Functional MRI can detect changes in intratissue strains in a full thickness and critical sized ovine cartilage defect model

Abstract

Functional imaging of tissue biomechanics can reveal subtle changes in local softening and stiffening associated with disease or repair, but noninvasive and nondestructive methods to acquire intratissue measures in well-defined animal models are largely lacking. We utilized displacement encoded MRI to measure changes in cartilage deformation following creation of a critical-sized defect in the medial femoral condyle of ovine (sheep) knees, a common in situ and large animal model of tissue damage and repair. We prioritized visualization of local, site-specific variation and changes in displacements and strains following defect placement by measuring spatial maps of intratissue deformation. Custom data smoothing algorithms were developed to minimize propagation of noise in the acquired MRI phase data toward calculated displacement or strain, and to improve strain measures in high aspect ratio tissue regions. Strain magnitudes in the femoral, but not tibial, cartilage dramatically increased in load-bearing and contact regions especially near the defect locations, with an average 6.7% ± 6.3%, 13.4% ± 10.0%, and 10.0% ± 4.9% increase in first and second principal strains, and shear strain, respectively. Strain heterogeneity reflected the complexity of the in situ mechanical environment within the joint, with multiple tissue contacts defining the deformation behavior. This study demonstrates the utility of displacement encoded MRI to detect increased deformation patterns and strain following disruption to the cartilage structure in a clinically-relevant, large animal defect model. It also defines imaging biomarkers based on biomechanical measures, in particular shear strain, that are potentially most sensitive to evaluate damage and repair, and that may additionally translate to humans in future studies.

Keywords: Cartilage defect; DualMRI and quantitative MRI; Elastography; Magnetic resonance imaging; Mechanical behavior.

Figure 1. Experimental setup for intact and defect joints

The sheep stifles were placed in an MRI-compatible cyclic loading device to compress joint specimen during the MRI acquisition [A]. The sagittal imaging plane was chosen to overlap with the most distal point of the medial femoral condyle in the load-bearing region of the joint; a representative specimen is shown [B]. After standard MRI scans, preconditioning with cyclic loading and dualMRI (cyclic loading synchronized with displacement encoded MRI) experiments [C] were performed on an intact joint [D]. An 8-mm diameter full-thickness (5 mm) osteochondral defect was created at the most distal aspect of the medial condyle [E] prior to imaging the defect condition. Joints are shown open for illustrative purposes only, and remained closed with all ligaments intact during testing.

Figure 2. Spatial maps of displacements were noninvasively measured in articular cartilage before and following placement of a critical sized defect in the medial femoral condyle

Standard MRI of a representative specimen in intact and defect conditions allowed for the identification of a preserved cartilage-cartilage contact region (red shading), and registration of joint morphology in time-sequence MRI scans [A]. In-plane displacements were computed from dualMRI data [B] and show that rigid body motions dominate displacements in the loading direction (y) and direction transverse to loading (x), revealing little obvious internal spatial variations. [C] The raw displacements were smoothed using a locally-weighted linear regression (LOWESS) method, and showed expected through-thickness gradients, in contrast to Gaussian smoothing.

Figure 3. Spatial patterns of strain in articular cartilage increase and localize following creation of a full thickness defect

In-plane Green-Lagrange strains (E_xx, E_yy, E_xy) were computed from smoothed displacements [A], and first and second principal (E_p1 and E_p2) and maximum shear (E_sm) strains were calculated [B]. High tensile and shear strains were observed at the interface between cartilage-cartilage and cartilage-meniscus contact areas in this representative specimen, with similar high-strain regions observed in other specimens.

Figure 4. Maximum principal strains in cartilage tibia and femur regions of interest, and contact regions

Maximum values for first principal and maximum shear strain, and minimum values for second principal strain were computed for full tibial and femoral regions of interest (ROIs) in the intact and defect conditions [A]. The magnitude of principal strains tended to increase with defect placement in femoral, but not tibial, cartilage. Dramatic increases in the maximum shear strain within the contact region of femoral cartilage indicate a heightened sensitivity of this measure to defect placement and altered mechanics within the joint.