BACKGROUND:People suffering anterior cruciate ligament (ACL) injuries are at increased risk for development of osteoarthritis (OA). This study investigated associations between daily step count, cartilage degeneration and patient-reported outcomes 2 years after ACL reconstruction (ACLR). HYPOTHESIS:Daily step count is associated with cartilage health and patient-reported knee symptoms and function 2 years after ACLR. STUDY DESIGN:Cross-sectional. LEVEL OF EVIDENCE:Level 4. METHODS:We analyzed data from 34 patients (18 female), aged 33.4 ± 10.8 years with stable knees recruited from the community 2 years after primary ACLR. Mean daily step count was measured using an activity tracker (FitBit) over a 7-day collection period. Cartilage morphology on magnetic resonance imaging (MRI) was graded across multiple joint areas. Knee symptoms and function were assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales pain, symptoms, activity of daily living (ADL), sport/recreation (sport/rec), and knee-related quality of life (QoL) using published thresholds for patient acceptable symptom state (PASS). Analyses were adjusted for age, sex, and body mass index. RESULTS:The mean (SD) daily step count was 9276 (3199). At least 1 cartilage abnormality was present on morphological MRI in 20% of ACLR knees. The mean (SD) KOOS values were: pain 94 (7), symptoms 92 (8), ADL 91 (10), function in sport/rec 85 (14), and knee-related QoL 56 (22). Failure to achieve PASS rates were 76% for ADL; 59% for QoL, 18% for pain, 35% for sport/rec, and 0% for symptoms. CONCLUSION:Daily step count was not associated with cartilage health or knee symptoms and function 2 years after ACLR. However, a high proportion of participants with reported unacceptable ADL and QoL 2 years after ACLR. CLINICAL RELEVANCE:The proportion with unacceptable PASS for ADL and QoL in participants with stable knees after ACLR indicates a need to optimize rehabilitation and improve post-ACLR recovery.

Clinical outcomes vary after anterior cruciate ligament reconstruction (ACLR), and osteoarthritis (OA) risk remains high. Consequently, early identification is needed of patients who show potentially modifiable loading patterns suggestive of higher risk for worse outcomes and pre-OA. This study tested the hypothesis that (1) Patient Acceptable Symptom State (PASS) status derived from the Knee injury and Osteoarthritis Outcome Score (KOOS) is associated with knee loading patterns 2 years after ACLR and (2) failure to achieve the PASS reflects worse knee loading mechanics. Cross-sectional study; Level of evidence, 4. Fifty-nine participants with unilateral ACLR (mean ± SD, 33 ± 10 years; 33 [56%] females) assessed by gait analysis and KOOS at 2-year follow-up were categorized according to published KOOS PASS thresholds. Independent t tests compared knee flexion moment (KFM), knee adduction moment (KAM), and their relative percentage contributions to total joint moment between PASS statuses. Associations between loading metrics and PASS were examined using mixed effects logistic regression. Although PASS rates for KOOS subscales ranged from 42% to 100%, only 36% of participants achieved the PASS on all 5 KOOS subscales. Patients achieving the PASS on a given KOOS subscale exhibited different loading patterns when compared with those who did not (PASS-no). Specifically, PASS-no for pain and knee-related quality of life showed lower KFM (P ≤ .024), and PASS-no for activities of daily living showed higher KAM (P = .009). Lower KFM and higher KAM were associated with lower likelihood of achieving the PASS on the KOOS subscales (P ≤ .035). A shift from KFM dominance to KAM dominance in PASS-no, as suggested by lower percentage KFM (P ≤ .026) and higher percentage KAM (P ≤ .047) to total joint moment, was consistent across the KOOS subscales for pain, knee related quality of life, and function in activities of daily living. Additionally, failure to achieve the PASS on some KOOS subscales was associated with more varus alignments (P ≤ .043), earlier ACLR (P = .006), and lower Tegner activity levels (P = .043). Nearly two-thirds of ACLR recipients failed to achieve the PASS on all KOOS subscales 2 years after ACLR. Failure to achieve the PASS was associated with knee loading patterns linked to worse longer-term outcomes and greater OA risk. The KOOS PASS criterion is an accessible screening tool for identifying patients in need of further assessment and treatment to improve knee health and reduce OA risk after ACLR.

