm was validated and used to quantify cartilage surface roughness changes as a function of time post-surgery.

Results: MMT surgery resulted in significantly greater cartilage damage and subchondral bone sclerosis with the damage increasing in both severity and area from 1- to 3-weeks post-surgery. Analysis of rendered 3D surfaces could accurately distinguish early changes in joints developing OA, detecting significant increases of 45% and 124% in surface roughness at 1- and 3-weeks post-surgery respectively.

Conclusion: Disease progression in the MMT model progresses sequentially through changes in the cartilage articular surface, extracellular matrix composition, and then osteophyte mineralization and subchondral bone sclerosis. Cartilage surface roughness is a quantitative, early indicator of degenerative joint disease in small animal OA models and can potentially be used to evaluate therapeutic strategies.

Keywords: Cartilage fibrillation; EPIC-μCT; Joint degeneration; MMT; Osteoarthritis; Surface roughness.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Algorithms
Animals
Arthritis, Experimental / diagnostic imaging
Arthritis, Experimental / pathology
Bone Diseases / diagnostic imaging
Bone Diseases / pathology*
Cartilage Diseases / diagnostic imaging
Cartilage Diseases / pathology*
Disease Models, Animal
Disease Progression
Lower Extremity / surgery
Male
Organ Size
Osteoarthritis, Knee / diagnostic imaging
Osteoarthritis, Knee / pathology*
Osteophyte / diagnostic imaging
Osteophyte / pathology
Rats, Inbred Lew
X-Ray Microtomography / methods