Rapid, automated imaging of mouse articular cartilage by microCT for early detection of osteoarthritis and finite element modelling of joint mechanics
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Published version
Author(s)
Borges, P Das Neves
Forte, AE
Vincent, TL
Dini, D
Marenzana, M
Type
Journal Article
Abstract
Objective
Mouse articular cartilage (AC) is mostly assessed by histopathology and its mechanics is poorly characterised. In this study: (1) we developed non-destructive imaging for quantitative assessment of AC morphology and (2) evaluated the mechanical implications of AC structural changes.
Methods
Knee joints obtained from naïve mice and from mice with osteoarthritis (OA) induced by destabilization of medial meniscus (DMM) for 4 and 12 weeks, were imaged by phosphotungstic acid (PTA) contrast enhanced micro-computed tomography (PTA-CT) and scored by conventional histopathology. Our software (Matlab) automatically segmented tibial AC, drew two regions centred on each tibial condyle and evaluated the volumes included. A finite element (FE) model of the whole mouse joint was implemented to evaluate AC mechanics.
Results
Our method achieved rapid, automated analysis of mouse AC (structural parameters in <10 h from knee dissection) and was able to localise AC loss in the central region of the medial tibial condyle. AC thickness decreased by 15% at 4 weeks and 25% at 12 weeks post DMM surgery, whereas histopathology scores were significantly increased only at 12 weeks. FE simulations estimated that AC thinning at early-stages in the DMM model (4 weeks) increases contact pressures (+39%) and Tresca stresses (+43%) in AC.
Conclusion
PTA-CT imaging is a fast and simple method to assess OA in murine models. Once applied more extensively to confirm its robustness, our approach will be useful for rapidly phenotyping genetically modified mice used for OA research and to improve the current understanding of mouse cartilage mechanics.
Mouse articular cartilage (AC) is mostly assessed by histopathology and its mechanics is poorly characterised. In this study: (1) we developed non-destructive imaging for quantitative assessment of AC morphology and (2) evaluated the mechanical implications of AC structural changes.
Methods
Knee joints obtained from naïve mice and from mice with osteoarthritis (OA) induced by destabilization of medial meniscus (DMM) for 4 and 12 weeks, were imaged by phosphotungstic acid (PTA) contrast enhanced micro-computed tomography (PTA-CT) and scored by conventional histopathology. Our software (Matlab) automatically segmented tibial AC, drew two regions centred on each tibial condyle and evaluated the volumes included. A finite element (FE) model of the whole mouse joint was implemented to evaluate AC mechanics.
Results
Our method achieved rapid, automated analysis of mouse AC (structural parameters in <10 h from knee dissection) and was able to localise AC loss in the central region of the medial tibial condyle. AC thickness decreased by 15% at 4 weeks and 25% at 12 weeks post DMM surgery, whereas histopathology scores were significantly increased only at 12 weeks. FE simulations estimated that AC thinning at early-stages in the DMM model (4 weeks) increases contact pressures (+39%) and Tresca stresses (+43%) in AC.
Conclusion
PTA-CT imaging is a fast and simple method to assess OA in murine models. Once applied more extensively to confirm its robustness, our approach will be useful for rapidly phenotyping genetically modified mice used for OA research and to improve the current understanding of mouse cartilage mechanics.
Date Issued
2014-10-01
Date Acceptance
2014-07-12
Citation
Osteoarthritis and Cartilage, 2014, 22 (10), pp.1419-1428
ISSN
1063-4584
Publisher
Elsevier
Start Page
1419
End Page
1428
Journal / Book Title
Osteoarthritis and Cartilage
Volume
22
Issue
10
Copyright Statement
© 2014 Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International. This is
an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)
an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)
License URL
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343139800010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
088844/Z/09/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Orthopedics
Rheumatology
Mouse articular cartilage
Destabilisation of medial meniscus model
Micro computed tomography
High-throughput automated image analysis
3-dimensional quantitative imaging
PHOSPHOTUNGSTIC ACID
CONTRAST AGENT
BONE
CT
VISUALIZATION
ARTHROGRAPHY
PROGRESSION
MORPHOLOGY
INITIATION
ADAMTS-5
Publication Status
Published
Date Publish Online
2014-09-30