INTRODUCTION Quantitative MRI and [¹⁸F]NaF PET enable assessment of cartilage composition, bone shape, and subchondral bone metabolism in knee OA. Current workflows rely on manual segmentation that is time-consuming and subject to inter- and intra-reader variability. Furthermore, computing quantitative metrics requires considerable time and expertise. An open-source, automated, deep learning (DL) pipeline with standardized biomarker extraction has the potential to enhance reproducibility and make large-scale analysis accessible to clinical research communities, including non-technical users. OBJECTIVE Develop and validate an automated DL-based pipeline for comprehensive MRI-based segmentation and quantitative analysis of multiple knee tissues from multi-modal MR and PET images. METHODS We developed and open-sourced a comprehensive segmentation and analysis pipeline. A 2D U-Net was trained to segment 9 tissues using a dataset of 347 DESS and qDESS images: 3 bones (femur, tibia, patella), 4 cartilage regions (femoral, medial and lateral tibial, patellar), and 2 menisci (medial and lateral). Subchondral bone masks and femoral cartilage subregions were fitted automatically. Quantitative imaging biomarkers were computed as follows: cartilage T2 was computed analytically from qDESS scans; cartilage thickness was computed as the 3D Euclidean thickness of cartilage overlying the bone surface; meniscal volume was calculated as the product of voxel count and voxel volume; OA bone shape (BScore) was derived using a neural shape model; PET-derived subchondral bone metabolism was computed as regional SUVmean/max, and kinetic modeling via Hawkin’s method was used to extract KiNLR (bone mineralization rate) and K1 (perfusion to subchondral bone). To evaluate the pipeline, 20 unilateral qDESS and [¹⁸F]NaF PET knee scans (10 symptomatic OA, 10 controls) were analyzed by the automated pipeline, and two manual annotators. Manual and automated segmentations were compared using the Dice Similarity Coefficient (DSC) and average symmetric surface distance (ASSD). Biomarkers were compared using ICC and normalized mean RMSE (NRMSE). RESULTS All automated segmentations had good to excellent overlap measured using DSC (bone: 0.95-0.98; cartilage: 0.84-0.91; menisci: 0.85-0.89) and small surface errors (bone: 0.13-0.32 mm; cartilage: 0.11-0.21 mm; menisci: 0.17-0.30 mm). Notably, automated segmentations had better DSC and ASSD than the inter-rater comparison (Fig. 2). With the exception of cartilage thickness and patellar cartilage whole T2 values, all quantitative metrics showed excellent agreement with ICC >0.96 and NRMSE <0.1, comparable to inter-rater comparison. Bone metrics (BScore, SUV, PET kinetics) had ICC >0.96. Cartilage metrics had more variability, with the best reproducibility for whole cartilage T2 (ICC 0.89-0.98, NRMSE 0.01-0.04), then superficial T2 (ICC 0.93-0.99, NRMSE 0.01-0.05), and finally deep T2 (ICC 0.7-0.97, NRMSE 0.01-0.06). Cartilage thickness showed the worst reproducibility but still was comparable to inter-rater measures. Meniscus volume also shows high concordance (ICC 0.93-0.97; NRMSE 0.05-0.10). Overall, we found that most of the metrics derived from automated segmentations are comparable to those derived from manual segmentations. CONCLUSION Our open-source, AI-driven pipeline delivers rapid, accurate segmentation and quantitative analysis of multimodal knee MRI and PET data. Next steps include support for other MR sequences, multi-site validation, and 3D Slicer integration to facilitate translation. This resource provides a foundation for reproducible and scalable imaging biomarker analysis in OA research and clinical trials.

Purpose (the aim of the study): Planus foot morphology ("flat-footedness") and pronated ankle posture have been observed in patients with knee osteoarthritis (OA). Previous magnetic resonance imaging (MRI) detection of gross medial tibiofemoral (TF) cartilage damage, including at least partial-thickness defects, were shown to associate with flat-footedness in older adults. The question arises whether more subtle compositional changes to cartilage, assessed from T2 relaxation times in participants without clinical OA, are likewise associated with foot and ankle posture. This study tests the hypotheses that medial foot center of pressure (COP), ankle eversion, and tibial rotation associate with tibiofemoral cartilage T2.

