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This study aims to determine if baseline T1ρ and T2 will predict cartilage morphological lesion progression in the patellofemoral joint (PFJ) and patient‐reported outcomes at 2‐year after anterior cruciate ligament (ACL) reconstruction (ACLR). Thirty‐nine ACL‐injured patients were studied at baseline and two‐year after ACLR. 3 T MR T1ρ and T2 images and Knee Injury and Osteoarthritis Outcome Score (KOOS) were acquired at both time points. Voxel‐based relaxometry (VBR) technique was used to detect local cartilage abnormalities. Patients were divided into progression and non‐progression groups based on changes of the whole‐organ magnetic resonance imaging scoring (WORMS) grading of cartilage in PFJ from baseline to 2‐year, and into lower (more pain) and higher (less pain) KOOS pain groups based on 2‐year KOOS pain scores, separately. Voxel‐based analyses of covariance were used to compare T1ρ and T2 values at baseline between the defined groups. Using VBR analysis, the progression group at 2‐year showed higher T1ρ and T2 compared with the non‐progression group at baseline, with the medial femoral condyle showing the largest areas with significant differences. At two‐year, 56% of patients were able to recover with respect to KOOS pain. The lower KOOS pain group at 2‐year showed significantly elevated T1ρ and T2 in the patella at baseline compared with the higher KOOS pain group. In conclusion, baseline T1ρ and T2 mapping, combined with VBR analysis, may help identify ACLR patients at high risk of developing progressive PFJ cartilage lesions and worse clinical symptoms 2‐year after surgery. [ABSTRACT FROM AUTHOR]

To determine the cross‐sectional and longitudinal associations of patella alignment with cartilage relaxation and patients' self‐reported symptoms. Thirty participants with isolated patellofemoral joint (PFJ) degeneration (six males, 53.7 ± 9.3 years) and 24 controls (12 males, 47.6 ± 10.7 years) were included. Magnetic resonance assessment was performed to provide grading of structural abnormalities, cartilage relaxation times, and patella alignment. Self‐reported symptoms were assessed using the self‐administrated knee injury and osteoarthritis outcome score (KOOS). All participants were examined at baseline and 3 years. Statistical parametric mapping and Pearson partial correlation were used to evaluate the associations between patella alignment with cartilage relaxation times and self‐reported symptoms, respectively. The analyses were performed between baseline (cross‐sectional) as well as the baseline against 3 years (longitudinal). Results indicated that patella height and patella flexion were associated with T1ρ and T2 relaxation times at baseline (percentages of voxels showing significant correlation [PSV] = 10.1%–24.8%; mean correlations [R] = 0.34–0.36; mean p = 0.015–0.026). Furthermore, greater patella lateral alignment, lateral tilt, and lateral spin were associated with longer T2 times at 3 years (PSV = 11.0%–14.4%, R = 0.39–0.44, p = 0.017–0.028). Last, a higher patella was associated with a lower KOOS at baseline and at 3 years (R = −0.33 to −0.35). The study suggests that patella malalignment is a risk factor for worsening cartilage health, informing clinicians of a better rehabilitation program that targets PFJ degeneration. [ABSTRACT FROM AUTHOR]

The aims of this case‐control study were to: (1) Identify cartilage locations and volumes at risk of osteoarthritis (OA) using subject‐specific finite element (FE) models; (2) Quantify the relationships between the simulated biomechanical parameters and T2 and T1ρ relaxation times of magnetic resonance imaging (MRI). We created subject‐specific FE models for seven patients with anterior cruciate ligament (ACL) reconstruction and six controls based on a previous proof‐of‐concept study. We identified locations and cartilage volumes susceptible to OA, based on maximum principal stresses and absolute maximum shear strains in cartilage exceeding thresholds of 7 MPa and 32%, respectively. The locations and volumes susceptible to OA were compared qualitatively and quantitatively against 2‐year longitudinal changes in T2 and T1ρ relaxation times. The degeneration volumes predicted by the FE models, based on excessive maximum principal stresses, were significantly correlated (r = 0.711, p < 0.001) with the degeneration volumes determined from T2 relaxation times. There was also a significant correlation between the predicted stress values and changes in T2 relaxation time (r = 0.649, p < 0.001). Absolute maximum shear strains and changes in T1ρ relaxation time were not significantly correlated. Five out of seven patients with ACL reconstruction showed excessive maximum principal stresses in either one or both tibial cartilage compartments, in agreement with follow‐up information from MRI. Expectedly, for controls, the FE models and follow‐up information showed no degenerative signs. Our results suggest that the presented modelling methodology could be applied to prospectively identify ACL reconstructed patients at risk of biomechanically driven OA, particularly by the analysis of maximum principal stresses of cartilage. [ABSTRACT FROM AUTHOR]

Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient‐specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro‐inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage–synovial fluid‐interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease‐modifying drug testing and rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Clinicians often examine movement patterns to design hip osteoarthritis (OA) interventions, yet traditional biomechanical analyses only report a single timepoint. Multivariate principal component analysis (MFPCA) analyzes the entire waveform (i.e., movement pattern), which clinicians observe to direct treatment. This study investigated hip OA indicators, by (1) employing MFPCA to characterize variance across the hip, knee, and ankle angles in healthy and early‐to‐moderate hip OA participants; and (2) investigating relationships between these waveform features and hip cartilage health. Bilateral hip magnetic resonance images from 72 participants with Kellgren–Lawrence grades ranging from 0 to 3 were used to calculate mean T1ρ and T2 relaxation times in the femoral and acetabular cartilage. MFPCA was performed on lower‐limb gait biomechanics and used to identify primary modes of variation, which were related to T1ρ and T2 relaxation times. Here, a MFPC = mode of variation = waveform feature. In the femoral cartilage, transverse plane MFPCs 3 and 5 and body mass index (BMI) was related to T1ρ, while MFPC 2 and BMI were related to T2 relaxation times. In the acetabular cartilage, sagittal plane MFPC 1 and BMI were related to T1ρ, while BMI was related to T2 relaxation times. Greater internal rotation was related to increased T1ρ and T2 relaxation times in the femoral cartilage, while the greater extension was related to increased T1ρ relaxation times in the acetabular cartilage. This study established a data‐driven framework to assess relationships between multi‐joint biomechanics and quantitative assessments of cartilage health and identified waveform features that could be evaluated in future hip OA intervention studies. [ABSTRACT FROM AUTHOR]

The purpose of this proof‐of‐concept study was to develop three‐dimensional patient‐specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T1ρ and T2 relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T1ρ and T2 relaxation times increased during the follow‐up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof‐of‐concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects. [ABSTRACT FROM AUTHOR]

The relationship between morphological characteristics of the hip capsule and patient symptoms in the setting of femoroacetabular impingement (FAI) is undefined. In this study, patients with symptomatic FAI prospectively underwent 3T magnetic resonance (MR) imaging of the affected hip and completed the hip disability and osteoarthritis outcome score (HOOS) to determine the correlation between hip capsule anatomy and patient symptoms. Anterior hip capsule volume, posterior capsule volume, anterior‐posterior capsule volume ratio, and proximal‐distal volume ratio in the anterior capsule were quantified and measured using axial‐oblique intermediate‐weighted 3D fast spin echo MR images. A total of 35 patients (35 hips) were included for analysis (mean age: 30.6 years; mean body mass index [BMI]: 24.9 kg/m2; 57% male). The mean alpha angle was 62.2° ± 4.7°, the mean anterior hip capsule volume was 1705.1 ± 450.3 mm3, the mean posterior hip capsule volume was 1284.8 ± 268.5 mm3, the mean anterior to posterior capsule volume ratio was 1.1 ± 0.39, and the mean proximal to distal volume ratio of the anterior capsule was 0.65 ± 0.28. There was no correlation between age, gender, or BMI, and any hip capsule characteristics. Worse scores on the HOOS pain scale were correlated with increased anterior to posterior volume ratio (r = −.38; 95% confidence interval: −0.06 to −0.63). In conclusion, hip capsule morphology correlates with patient symptoms in the setting of FAI as increased anterior capsular volume, relative to posterior capsular volume, is associated with greater patient pain. [ABSTRACT FROM AUTHOR]

To explore bone shape features that are associated with patellofemoral joint (PFJ) osteoarthritic features. Thirty subjects with PFJ degeneration (six males, 53.2 ± 9.8 years) and 23 controls (12 males, 48.1 ± 10.6 years) were included. Magnetic resonance (MR) assessment was performed to provide bone segmentation, morpholgocial grading, and cartilage relaxation times. In addition, subject self‐reported symptoms were reported. Logistic regressions were used to identify the shape features that were associated with the presence and worsening of PFJ morphological lesions over 3 years, and worsening of self‐reported symptoms. Statistical parametric mapping was used to evaluate the associations between shape features and cartilage relaxation times at 3 years. Results indicated that subjects with PFJ degeneration exhibited a trochlea with longer lateral condyle and shallower trochlear groove (adjusted odds ratio [OR] = 0.30; 95% confidence interval [CI]: 0.10, 0.86; P =.025). Subjects with worsening of PFJ degeneration exhibited a patella with equally distributed facets (adjusted OR = 3.14; 95% CI: 1.05, 9.37; P =.040) and lateral bump (adjusted OR = 0.14; 95% CI: 0.02, 0.83; P =.030). No shape features were associated with worsening of self‐reported symptoms. Elevated T1ρ and T2 times at 3 years were associated with a patella with a lateral hook, equally distributed facets, round and thick as well as a trochlea larger in size (R = 0.38~0.46, P =.015~.025). The study demonstrated the ability of 3D statistical shape modeling to quantify patella and trochlear bone shape features that are associated with the presence and progression of PFJ osteoarthritic features. [ABSTRACT FROM AUTHOR]

