Osteoarthritis (OA) is a potentially debilitating condition of articular joints characterized by a gradual but progressive degradation of the cartilage extracellular matrix. Interest in OA pathogenesis and in models for testing disease modifying therapies has motivated the development of numerous small animal models for joint degeneration. However, while matrix changes in such models can be evaluated via histology and gross biochemical analysis, determination of detailed spatial information regarding matrix changes is challenging at best. A technique capable of high resolution, nondestructive quantification of cartilage morphology and matrix composition could revolutionize the evaluation of such small animal models. The goal of this Exploratory/Developmental Research Grant proposal is to develop a novel imaging methodology utilizing contrast-enhanced microcomputed tomography (UCT) to obtain high resolution, three-dimensional (3D) data describing the morphology and sulfated glycosaminoglycan distribution of small animal articular cartilage. While a powerful tool for quantitative morphological and microstructural analysis of bone and a variety of biomaterials, UCT has not been useful for analysis of cartilage or other soft tissues because of their minimal X-ray attenuation. We have recently performed preliminary validation of a novel UCT application for quantification of the Equilibrium Partitioning of an Ionic Contrast agent UCT (EPIC-UCT) that relies on preferential exclusion of a negatively charged, radio-opaque contrast agent from tissue regions with a greater negative fixed charge density (primarily due to sulfated glycosaminoglycans (sGAGs) on proteoglycans).
The specific aims of the proposed research are to (1) evaluate the use of EPIC-UCT to quantify the morphology of rat articular cartilage; (2) evaluate the use of EPIC-UCT to quantify the sGAG distribution of rat articular cartilage; and (3) evaluate the use of EPIC-UCT for in situ evaluation of articular cartilage in intact rat knees using direct intraarticular injection of the contrast agent. In this 2-year project, we aim to develop a methodology suitable for end-stage analysis of articular cartilage in small rodent models and to have laid the groundwork for studies extending this methodology to longitudinal, in vivo tracking of cartilage matrix changes. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR053716-02
Application #
7230164
Study Section
Special Emphasis Panel (ZRG1-MOSS-A (02))
Program Officer
Tyree, Bernadette
Project Start
2006-05-01
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2007
Total Cost
$157,325
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Xie, LiQin; Lin, Angela S P; Kundu, Kousik et al. (2012) Quantitative imaging of cartilage and bone morphology, reactive oxygen species, and vascularization in a rodent model of osteoarthritis. Arthritis Rheum 64:1899-908
Xie, L; Lin, A S P; Guldberg, R E et al. (2010) Nondestructive assessment of sGAG content and distribution in normal and degraded rat articular cartilage via EPIC-microCT. Osteoarthritis Cartilage 18:65-72
Gemmiti, Christopher V; Guldberg, Robert E (2009) Shear stress magnitude and duration modulates matrix composition and tensile mechanical properties in engineered cartilaginous tissue. Biotechnol Bioeng 104:809-20
Xie, L; Lin, A S P; Levenston, M E et al. (2009) Quantitative assessment of articular cartilage morphology via EPIC-microCT. Osteoarthritis Cartilage 17:313-20
Guldberg, Robert E; Duvall, Craig L; Peister, Alexandra et al. (2008) 3D imaging of tissue integration with porous biomaterials. Biomaterials 29:3757-61
Palmer, Ashley W; Guldberg, Robert E; Levenston, Marc E (2006) Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography. Proc Natl Acad Sci U S A 103:19255-60