Objectives: Anterior cruciate ligament (ACL) tears are common knee injuries that greatly increase osteoarthritis (OA) risk. By 1 year after ACL reconstruction (ACLR), most patients have been released to unrestricted activities. However, ACLR does not fully restore knee mechanics and altered knee loading has been associated with greater OA risk. Knee mechanics can be challenging to measure. Consequently, clinical outcomes are more commonly assessed using patient reported outcomes (PRO) such as the Knee Injury and Osteoarthritis Outcome Score (KOOS). Patient acceptable symptom state (PASS) criteria were developed to aid in the interpretation of the KOOS. This study was performed to test the following hypotheses: (1) that loading patterns of ACLR knees 2 years after ACLR differ between patients who achieve an acceptable symptom state (PASS-Y) and those who do not (PASS-N); and (2) that those who fail to reach PASS exhibit loading patterns associated with greater pain and higher OA risk. Methods: This IRB-approved study included 59 individuals who completed the KOOS and underwent gait analysis 2 years after primary unilateral ACLR (Table 1). The gait test acquired three walking trials at a self-selected comfortable pace using a standard 3D motion capture system (Qualisys & Bertec synchronized at 120 Hz) with the point cluster technique. External knee moments relative to the tibial frame were calculated using an inverse dynamic approach and normalized to percent body weight multiplied by height (%BW×Ht). The total joint moment (TJM) was calculated for each time point of the stance phase as the Euclidean norm of the flexion (KFM), adduction (KAM), and rotation (KRM) moments. Absolute loading metrics, peak KFM, KAM, KRM, and TJM, were extracted from early stance. Relative loading metrics were the %KFM, %KAM, and %KRM contribution to peak TJM. Participants were dichotomized based on ACLR-specific KOOS PASS-Y criteria: 88.9 (pain), 57.1 (symptoms), 100 (function in activities of daily living, ADL), 75 (function in sports and recreation, sport/rec), 62.5 (knee-related quality of life, QoL). Participant factors, surgical factors, and loading metrics between PASS-Y and PASS-N were compared using independent t-tests (or Mann-Whitney U tests if non-normally distributed; Fisher’s exact test for categorical variables). Relationships between the loading metrics and PASS were examined with mixed effects logistic regression and odds ratios were computed. Results are reported as mean (95% confidence interval (CI)). Results: While all participants (59/59) met PASS-Y for symptoms, only 36% (21/59) achieved PASS in all domains (Figure 1). Those meeting PASS-Y were sports/rec=43 (73%), QoL=39 (66%), pain=39 (66%), and ADL=25 (42%). Participant & Surgical Factors: Those with PASS-N for pain and ADL showed a more varus mechanical axis (-1.0 [-2.1, 0.2]°, p = 0.043; -1.3 [-2.3, -0.3]°, p = 0.014, respectively). PASS-N for ADL also showed a lower Tegner score than PASS-Y (-1.1 [-2.0, -0.0], p = 0.043). No differences in graft type or meniscus status were observed. Loading Metrics: Those with PASS-N for pain and QoL showed a lower KFM (-0.85 [-1.49, -0.22] % BW×Ht, p = 0.016; -0.75 [-0.14, -0.10] % BW×Ht, p = 0.024 respectively). Those with PASS-N for ADL had higher KAM (0.42 [0.11, 0.74] % BW×Ht, p = 0.009). No differences were observed between PASS-Y and PASS-N for KRM and TJM. Across the KOOS pain, ADL, sport/rec, and QoL subscales, PASS-N consistently demonstrated a lower %KFM and a higher %KAM compared to PASS-Y (Figure 2). Loading vs. PASS: Participants with a lower KFM had odds of 1.94 [1.11, 3.40] (p = 0.020) and 1.75 [1.04, 2.96] (p = 0.035) for not attaining PASS in pain and QoL, respectively. Participants with a higher KAM had odds of 3.53 [1.29, 9.61] (p = 0.014) for not attaining PASS in ADL. These results still applied with the addition of independent explanatory variables (i.e., mechanical axis for KFM vs. pain; Tegner for KAM vs. ADL). Conclusions: Nearly two-thirds of patients 2 years after ACLR did not achieve PASS in at least one KOOS subscore. Failure to achieve PASS correlated with quantitative gait data reflecting altered loading known to reduce longer term outcomes. These data demonstrated utility and sensitivity of the KOOS subscore PASS criteria for personalized assessment of outcomes early after ACLR where the relative lack of symptoms may mask suboptimal recovery. Furthermore, participants 2 years after ACLR who did not consistently reach PASS exhibited loading patterns associated with greater pain and greater OA risk than those achieving PASS-Y. Cross-sectionally greater KAM 2 years post-ACLR has been shown to correlate with medial knee degenerative changes at the same time point and to predict worse outcomes 8 years after ACLR. ACLR knees with a lower KFM than contralateral knees also exhibited altered extensor/flexor co-activation patterns. The KFM and TJM are responsive to changes in pain and are indicative of knee muscle strength and activation. This means that interventions aimed to increase KFM and to restore the relative loading contributions (%KFM & %KAM) to TJM may lead to improved quadriceps strength and pain relief. The absolute loading metrics, as suggested by the regression analyses, may also have predictive value for identifying participants who may benefit from additional interventions. Significance: These data suggest that KOOS PASS criteria may be an accessible screening tool to provide early warning of patients at higher risk for poor outcomes who may potentially benefit from further assessment, additional physical therapy, or closer follow-up.

