Comparison of novel clinically applicable methodology for sensitive diagnostics of cartilage degeneration

Abstract

In order efficiently to target therapies intending to stop or reverse degenerative processes of articular cartilage, it would be crucial to diagnose osteoarthritis (OA) earlier and more sensitively than is possible with the existing clinical methods. Unfortunately, current clinical methods for OA diagnostics are insensitive for detecting the early degenerative changes, e.g., arising from collagen network damage or proteoglycan depletion. We have recently investigated several novel quantitative biophysical methods, including ultrasound indentation, quantitative ultrasound techniques and magnetic resonance imaging, for diagnosing the degenerative changes of articular cartilage, typical for OA. In this study, the combined results of these novel diagnostic methods were compared with histological (Mankin score, MS), compositional (proteoglycan, collagen and water content) and mechanical (dynamic and equilibrium moduli) reference measurements of the same bovine cartilage samples. Receiver operating characteristics (ROC) analysis was conducted to judge the diagnostic performance of each technique. Indentation and ultrasound techniques provided the most sensitive measures to differentiate samples of intact appearance (MS= 0) from early (1<MS<3) or more advanced (MS>3) degeneration. Furthermore, these techniques were good predictors of tissue composition and mechanical properties. The specificity and sensitivity analyses revealed that the mechano-acoustic methods, when further developed for in vivo use, may provide more sensitive probes for OA diagnostics than the prevailing qualitative X-ray and arthroscopic techniques. Noninvasive quantitative MRI measurements showed slightly lower diagnostic performance than mechano-acoustic techniques. The compared methods could possibly also be used for the quantitative monitoring of success of cartilage repair.

Comparison of single-phase isotropic elastic and fibril-reinforced poroelastic models for indentation of rabbit articular cartilage

“…Several previous studies suggest that the short-term indentation modulus reflects properties of the collagen network, sensitively disrupted in OA, especially at the superficial tissue layers (Garcia-Seco et al, 2005;Kiviranta et al, 2007;Rieppo et al, 2003). Both collagen content and orientation affect the mechanical tissue response (Julkunen et al, 2008b;Kiviranta et al, 2006).…”

“…Using a mechanical indentation test, the mechanical properties of articular cartilage can be determined in vivo or in situ (Appleyard et al, 2001;Bae et al, 2003;Franz et al, 2001;Garcia-Seco et al, 2005;Kiviranta et al, 2007;Lyyra et al, 1999). In clinical diagnostics of OA, rapid measurements are essential and the mechanical properties of the tissue can be estimated using arthroscopic indentation instruments (Appleyard et al, 2001;Brown et al, 2007;Lyyra et al, 1995Lyyra et al, , 1999Niederauer et al, 2004).…”

Contribution of tissue composition and structure to mechanical response of articular cartilage under different loading geometries and strain rates

“…However, these imaging techniques alone are unable to quantify changes in the functional properties of the cartilage, sensitively impaired in early osteoarthritis (OA) (Kiviranta et al 2008;Saarakkala et al 2003). The changes in functional properties of the tissue can be revealed by experimental mechanical tests, or by combining quantitative imaging with mechanical tests or a valid computational model (Franz et al 2001;Julkunen et al 2007;Kiviranta et al 2007;Parsons and Black 1987;Sah et al 1997). Thus, mechanical testing of the tissue is of great interest in studies that aim for more sensitive diagnostics of OA.…”

“…The relationships between the mechanical properties and microscopically determined composition and structure of articular cartilage have been addressed in previous studies (Julkunen et al 2007;Kempson et al 1970;Kiviranta et al 2006;Wayne et al 2003). Indentation testing is a common technique to determine the functional integrity of articular cartilage in vivo (Appleyard et al 2001;Brown et al 2007;Kiviranta et al 2007;Saarakkala et al 2003).…”

A Novel Indicator for Quantitative Assessment of Articular Cartilage Degeneration Using Ultrasound

“…In order to detect OA-induced degenerative changes in hyaline cartilage, different methods have been proposed, including arthroscopy, MRI, ultrasound, etc. [2,3] Ultrasound methods have the potential to assess the state of cartilage degeneration nondestructively. Conventional ultrasonography can reveal structural changes of joint due to osteoarthritis, but it is limited by low resolution and the diagnostic is highly subjective.…”