Objective To describe cartilage matrix and morphology changes, assessed using quantitative MRI, after acute anterior cruciate ligament (ACL) injury relative to controls and longitudinally during 2 years following reconstruction. Method Fifteen patients with acute ACL injuries and sixteen healthy volunteers with a similar demographic profile but no history of osteoarthritis or knee injury were studied. The injured knee of each participant was imaged with a 3.0 T MR scanner at baseline (prior to ACL reconstruction); patients’ knees were re-imaged 1- and 2-years after ACL reconstruction. Cartilage T1ρ and T2 values in full thickness, superficial layers, and deep layers, and cartilage thickness of the full layer were quantified within subcompartments of the knee joint. Results In the posterolateraltibial cartilage, T1ρ values were significantly higher in ACL-injured knees than control knees at baseline and were not fully recovered at the 2-year after ACL reconstruction. T1ρ values of medial tibiofemoral cartilage in ACL-injured knees increased over the 2-year study and were significantly elevated compared to that of the control knees. T2 values in cartilage of the central aspect of the medial femoral condyle at the 2-year follow-up were significantly elevated compared with control knees. Cartilage in the posterior regions of the lateral tibia was significantly thinner, while cartilage in the central aspect of the medial femur was significantly thicker than that of controls. Patients with lesions in the posterior horn of the medial meniscus exhibited significantly higher T1ρ values in weight-bearing regions of the tibiofemoral cartilage than that of control subjects over the two year period, whereas patients without medial meniscal tears did not. Conclusion Quantitative MRI provides powerful in vivo tools to quantitatively evaluate early changes of cartilage matrix and morphology after acute ACL injury and reconstruction, which may possibly relate to the development of post-traumatic osteoarthritis in such joints.

OBJECTIVE To evaluate the longitudinal reproducibility and variations of cartilage T1ρ and T2 measurements using different coils, MR systems and sites. METHODS Single-Site study: Phantom data were collected monthly for up to 29 months on four GE 3T MR systems. Data from phantoms and human subjects were collected on two MR systems using the same model of coil; and were collected on one MR system using two models of coils. Multi-site study: Three participating sites used the same model of MR systems and coils, and identical imaging protocols. Phantom data were collected monthly. Human subjects were scanned and rescanned on the same day at each site. Two traveling human subjects were scanned at all three sites. RESULTS Single-Site Study: The phantom longitudinal RMS-CVs ranged from 1.8% to 2.7% for T1ρ and 1.8% to 2.8% for T2. Significant differences were found in T1ρ and T2 values using different MR systems and coils. Multi-Site Study: The phantom longitudinal RMS-CVs ranged from 1.3% to 2.6% for T1ρ and 1.2% to 2.7% for T2. Across three sites (n=16), the in-vivo scan-rescan RMS-CV was 3.1% and 4.0% for T1ρ and T2, respectively. Phantom T1ρ and T2 values were significantly different between three sites but highly correlated (R>0.99). No significant difference was found in T1ρ and T2 values of traveling controls, with cross-site RMS-CV as 4.9% and 4.4% for T1ρ and T2, respectively. CONCLUSION With careful quality control and cross-calibration, quantitative MRI can be readily applied in multi-site studies and clinical trials for evaluating cartilage degeneration.

Objective To determine if cartilage T1ρ and T2 relaxation time measures after ACL injury and prior to reconstruction (baseline) are associated with patient-reported outcomes at baseline, 6-months, and 1-year after surgery. Design Fifty-four ACL-injured participants were scanned in both knees at baseline using 3T MR T1ρ and T2 mapping. Participants also completed Knee-injury and Osteoarthritis Outcome Score (KOOS) and Marx activity level questionnaires at baseline, 6-months, and 1-year after reconstruction. The difference between cartilage T1ρ or T2 of the injured and contralateral knee (side-to-side difference, SSD) was calculated to account for physiological variations among patients. Linear regression models were built to evaluate the association between the baseline SSD T1ρ or T2 and KOOS or Marx at all time points. Results Higher baseline SSD T1ρ posterolateral tibia (pLT) was associated with worse KOOS in all subscales except symptoms at baseline, worse KOOS pain at 6-months, and worse KOOS in all subscales except sports function at 1-year. Higher baseline SSD T2 femoral trochlea was associated with worse KOOS activities of daily living at 1-year. Higher baseline SSD T1ρ pLT was associated with lower Marx activity level at 1-year. More severe cartilage lesions, as assessed by Whole-Organ MRI Scoring (WORMS), was significantly associated with worse KOOS pain at 6-months and 1-year. Conclusion T1ρ and T2 of cartilage after ACL injury were associated with KOOS after injury and both KOOS and Marx after reconstruction. Such associations may help clinicians stratify outcomes post-injury, and thus, improve patient management.