Purpose (the aim of the study): Platelet-rich plasma (PRP) presents as an appealing osteoarthritis (OA) treatment, but evidence supporting its effectiveness remains mixed. Previous studies assessed PRP efficacy using patient-reported outcomes (PROs) and MRI structural measures, with few studies using gait analysis. Gait measures, which showed sensitivity to experimental pain induction, short-term pain relief, and longer-term cartilage health, may provide additional insights into individuals' responses to PRP.

Background Cartilage T 2 can detect joints at risk of developing osteoarthritis. The quantitative double‐echo steady state (qDESS) sequence is attractive for knee cartilage T 2 mapping because of its acquisition time of under 5 minutes. Understanding the reproducibility errors associated with qDESS T 2 is essential to profiling the technical performance of this biomarker. Purpose To examine the combined acquisition and segmentation reproducibility of knee cartilage qDESS T 2 using two different regional analysis schemes: 1) manual segmentation of subregions loaded during common activities and 2) automatic subregional segmentation. Study Type Prospective. Subjects 11 uninjured participants (age: 28 ± 3 years; 8 (73%) female). Field Strength/Sequence 3‐T, qDESS. Assessment Test–retest T 2 maps were acquired twice on the same day and with a 1‐week interval between scans. For each acquisition, average cartilage T 2 was calculated in four manually segmented regions encompassing tibiofemoral contact areas during common activities and 12 automatically segmented regions from the deep‐learning open‐source framework for musculoskeletal MRI analysis (DOSMA) encompassing medial and lateral anterior, central, and posterior tibiofemoral regions. Test–retest T 2 values from matching regions were used to evaluate reproducibility. Statistical Tests Coefficients of variation (%CV), root‐mean‐square‐average‐CV (%RMSA‐CV), and intraclass correlation coefficients (ICCs) assessed test–retest T 2 reproducibility. The median of test–retest standard deviations was used for T 2 precision. Bland–Altman (BA) analyses examined test–retest biases. The smallest detectable difference (SDD) was defined as the BA limit of agreement of largest magnitude. Significance was accepted for P < 0.05. Results All cartilage regions across both segmentation schemes demonstrated intraday and interday qDESS T 2 CVs and RMSA‐CVs of ≤5%. T 2 ICC values >0.75 were observed in the majority of regions but were more variable in interday tibial comparisons. Test–retest T 2 precision was <1.3 msec. The T 2 SDD was 3.8 msec. Data Conclusion Excellent CV and RMSA‐CV reproducibility may suggest that qDESS T 2 increases or decreases >5% (3.8 msec) could represent changes to cartilage composition. Level of Evidence 2. Technical Efficacy Stage 2.

Purpose (the aim of the study): Autologous platelet rich plasma (PRP) injections are increasingly used to treat painful knee osteoarthritis (OA). PRP therapy is postulated to have anti-inflammatory and regenerative effects, however, individual responses to PRP treatment vary widely and clinical evidence of potential benefits to cartilage structure remain lacking. Our aim was to study osteoarthritis symptoms and articular cartilage structure assessed before and 6 months after completion of PRP treatment for painful knee OA using patient reported outcomes and T2 and UTE-T2* relaxation times, quantitative magnetic resonance imaging (qMRI) parameters sensitive to cartilage matrix composition and organization.