While substantial work has been done to understand the relationships between cartilage T2 relaxation times and osteoarthritis (OA), diagnostic and prognostic abilities of T2 on a large population yet need to be established. Using 3921 manually annotated 2D multi‐slice multi‐echo spin‐echo magnetic resonance imaging volume, a segmentation model for automatic knee cartilage segmentation was built and evaluated. The optimized model was then used to calculate T2 values on the entire osteoarthritis initiative (OAI) dataset composed of longitudinal acquisitions of 4796 unique patients, 25 729 magnetic resonance imaging studies in total. Cross‐sectional relationships between T2 values, OA risk factors, radiographic OA, and pain were analyzed in the entire OAI dataset. The performance of T2 values in predicting the future incidence of radiographic OA as well as total knee replacement (TKR) were also explored. Automatic T2 values were comparable with manual ones. Significant associations between T2 relaxation times and demographic and clinical variables were found. Subjects in the highest 25% quartile of tibio‐femoral T2 values had a five times higher risk of radiographic OA incidence 2 years later. Elevation of medial femur T2 values was significantly associated with TKR after 5 years (coeff = 0.10; P =.036; CI = [0.01,0.20]). Our investigation reinforces the predictive value of T2 for future incidence OA and TKR. The inclusion of T2 averages from the automatic segmentation model improved several evaluation metrics when compared to only using demographic and clinical variables. [ABSTRACT FROM AUTHOR]

This study characterized the distribution of [18F]‐sodium fluoride (NaF) uptake and blood flow in the femur and acetabulum in hip osteoarthritis (OA) patients to find associations between bone remodeling and cartilage composition in the presence of morphological abnormalities using simultaneous positron emission tomography and magnetic resonance imaging (PET/MR), quantitative magnetic resonance imaging (MRI) and femur shape modeling. Ten patients underwent a [18F]‐NaF PET/MR dynamic scan of the hip simultaneously with: (i) fast spin‐echo CUBE for morphology grading and (ii) T1ρ/T2 magnetization‐prepared angle‐modulated partitioned k‐space spoiled gradient echo snapshots for cartilage, bone segmentation, bone shape modeling, and T1ρ/T2 quantification. The standardized uptake values (SUVs) and Patlak kinetic parameter (Kpat) were calculated for each patient as PET outcomes, using an automated post‐processing pipeline. Shape modeling was performed to extract the variations in bone shapes in the patients. Pearson's correlation coefficients were used to study the associations between bone shapes, PET outcomes, and patient reported pain. Direct associations between quantitative MR and PET evidence of bone remodeling were established in the acetabulum and femur. Associations of shaft thickness with SUV in the femur (p = 0.07) and Kpat in the acetabulum (p = 0.02), cam deformity with acetabular score (p = 0.09), osteophytic growth on the femur head with Kpat (p = 0.01) were observed. Pain had increased correlations with SUV in the acetabulum (p = 0.14) and femur (p = 0.09) when shaft thickness was accounted for. This study demonstrated the ability of [18F]‐NaF PET‐MRI, 3D shape modeling, and quantitative MRI to investigate cartilage‐bone interactions and bone shape features in hip OA, providing potential investigative tools to diagnose OA. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 37:2671–2680, 2019 [ABSTRACT FROM AUTHOR]

The goal of this study was to use quantitative MRI analysis to longitudinally observe the relationship between 3D proximal femur shape and hip joint degenerative changes. Forty‐six subjects underwent unilateral hip MR imaging at three time points (baseline, 18 and 36 months). 3D shape analysis, hip cartilage T1ρ/T2 relaxation time quantification, and SHOMRI MRI grading were performed at each time point. Subjects were grouped based on KL, SHOMRI, and HOOS pain scores. Associations between these score groupings, time, and longitudinal variation in shape, were analyzed using a generalized estimating equation. One‐way ANCOVA was conducted to evaluate change in shape as a predictor of the worsening of degenerative changes at 36 months. Our results demonstrated that subjects displayed an increase in the volume of the femoral head and neck (Mode 3) over time. This shape mode was significantly more prevalent in patients that reported pain. Longitudinal changes in this shape mode also served as borderline predictors of elevated T1ρ values (p = 0.055) and of cartilage lesions (p = 0.068). Subjects showed a change in the Femoral Neck Anteversion angle (FNA) over time (Mode 6). This shape mode showed a significant interaction with the presence of cartilage lesions. The results of this study suggest that specific variations in bone shape quantified through 3D‐MRI based Statistical Shape modeling show an observable relationship with hip joint compositional and morphological changes. The shapes observed lead to early degenerative changes, which may lead into OA, thus confirming the important role of bone shape changes in the pathogenesis of OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

