PURPOSE

To study the sensitivity to degenerative cartilage changes at two and eight weeks after ACLT¹ for several quantitative MRI parameters, including T₁, T₂, continuous wave T_1ρ (CWT_1ρ), adiabatic T_1ρ (AdT_1ρ) and T_2ρ (AdT_2ρ)² and T_RAFF (relaxation along a fictitious field)³.

METHODS

ACLT was surgically induced in the knees of skeletally mature New Zealand White rabbits. The rabbits were 12 months of age at the beginning of the experiment, when unilateral anterior cruciate ligament transection (ACLT) was performed on 14 rabbits. Snapshots of disease progression were captured by sacrificing animals at two weeks (2ACLT, n=8) and eight weeks (8ACLT, n=6) after surgery. An additional 16 non-operated rabbits served as control. Femoral condyles and tibial plateaus were harvested for biomechanical testing and MRI measurements (Fig.1). ACLT surgical operations were conducted according to the guidelines of the Canadian Council on Animal care and were approved by the Animal Ethic committee at the University of Calgary. Specimens were assessed on a 9.4 T MRI scanner (Oxford instruments Plc, Witney, UK) in combination with a 19-mm quadrature RF volume transceiver (RAPID Biomedical GmbH, Rimpar, Germany). The following parameters were measured using different magnetization preparations followed by a fast spin echo readout (TR/TE_eff=5s/4.3ms, matrix=256x128, slice thickness=1mm and FOV=18x18mm²): (1) T₁ (TI: 200,500,800,1100,1400 and 3000 ms); (2) CWT_1ρ (CW spin-lock pulses (γB₁=1kHz) of 0,4,8,16,32,64 and 128 ms embedded between AHP pulses); (3) AdT_1ρ (trains of 0,4,8,12,24 and 36 adiabatic full-passage (AFP) pulses of 4.5 ms, γB_1,max=2.5kHz); (4) AdT_2ρ (trains of 0,4,8,12 and 24 AFP pulses between adiabatic half-passage (AHP) pulses of 4.5 ms per pulse, γB_1,max=2.5kHz); (5) T₂ (TE = 8.7,12.6,18.2,26.4,38.2,55.3 and 80 ms); (6) T_RAFF (trains of 0,2,4,8 and 16 RAFF pulses of 9 ms length, γB_1,max=625Hz). Maps were calculated for all parameters using MATLAB (Fig.2). The mean values for each parameter were determined for 2-mm wide cartilage ROIs drawn in the load bearing areas of the lateral and medial femur (LF and MF, respectively) and the lateral and medial tibia (LT and MT, respectively) with the articular surface oriented perpendicular with respect to B₀ to minimize the magic angle effect (Fig.1). Additionally, laminar analysis was performed and the mean values for each parameter were determined for the superficial 50% and the deep 50% of the cartilage samples. Differences between groups were tested using Kruskal-Wallis post-hoc tests.

RESULTS

All MRI parameters showed significant elongation in ACLT groups (Tables 1-3), except for T_RAFF. Furthermore, for each parameter, differences were significant at two weeks following surgery in at least one compartment of the knee, consistent with the biomechanical findings: both femoral condyles in ACLT group at two weeks had softer cartilage than controls. Longer T₁, CWT_1ρ, AdT_1ρ, AdT_2ρ and T₂ were found in degenerated cartilage of superficial and bulk ROI in MF and LF as compared to controls (10-130%). Moreover, the 2ACLT group showed significant elongation of AdT_1ρ, AdT_2ρ and T₂ in MT (Table 2). No significant differences were found in LT (data not shown). No significant differences were observed between 2ACLT and 8ACLT groups in any compartment.

DISCUSSION

ACLT in rabbits provides a well-established experimental model for early cartilage degeneration. Previously, elongated values of cartilage CWT_1ρ, AdT_1ρ, AdT_2ρ and T₂ in an ACLT rabbit model have been reported at four weeks post surgery⁴. In the present study, the same quantitative MRI parameters could identify cartilage degeneration as early as two weeks after ACLT. In terms of relative differences in mean values, CWT_1ρ and AdT_2ρ were the most sensitive parameters and changed by 130% and 116% compared to control knees, respectively. AdT_1ρ was the only parameter showing significant elevation in three different compartments within two weeks post surgery. Although the relative differences in mean values were smaller compared to other parameters, longer T₁ values were observed in femur two weeks after ACLT also in the deep cartilage. T_RAFF did not show any significant differences, consistent with a previous study⁴. Differences were mostly significant in the superficial cartilage, consistent with the hypothesis that degeneration starts from the most superficial layers⁵. Regional differences in MRI parameters at different time intervals from ACLT suggest that a multi-parametric approach may provide a more comprehensive assessment of cartilage tissue status at different degrees of degeneration than a single parameter approach.

CONCLUSIONS

MRI parameters can distinguish cartilage changes in an ACLT rabbit model of cartilage degeneration as early as two weeks post surgery and reflect biomechanical findings. Rotating frame parameters showed some evidence of superior sensitivity to cartilage alterations. A multi-parametric approach may enhance the discrimination power of quantitative MRI for osteoarthritis progression.

Acknowledgements

Support from the Academy of Finland (grants #285909 and #293970) and Jane and Aatos Erkko Foundation is gratefully acknowledged.