Objectives: Patellofemoral (PF) knee pain affects 20-30% of the general population. There is growing evidence that chronic PF pain is associated with the development of osteoarthritis (OA). Among the many biomechanical factors contributing to PF pain and pathology, flat-footedness and ankle eversion may be accessible targets for therapeutic interventions. These factors influence the patellofemoral joint by coupling with the tibia, where subtalar joint pronation causes internal tibial rotation, pulling the patellar tendon medially to alter alignment and tracking of the patella. Subtle degenerative changes in cartilage can be detected with MRI compositional measures such as T2 and T1ρ. In patellar lateral facets of patients with PF pain but no evidence of OA, elevated cartilage T1ρ has previously been reported. The goal of this study is to investigate the relationships between PF joint cartilage composition and biomechanical foot and ankle measures thought to impact PF health. This study tests the hypotheses that more medial foot center of pressure (COP), greater ankle eversion, and greater internal tibial rotation associate with greater patellar or trochlear cartilage T2 values. Methods: Participants provided written consent to participate in this IRB-approved study. The study cohort consisted of 23 participants with knee MRI, lower limb radiographs and gait assessments acquired 2 years after unilateral ACL reconstruction (ACLR), Table 1. MRI, x-ray, COP and gait data from only the uninjured limbs of the study cohort were assessed. PF cartilage in these participants was grossly intact on morphological MRI. A 10-camera optoelectronic system (Qualisys) and force plate (Bertec) were used to measure participants’ motion. Average ankle eversion over stance (°) and external tibial rotation (°) were calculated from 3 walking trials at normal self-selected speed. Foot center of pressure (COP, cm) relative to the midfoot axis was measured from the force plate. Frontal-plane mechanical axis was determined from full-length standing-alignment radiographs of the lower limbs. Knee MRIs were acquired on a 3T scanner (GE, Healthcare). T2 maps were generated from a quantitative double-echo in steady state (qDESS) MRI sequence (TR/TEs 21 ms/6, 36 ms; 0.417 x 0.417 mm resolution; 1.5 mm slice thickness). T2 values in full-thickness articular cartilage were determined in 2 “tread mark” regions on patellar and trochlear surfaces (largely consistent with known regions of cartilage contact during common daily activities), by manually segmenting 7 contiguous central qDESS slices (10.5 mm wide right to left) with custom software (MATLAB, TheMathWorks), Figure 1. Statistics: Correlations between 4 potentially independent factors (COP, ankle eversion, tibial rotation and mechanical axis) and cartilage T2 were assessed with Pearson correlations. Adjusted p<0.013 was accepted as significant. Linear regression assessed effects of age, sex and BMI on the correlations. Statistical analyses were performed with SPSS (IBM) and GraphPad (Dotmatrics). Results: Correlations of COP, kinematics and mechanical axis to knee cartilage T2: More medial foot COP correlated to lower trochlear cartilage T2 values (R=-0.52, p=0.011), Figure 2. Greater average ankle eversion showed trends for association with lower trochlear cartilage T2 (R= -0.43, p=0.040) and lower patellar cartilage T2 (R=-0.35, p=0.102). There was a trend for association between more valgus mechanical axis and higher trochlear cartilage T2 (R=0.42, p=0.059). No correlations were detected for tibial rotation and either trochlear or patellar cartilage T2 ( p> 0.59). Linear regression found no effects on these results by age, sex, or BMI. Among biomechanical factors, more medial COP correlated to greater average ankle eversion (R=0.61, p=0.002) and showed a trend for association with greater internal tibial rotation (R=-0.36, p=0.093). No other correlations were detected between foot COP, average ankle eversion, tibial rotation or mechanical axis. Conclusions: The results of this study suggest that in knees without clinical evidence of osteoarthritis, biomechanical measures of the ipsilateral foot and ankle are related to patellofemoral cartilage composition. Specifically, more medial COP and greater ankle eversion showed a correlation and trends, respectively, for lower cartilage MRI T2. While the directions of these associations are opposite to our hypothesis, they are in-line with previous studies showing T2 decreases with early subsurface compositional degeneration in morphologically surface-intact cartilage. These results are also in general agreement with studies that found excessive external tibial rotation correlated to greater patellar cartilage UTE-T2* and more laterally directed foot pressure during walking associated with anterior knee pain. In other prior work, although medial patellar cartilage damage diagnosed from morphologic MRI was detected in nearly 60% of older adults, no association was found between planus foot morphology and PF cartilage damage. By contrast, relationships between PF cartilage and foot and ankle biomechanics measured here may reflect a greater sensitivity of compositional T2 mapping compared to morphologic MR imaging to subtle and early structural changes within cartilage. In conclusion, though many biomechanical factors contribute to PF pain, foot and ankle alignment may also deserve consideration during screening and assessment for possible intervention. Correlation of foot COP to cartilage composition at the knee raises the intriguing possibility that strategies involving gait retraining or shoe interventions to alter weight distribution at the foot and ankle could be utilized to benefit to knee cartilage health to prevent or delay osteoarthritis.