Objective: To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1r and T2 relaxation time measurements. Design: 26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1r and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data. Results: The degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-g (r partial ¼ 0.64, 95% CI (0.26e0.85)), IL-10 (r partial ¼ 0.47, 95% CI (0.04e0.75)), IL-6 (r partial ¼ 0.56, 95% CI (0.16e0.81)), IL-8 (r partial ¼ 0.49, 95% CI (0.06e0.76)), TNF-a (r partial ¼ 0.55, 95% CI (0.14e0.80)) and of the chondrodestructive markers MMP-1 and-3 (MMP-1: r partial ¼ 0.57, 95% CI (0.17 e0.81); MMP-3: r partial ¼ 0.60, 95% CI (0.21e0.83)). IPFP abnormalities were significantly associated with higher T1r and T2 values in the trochlear cartilage (T1r: r partial ¼ 0.55, 95% CI (0.15e0.80); T2: r partial ¼ 0.58, 95% CI (0.18e0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 r partial 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (r partial ¼ 0.57, 95% CI (0.17e0.81)). Conclusions: This exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.

Purpose: (1) To identify bone-shape changes from baseline to 3-years after anterior cruciate ligament reconstruction (ACLR). (2) to assess association between changes in bone-shape from baseline to 6-months and changes in cartilage matrix and patient functions and symptoms from baseline to 3-years after ACLR. Methods: Bilateral knees of 30 patients with unilateral ACL injuries were scanned at baseline, 6-months, 1-, 2-, and 3-years after ACLR. Bilateral knees of 13 controls were scanned at baseline, 1-and 3-years. Mean T1r and T2 values of each cartilage compartment were computed. Bone shape was quantified using statistical shape modeling (SSM) and 3D-MRI. Patient functions and symptoms were evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS). Results: Statistically significant changes were observed in Femur 2 (medial femoral condyle [MF] shape), Femur 6 (intercondylar notch width), Tibia 1 (tibia plateau area), and Tibia 7 (medial tibia slope) over 3-years after ACLR. Statistically significant differences were observed between injured and control knees in several modes. Statistically significant correlations were found between changes in bone shape (DFemur 6, DFemur 8 [trochlea inclination and MF height], DTibia 1) from baseline to 6-months and that of cartilage T1r and T2 and KOOS from baseline to 3-years after ACLR. Conclusion: Bone shape remodeling occurs after ACLR, and early bone shape changes (within 6 months) correlated with cartilage matrix and patient outcomes at 3-years after ACLR. Bone shape can be a promising imaging biomarker that stratifies patients at high risk for post-traumatic osteoarthritis (PTOA).

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Purpose: Osteoarthritis (OA) is one of the leading causes of long-term pain and disabilities associated with musculoskeletal disorders. Effective treatment and disease-progression slowdown depend on early detection and quantification of risk. However, current disease parameters, like joint space width (JSW), have proven to be insufficient for the prediction of OA. The purpose of the present study was to investigate if combining fractal-and entropy-based bone texture analyses with joint space width (JSW) and joint space area (JSA) may improve prediction of OA. Methods: Conventional posterior-anterior (PA) knee radiographs of men and women were obtained from the Multicenter Osteoarthritis Study (MOST) database. Oriented fractal-and entropy based texture algorithms were developed, using state-of-the-art computer hardware and software as well as specific machinelearning algorithms. The selected subchondral area used for textural analyses included 4 regions of interest (ROI) in the proximal tibia and one on each condyle of the distal femur (Fig. 1). Furthermore, JSW and JSA were assessed using newly developed and fully automated software. Results: 1092 conventional knee radiographs obtained from one study center were screened for eligibility. Of these, a total of 574 radiographs (230 women, 344 men) met the inclusion criteria, i.e. a Kellgren & Lawrence (KL) score of 0 at baseline. At month 84, 41 female and 79 male patients had developed KL!1, and 189 female and 265 male patients remained at KL0. Area-Under-the-Curve (AUC) for incident OA using JSW/JSA and clinical features was 0.67±0.08 for women, and 0.61±0.1 for men. In contrast, combining fractal/entropybased texture, JSW/A and clinical features resulted in significantly improved AUC for women and men (0.80±0.07 for women and 0.69±0.1 for men, respectively). To test whether these differences in predicting incident-OA were significant, we performed classifier comparison: t ¼ 3.84; p < 10-3 for women, and t ¼ 3.38; p < 10-3 for men. Conclusions: This study provides strong evidence, that a combination of fractal-and entropy-based textural analyses of plain subchondral bone radiographs together with JSW/A and clinical features is superior to JSW/A and clinical features alone in predicting incident OA in men and women.