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Collaborations

ITE-MPM for Cartilage Diagnostics
Lisa A. Fortier, Assistant Professor of Surgery, Department of Clinical Sciences, Cornell University.
Hollis G. Potter, MD, Chief of Resonance Imaging, Hospital for Special Surgery.
Funding: The Stowe Foundation (7/06-6/10).

Dr. Fortier’s research is focused on developing a method for the restoration of damaged articular cartilage to near normal after injury for preventing the onset of osteoarthritis (Fortier et al, 2007; Semevolos, et al, 2006; Gratz et al, 2006). Cartilage implants require cells, growth factors, and scaffolding, and the repair technique should be implementable at the time of diagnosis, rather than after a long and costly tissue culture expansion. The technique should also be purely autogenous in nature to avoid disease transmission and potential immune rejection. This collaboration is focused on ex vivo cartilage characterization, but with a future goal of in vivo cartilage imaging with the development of the MPM arthroscope.

We have initially focused on collagen structure and orientation and autofluorescence characteristics that may offer signature information concerning the underlying pathophysiology of various cartilage lesions. In particular collagen-associated autofluorescence may yield information regarding both normal and abnormal collagen crosslinking and autofluorescent nodules may be diagnostic of osteoarthritic cartilage. In anticipation of an SHG arthroscope, we have made an effort to evaluate SHG cartilage imaging with respect to established diagnostic methods by a direct MRI to MPM imaging comparison. We currently have specimens from twelve horses that received engineered cartilage implants. These consisted of full-thickness cartilage defects filled with bone marrow aspirate concentrate that was polymerized in situ with thrombin under helium arthroscopy. After eight months, the horses were euthanized and their femurs imaged using 3 Tesla, T2-weighted MRI to assess collagen and proteoglycan content (Fig 1a). This data will be compared with both unlabeled fixed sections using MPM (Fig. 1b-e) and with standard histological stained sections using a classic Mankin Scoring of articular cartilage. We will adapt previously developed image analysis algorithms for automatically measuring collagen density and organization in the MPM images.

The long-term goal of DRBIO in this collaboration is to develop a cartilage MPM endo-microscope that can be used as a tool by orthopaedic surgeons to provide important prognostic information regarding the health of the patient’s articular cartilage. In the meantime, we are carrying out exploratory studies on fresh explants from euthanized horses. The development of prototype devices will be designed to mimic existing arthroscopic instrumentation and optimized according to important ITE signatures identified in the ex vivo studies. Initial imaging trials will be conducted on anesthetized horses already scheduled for euthanasia. Development of a multiphoton arthroscope is underway and the combined expertise and close proximity of DRBIO and the College of Veterinary Medicine will greatly facilitate the development of such instrumentation. Identification of key autofluorescent signatures is also a critical core research area for this collaboration.

References

Fortier, L.A., L.V. Schnabel, H.O. Mohammed, and K.G. Mayr (2007) Assessment of cartilage degradation effects of matrix metalloproteinase-13 in equine cartilage cocultured with synoviocytes. Am J Vet Res 68(4):379-384.

Semevolos, S.A., A.J. Nixon, L.A. Fortier, M.L. Strassheim, and J. Haupt (2006) Age-related expression of molecular regulators of hypertrophy and maturation in articular cartilage. J Orthop Res 24(8):1773-1781.

Gratz, K.R., V.W. Wong, A.C. Chen, L.A. Fortier, A.J. Nixon, and R.L. Sah (2006) Biomechanical assessment of tissue retrieved after in vivo cartilage defect repair: tensile modulus of repair tissue and integration with host cartilage. J Biomech 39(1):138-146.

 

 

 



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