Purpose: Anterior cruciate ligament (ACL) tears are often accompanied by trauma to the posterior medial meniscus (pMM), the secondary restraint to anterior tibial translation. Magnetic resonance imaging (MRI) ultrashort echo time-enhanced T2* (UTE-T2* mapping) is sensitive to subsurface injury and degeneration of the pMM following ACL tear, even in the absence of frank meniscal tear or other clinically detectable meniscus pathologies. However, the degree to which compositional changes of the pMM are associated with patient reported outcomes (PROs) in the mid-term following ACLR has not been examined.

This work evaluates mono- and bi-exponential UTE-T2* relaxation in 6 tread mark regions of knee cartilage of 18 participants with ACL-injury prior to reconstruction surgery and in 15/18 participants 2 years after surgery. Bi-exponential T2* short had a smaller fractional contribution than T2* long in all regions examined. However, T2* short accounted for a higher fraction of total signal in deep cartilage layers compared to superficial. While both mono- and bi-exponential UTE-T2* analyses showed significant longitudinal changes, bi-exponential analyses did not exceed the sensitivity of mono-exponential UTE-T2* for detection of knee cartilage compositional changes over the first two years following ACL reconstruction.

Background: Anterior cruciate ligament (ACL) injury increases risks for osteoarthritis (OA), a poorly modifiable and disabling condition. Joint changes of potentially reversible pre-OA have been described just 2 years after ACL reconstruction (ACLR) when early bone shape changes have also been reported. Purpose: This study evaluates relationships between interlimb differences in tibiofemoral bone shape derived from statistical shape modeling (SSM) of magnetic resonance imaging (MRI) and participant factors on patient-reported outcomes 2 years after unilateral ACLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: SSM-derived tibiofemoral bone shape and subchondral bone area were assessed from bilateral knee MRI scans of 72 participants with unilateral ACLR (mean age, 34 ± 11 years; 32 women) and compared with a reference cohort of 398 older individuals without OA (mean age, 50 ± 3 years; 213 women). Multivariable logistic regression models examined relationships between participant and surgical factors with interlimb differences in bone shapes or subchondral bone areas. Relationships between patient-reported outcomes and the interlimb differences in bone shape and subchondral area were examined using similar models. Results: Bone shape scores and subchondral bone areas were greater (more OA-like) in ACLR knees than uninjured contralateral knees in every bone metric tested ( P≤ .001). Interlimb differences in femur shape scores of participants with ACLR were 65% greater ( P < .001) than those of the significantly older reference cohort. Taller height, medial meniscal tears, and decreasing age were associated with larger interlimb differences in shape scores and subchondral areas ( P < .05). Bone–patellar tendon–bone (BPTB) autograft recipients demonstrated greater interlimb subchondral area differences compared with allograft recipients ( P < .05). Interlimb differences for hamstring autograft recipients did not differ from those with BPTB or allograft. Greater interlimb differences in medial femur subchondral areas were associated with worse patient-reported Knee injury and Osteoarthritis Outcome Score Symptoms ( R = 0.27; P = .040). Conclusion: Even in the absence of radiographic OA, just 2 years after unilateral ACLR patients showed greater bone shape scores and subchondral areas consistent with pre-OA in their ACLR knees. Furthermore, greater medial femur bone areas were weakly associated with worse symptoms. Patients who are younger, are taller, have meniscal tears, or have BPTB grafts may be at increased risk for bony asymmetries 2 years after ACLR.

Osteoarthritis (OA) is a leading cause of pain and disability for which disease-modifying treatments remain lacking. This is because the symptoms and radiographic changes of OA occur after the onset of likely irreversible changes. Defining and treating earlier disease states are therefore needed to delay or to halt OA progression. Taking this concept a step further, studying OA pathogenesis before disease onset by characterizing potentially reversible markers of increased OA risk to identify a state of "pre-osteoarthritis (pre-OA)" shifts the paradigm towards OA prevention. The purpose of this review is to summarize the 42 studies comprising the 2019 Kappa Delta Elizabeth Lanier Award where conceptualization of a systems-based definition for "pre-osteoarthritis (pre-OA)" was followed by demonstration of potentially reversible markers of heightened OA risk in patients after anterior cruciate ligament (ACL) injury and reconstruction. In the process, these efforts contributed a new magnetic resonance imaging method of ultrashort echo time (UTE) enhanced T2* mapping to visualize joint tissue damage before the development of irreversible changes. The studies presented here support a transformative approach to OA that accounts for interactions between mechanical, biological, and structural markers of OA risk to develop and evaluate new treatment strategies that can delay or prevent the onset of clinical disease. This body of work was inspired by and performed for patients. Shifting the paradigm from attempting to modify symptomatic radiographic OA towards monitoring and reversing markers of "pre-OA" opens the door for transforming the clinical approach to OA from palliation to prevention.