ABSTRACT: The purpose was to evaluate the association of sagittal plane gait mechanics with MRI changes in the hip joint over 18‐months. Subjects with and without radiographic hip OA (n = 57) underwent MRI at baseline and 18 months for grading of cartilage lesions, bone marrow lesions (BML), cysts, and labral tears. 3D gait analyses at baseline were used for sagittal plane hip kinematics and kinetics during the stance phase. Subjects were classified as progressors or non‐progressors based on increase in any MRI OA parameter. Multivariate ANOVA were used for differences in sagittal gait parameters between progressors and non‐progressors at baseline while adjusting for age. Logistic regression was used to estimate the probability of being classified as a progressor or non‐progressor with increasing hip flexion while adjusting for age, BMI, sex, and presence of radiographic hip OA. Of the 57, 35 were classified as non‐progressors and 22 were classified as progressors. At baseline, the progressors walked with 4.5° greater hip flexion during early stance (p = 0.021) and 3.5° lesser hip extension in late stance that was nearly significant (p = 0.059). Walking with greater hip flexion at baseline was associated with a greater risk of increase in MRI defined structural changes in the hip joint (Odds Ratio = 1.1, p = 0.038). Greater hip flexion during walking was associated with a risk of structural progression of hip OA. The results may guide future interventions to alter the walking patterns and slow structural hip OA progression.© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1472–1477, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT: In this study, quantitative magnetic resonance based measurements were used to evaluate T1ρ and T2 mapping and heterogeneity in femoroacetabular impingement (FAI) patients with acetabular cartilage delamination and to determine the ability of these quantitative MR‐based measurements in detecting delamination. Unilateral hip joint MR‐scans of 36 FAI patients with arthroscopically‐confirmed acetabular cartilage delamination and 36 age, gender, and BMI matched controls were obtained. T1ρ and T2 mapping and heterogeneity of the hip joint articular cartilage were assessed in both groups using voxel‐based relaxometry (VBR). Quantitative MR‐based measurements were compared using statistical parametric mapping (SPM). Receiver operating characteristic (ROC) analysis was used to assess the ability of these quantitative measurements in detecting delamination by calculating the area under the curve (AUC). Pearson partial correlations (r) were used to assess for associations between T1ρ and T2 radial heterogeneity with the alpha angle in FAI patients. T1ρ and T2 global acetabular values were significantly higher in FAI patients with a focal increase within the posterior acetabular cartilage. FAI patients exhibited increased anterior superior acetabular T1ρ and T2 heterogeneity and both of these measures demonstrated a strong ability to detect acetabular cartilage delamination (T1ρ AUC: 0.96, p < 0.001; T2 AUC: 0.93, p < 0.001). FAI patients with a larger alpha angle exhibited increased anterior superior acetabular T1ρ (r = 0.48, p = 0.02) and T2 (r = 0.42, p = 0.03) heterogeneity. T1ρ and T2 heterogeneity within the anterior superior acetabular cartilage was shown to be a sensitive measure in detecting delamination and may prove beneficial to clinicians in determining optimal interventions for FAI patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:971–978, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT The objectives of this study were twofold: (1) to evaluate the longitudinal change in cartilage T1ρ and T2 6- and 12-months after ACL reconstruction (ACLR) in both reconstructed and intact contralateral knees with the aim of validating the role of the contralateral knee as an internal control in longitudinal studies; (2) to explore relationships between bone shape at the time of injury and the progression of T1ρ and T2 over 12-months after ACLR. T1ρ and T2 cartilage relaxation times and 3D MRI-based statistical shape modeling (SSM) of tibia and femur were computed for both knees of forty ACL-injured patients and 15 healthy controls. ACL subjects were scanned 8.4 ± 6.4 weeks after injury (2.4 ± 3.7 weeks prior to ACLR), 6- and 12-months after ACLR. Longitudinal changes in T1ρ and T2 values were assessed using linear mixed model, and partial correlation coefficients were calculated between bone shape and longitudinal changes in T1ρ and T2 values. Significant longitudinal increases in T1ρ and T2 values were observed in reconstructed and contralateral knees 6-months after ACLR. Tibial bone shape features, associated with the medial plateau height and width, were observed to be correlated with cartilage T1ρ and T2 progression in reconstructed knees. Our results suggest that caution should be used in considering contralateral knee as internal controls in longitudinal ACL studies and 3D MRI-based-SSM might serve as an imaging biomarker for the early stratification of patients at risk for developing post-traumatic accelerated cartilage degeneration and potentially osteoarthritis after ACL tear. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:707-717, 2017. [ABSTRACT FROM AUTHOR]