The association between anterior cruciate ligament (ACL) tears and early osteoarthritis (OA) despite ACL reconstruction (ACLR) is a well-studied phenomenon ^1,3. T_1ρ and T₂ relaxation mapping are noninvasive methods to quantitatively characterize cartilage macromolecular changes in early OA ^2,4. As changes in cartilage composition occur before radiographic evidence is observable, voxel-based relaxometry (VBR) is a novel technique that could provide additional information on localized changes ³. In this study, VBR is used to analyze cartilage of patients with ACL tears at the time of injury and 6 months after ACLR using T_1ρ and T₂ analysis, correlation, and dispersion differences (R₂–R_1ρ) to highlight cartilage changes. This study is the first application of VBR analyzing dispersion differences, a novel method to better assess chemical and diffusive exchange, extending the work of Wang et al., who demonstrated R_1ρ (1/T_1ρ) could characterize cartilage composition more accurately than traditional T_1ρ and T₂ analyses by removing the experimental parameter-dependence of T_1ρ ⁴. Such information can advance the current understanding of chemical exchange in cartilage degeneration.64 patients with no previous history of knee trauma or disease, and sustaining acute, unilateral ACL tears (28 Female; Age=28.7±2.9 years; BMI=24.5±3.1 kg/m2) were scanned using a 3T MR (GE Healthcare). 2 of these patients had previous ACLR in the contralateral knee, and 2 patients did not receive ACLR. Bilateral scans were performed with an 8-channel phased array knee coil (Invivo Inc.) at the time of injury (baseline). 56 patients (24 Female; Age=29.3±12.7 years; BMI=24.7±3.0 kg/m2) were imaged 6 months after ACLR. MRI protocol included quantitative combined T_1ρ/T₂ (T_1ρ TSL= 0/10/40/80 ms, spin-lock frequency=500 Hz, FOV 14 cm, 256×128 matrix, slice thickness 4 mm, T₂ preparation TE=0/12.87/25.69/51.39ms). Non-rigid registration was applied to allineate images onto a template image, allowing VBR to determine relaxation time differences, R₂–R_1ρ dispersion differences and T_1ρ T₂ correlations at the voxel level, obtaining Statistical Parametric Maps (SPM).Significant elevations in T_1ρ and T₂ were observed in the injured knee compared to the contralateral knee at baseline. Elevations were particularly noted in the most posterior aspect of the lateral tibia (LT T_1ρ volume significantly different=39.6%; average p-value in overall compartment=0.01, Fig.1). After 6 months, elevated T_1ρ and T₂ were still observed in the injured knee (LT T_1ρ volume significantly different=47.3%, average p-value in overall compartment=0.01). The analyses of p-value and percent-difference SPMs reveal a more diffuse and anteriorly shifted elevation of T_1ρ and T₂ in the overall pLT at 6 months, no longer focused in the most posterior aspect of pLT as at baseline (Fig.1). Longitudinal comparisons show a significant increase in T_1ρ and T₂ in the trochlea and a decrease in T_1ρ and T₂ in the patella after 6 months. Local correlation analysis between T_1ρ and T₂ is reported in Figure 2. The patella compartment exhibited higher T_1ρ T₂ correlations in the injured side than contralateral at baseline (R=0.91 and R=0.78 respectively, Fig.2A-B), while correlations between injured and contralateral patellar cartilage were more similar at 6 months (R=0.90 and R=0.87, respectively, Fig.2C-D). In dispersion difference analysis, the posterior region of the trochlea remained fairly similar in the injured and uninjured knees at baseline. However, 6-month injured dispersion differences were lower than contralateral (Fig.3). At baseline, the injured patella displayed lower dispersion differences than the contralateral patella. These differences were unobserved at 6 months. A similar trend was observed in the pLT.The trochlea, patella and pLT are three regions demonstrating significant changes after ACL injury. Beyond elevated T_1ρ and T₂ in baseline injured pLT, dispersion difference analysis suggests T_1ρ and T₂ values are more similar at 6 months than baseline, which may suggest a partial recovery following reconstruction. Future experiments can further elaborate on dispersion difference analysis with various TSLs, isolating the pH-dependent factor, as demonstrated in the simplified Chopra model ^4,5: $$$R_{1\rho}=R_2+p_{ex}{\large[}R_{2ex}+\frac{{k_{ex}\Delta w_0^2}}{k_{ex}^2+\Delta w_0^2+w_1^2}\large]$$$. Similar findings in patellar cartilage from relaxation time analysis and dispersion differences reinforce this observed reversible degeneration seen in pLT. Reduction in correlation between T_1ρ and T₂ in the injured patella at 6 months compared to baseline indicates greater similarity between injured and uninjured knee relaxation times after 6 months, which may be due to surgical restoration of normal tibiae translation (Fig.2). The trochlea shows greater relaxation times at 6 months than baseline, indicating cartilage degeneration 6 months post-reconstruction. Dispersion differences echo this finding between injured and contralateral knees at 6 months, compared to similar values at baseline (Fig.3). Findings from this study emphasize the need for local and multi-parametric approaches for more sensitive analyses of early degeneration after injury.