Objective Anterior cruciate ligament reconstruction (ACLR) has not been shown to decrease the risk for development of post-traumatic osteoarthritis. Magnetic resonance imaging (MRI) T2 mapping can be used to assess cartilage compositional changes. This study tests whether (1) worse cartilage arthroscopic status at ACLR is reflected by higher cartilage T2 values in matched study regions 6 weeks and 1 year after ACLR, and (2) increasing cartilage T2 values between 6 weeks and 1 year after ACLR are associated with worsening patient-reported outcomes. Design Twenty-two participants with ACLR and 26 controls underwent 3T MRI. T2 values in medial and lateral femoral and tibial cartilage were measured at 6 weeks and 1 year after ACLR and compared with arthroscopic grades, Knee injury and Osteoarthritis Outcome Scores (KOOS), and control T2 values. Results Most (59%-86%) cartilage study regions examined by arthroscopy demonstrated intact articular surfaces. Average T2 value increased in 3 of 4 study regions between 6 weeks and 1 year after ACLR (P = .001-.011). T2 value increased (P < .013) even for participants whose cartilage had intact articular surfaces at ACLR. Participants with ACLR who showed greater increases in cartilage T2 values had less improvement to KOOS Quality of Life (P = .009, ρ = −0.62). Discussion Cartilage status assessed arthroscopically at ACLR and by MRI T2 maps 6 weeks later was healthier than cartilage status assessed by MRI T2 maps at 1-year follow-up. Progressive T2 elevations were observed over the first year after ACLR even in patients with arthroscopically intact cartilage at the time of surgery and were associated with reduced improvement in knee quality of life suggesting preosteoarthritis.

Background: Patellofemoral joint degeneration and dysfunction after anterior cruciate ligament reconstruction (ACLR) are increasingly recognized as contributors to poor clinical outcomes. Purpose: To determine if greater deep cartilage matrix disruption at 2 years after ACLR, as assessed by elevated patellofemoral magnetic resonance imaging (MRI) ultrashort echo time–enhanced T2* (UTE-T2*), is correlated with (1) worse patient-reported knee function and pain and (2) gait metrics related to patellofemoral tracking and loading, such as greater external rotation of the tibia at heel strike, reduced knee flexion moment (as a surrogate of quadriceps function), and greater knee flexion angle at heel strike. Study Design: Cross-sectional study; Level of evidence, 3. Methods: MRI UTE-T2* relaxation times in patellar and trochlear deep cartilage were compared with patient-reported outcomes and ambulatory gait metrics in 60 patients with ACLR at 2 years after reconstruction. ACLR gait metrics were compared with those of 60 uninjured reference patients matched by age, body mass index, and sex. ACLR UTE-T2* values were compared with those of 20 uninjured reference patients. Results: Higher trochlear UTE-T2* values were associated with worse Knee injury and Osteoarthritis Outcome Scores (KOOS) Sport/Recreation subscale scores (rho = −0.32; P = .015), and showed a trend for association with worse KOOS Pain subscale scores (rho = −0.26; P = .045). At 2 years after ACLR, greater external rotation of the tibia at heel strike was associated with higher patellar UTE-T2* values ( R = 0.40; P = .002); greater knee flexion angle at heel strike was associated with higher trochlear UTE-T2* values (rho = 0.39; P = .002); and greater knee flexion moment showed a trend for association with higher trochlear UTE-T2* values (rho = 0.30; P = .019). Patellar cartilage UTE-T2* values, knee flexion angle at heel strike, and external rotation of the tibia at heel strike were all elevated in ACLR knees as compared with reference knees ( P = .029, .001, and .044, respectively). Conclusion: Patellofemoral deep cartilage matrix disruption, as assessed by MRI UTE-T2*, was associated with reduced sports and recreational function and with gait metrics reflective of altered patellofemoral loading. As such, the findings provide new mechanistic information important to improving clinical outcomes related to patellofemoral dysfunction after ACLR.

