Effect of aging on tibiofemoral cartilage and meniscus stiffness constant

Abstract

Purpose: Current clinical diagnostics of knee osteoarthritis (OA) are ineffective at detecting and monitoring early signs of joint degeneration. Measuring the deformation of knee soft tissue under loading could provide a more sensitive measure to detect OA earlier in the disease process. The objective of this research was to develop a novel in-vivo method to determine a cartilage-meniscus (C-M) stiffness constant using dual fluoroscopy (DF) and magnetic resonance (MR) imaging. Further, this study investigated the hypothesis that a C-M constant differs significantly with age in healthy males, with the goal of using these healthy participants as age-matched controls in further clinical research. Methods: Ten healthy males (n=5, 20-30 yrs old; n=5, 50-60 yrs old) with no history of lower limb injury or surgery volunteered for participation. The study was approved by the local ethics board (REB15-0554) and informed consent was obtained for all participants. Participants were non-weight bearing for a minimum of one hour prior to MR imaging. A high resolution MR scan (3T Discovery 750, GE USA) was conducted to generate subject-specific 3D bone and cartilage models in Amira (FES, Germany); scan parameters: slice thickness 1 mm; between slice spacing 0.5 mm; field of view 24x24 cm; matrix 512x512 pixels; number of slices 200; echo time 2.32 ms; repetition time 7.513 ms; flip angle 35°; acquisition time 2ʹ45ʺ. Thereafter, participants were assisted by wheelchair to the DF lab, where they were fit with a custom knee brace. Participants stood on the contralateral limb and shifted their weight to the test limb on instruction. Standing weight bearing DF images (0.155 mm x 0.155 mm) were collected at 20 Hz for 5 min (1 min continuously, 30 sec intervals [2 sec duration each] for the remaining 4 minutes). Image distortion correction and calibration was conducted using software tools by Brown University, USA and custom written code in Matlab (v2016b, MathWorks, USA). Bone kinematics were reconstructed using 2D-3D registration in Joint Track Biplane (University of Florida, USA). Bone kinematics obtained from registration were then applied to co-registered cartilage models to calculate cartilage motion. C-M deformations were estimated as the change in median proximity of all femoral cartilage model faces, with respect to the tibial cartilage, at each DF frame collected. Ground reaction forces were collected using an instrumented treadmill (Bertec, USA). The force acting at the knee was determined as the vertical ground reaction force minus the weight applied by the foot and shank of the imaged limb. The C-M constant (analogous to a measure of soft tissue stiffness during continuous loading) was calculated as the median change in force divided by the change in median proximity. This median value was calculated between 10 seconds and 5 minutes of the standing loading trial. A 2-tailed Mann Whitney U non-parametric t-test was performed in SPSS to determine differences between the C-M constant between younger and older age groups. Results: C-M constant was found to significantly increase by 12.51 N/mm (p=0.009) with age. The 20-30 year old group median was 3.39 N/mm (interquartile range (IQR)=2.01-7.29 N/mm) while the 50-60 year old group median was 15.90 N/mm (IQR=11.35-21.17 N/mm) (Figure 1). Conclusions: The finding of a significant increase in the C-M stiffness constant with age indicates this novel in-vivo measure may be a sensitive tool for detecting differences in soft-tissue mechanical properties. Greater variance in the C-M stiffness value in the older group may also demonstrate greater variability in cartilage mechanical properties with age. Further research will be conducted to validate the C-M constant methodology using a porcine joint model to inform future clinical research applications.