ABSTRACT Alteration of deep cartilage matrix has been observed following anterior cruciate ligament (ACL) injury, evidenced by elevated MRI UTE‐T2* values measured in small, 2‐D cartilage regions of interest. This Level I diagnostic study seeks to more thoroughly evaluate deep cartilage matrix changes to medial tibiofemoral UTE‐T2* maps 2 years after ACL reconstruction and examine the relative utilities of 3‐D compared to 2‐D assessments of cartilage UTE‐T2* maps. Thirty‐eight ACL‐reconstructed and 20 uninjured subjects underwent MRI UTE‐T2* mapping. “Small” single mid‐sagittal 2‐D and larger 3‐D “tread mark” regions of interest were manually segmented and found to be correlated in medial cartilage ( r > 0.58, p < 0.005). 3‐D analyses of UTE‐T2* maps showed differences to medial tibial cartilage between ACL‐reconstructed and uninjured subjects ( p = 0.007) that were not detected by smaller 2‐D regions ( p > 0.46). Quantitative comparisons show 14/38 (37%) ACL‐reconstructed subjects have values >2 standard deviations higher than uninjured controls. Among a subset of ACL‐reconstructed subjects with no morphologic MRI evidence of medial tibiofemoral cartilage or meniscal pathology ( n = 12), elevated UTE‐T2* values in “small” 2‐D femoral ( p = 0.011), but not larger 3‐D tread mark regions of interest ( p > 0.13), were observed. These data show the utility of 2‐D UTE‐T2* assessments of mid‐sagittal weight‐bearing regions of medial femoral cartilage for identifying subclinical deep cartilage matrix changes 2 years after ACLR. Clinical Significance: Mid‐sagittal single slice 2‐D UTE‐T2* mapping may be an efficient means to assess medial femoral cartilage for subsurface matrix changes early after ACL reconstruction while 3‐D assessments provide additional sensitivity to changes in the medial tibial plateau. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:370–377, 2019.

BACKGROUND:Noninvasive quantitative magnetic resonance imaging (MRI) measures to assess anterior cruciate ligament (ACL) graft maturity are needed to help inform return to high-demand activities and to evaluate the effectiveness of new treatments to accelerate ACL graft maturation. Quantitative MRI ultrashort echo time T2* (UTE-T2*) and T2* mapping captures short T2 signals arising from collagen-associated water in dense regular connective tissues, such as tendon, ligament, and maturing grafts, which are invisible to conventional MRI. HYPOTHESIS:Quantitative MRI UTE-T2* and T2* mapping is sensitive to ACL graft changes over the first 2 years after ACL reconstruction (ACLR). STUDY DESIGN:Case series; Level of evidence, 4. METHODS:A total of 32 patients (18 men; mean ± SD age, 30 ± 9 years) undergoing unilateral ACLR and 30 uninjured age-matched controls (18 men; age, 30 ± 9 years) underwent 3-T MRI examination. Patients who underwent ACLR were imaged at 6 weeks, 6 months, and 1 and 2 years postoperatively. Two separate ACLR cohorts were scanned with 2 MRI platforms at 2 institutions. Twelve ACLR knees were scanned with a 3-dimensional acquisition-weighted stack of spirals UTE sequence on a Siemens scanner, and 20 ACLR knees were scanned with a 3-dimensional Cones UTE sequence on a GE scanner. UTE-T2* or T2* maps were calculated for the intra-articular portion of the ACL graft. RESULTS:Mean ACL graft UTE-T2* and T2* decreased from 1 to 2 years after ACLR. ACL graft T2* increased 25% to 30% during the first 6 months (P < .013) to a level not different from that of uninjured native ACL (P > .4), stabilized between 6 months and 1 year (P ≥ .999), and then decreased 19% between 1 and 2 years after ACLR (P = .027). At 6-month follow-up, ACL graft UTE-T2* differed from that of tendon (P < .02) but not uninjured native ACL (P > .7) and showed the greatest variability among patients. CONCLUSION:UTE-T2* mapping suggested substantial changes within the graft during the first 6 months postsurgery. T2* and UTE-T2* mapping showed relatively stable graft composition from 6 months to 1 year, consistent with remodeling, followed by decreases from 1 to 2 years, suggestive of continuing maturation. MRI UTE-T2* and T2* mapping demonstrated potential clinical utility as noninvasive quantitative imaging metrics for evaluation of human ACL grafts.