Machine learning to predict incident radiographic knee osteoarthritis over 8 Years using combined MR imaging features, demographics, and clinical factors: data from the Osteoarthritis Initiative.

OBJECTIVE: To develop a machine learning-based prediction model for incident radiographic osteoarthritis (OA) of the knee over 8 years using MRI-based cartilage biochemical composition and knee joint structure, demographics, and clinical predictors including muscle strength and symptoms. DESIGN: Individuals (n = 1,044) with baseline Kellgren Lawrence (KL) grade 0-1 in the right knee from the Osteoarthritis Initiative database were analyzed. 3T MRI at baseline was used to quantify knee cartilage T2, and Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone marrow. The outcome was set as true if a subject developed KL grade 2-4 OA in the right knee over 8 years (n = 183) and false if the subject remained at KL 0-1 over 8 years (n = 861). We developed and compared three models: Model 1: 112 predictors based on OA risk factors; Model 2: top ten predictors based on feature importance score from Model 1 and clinical relevance; Model 3: Model 2 without the imaging predictors. We compared the models using the area under the ROC curve derived from hold-out data. RESULTS: The 10-predictor model (Model 2, that includes cartilage and meniscus WORMS scores and cartilage T2) had a slightly lower AUC (0.772) compared to the model with 112 predictors (Model 1: AUC = 0.792, p = 0.739); and had a significantly higher AUC compared to the model without MR imaging predictors (Model 3, AUC = 0.669, p = 0.011). CONCLUSIONS: A 10-predictor model including MRI parameters coupled with demographics, symptoms, muscle, and physical activity scores provides good prediction of incident radiographic OA over 8 years.

Anterior cruciate ligament abnormalities are associated with accelerated progression of knee joint degeneration in knees with and without structural knee joint abnormalities: 96-month data from the Osteoarthritis Initiative.

OBJECTIVE: To compare progression over 8 years in knee compositional cartilage degeneration and structural joint abnormalities in knees with different types of anterior cruciate ligament (ACL) abnormalities over 8 years. METHOD: Baseline MR images of the right knees of 1899 individuals of the Osteoarthritis Initiative (OAI) with no evidence of or mild to moderate radiographic osteoarthritis were assessed for nontraumatic ACL abnormalities. The knees of 91 individuals showed nontraumatic ACL abnormalities (age 60.6 ± 9.8 y, 46 females; mucoid degeneration (MD), N = 37; complete tear (CT), N = 22; partial tear (PT), N = 32) and were frequency-matched to 91 individuals with normal ACL. MRIs were assessed for knee joint abnormalities using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and cartilage T2 mapping at baseline, 4- and 8-year follow-up. RESULTS: Over 8 years, cartilage T2 values of the medial tibia showed a significantly greater increase in individuals with MD, PT or CT compared to those with normal ACL (adjusted rate of change/year [95% confidence interval], normal ACL: 0.06 [0.01, 0.23], MD: 0.34 [0.07, 0.73], PT, 0.21 [0.02, 0.33], CT, 0.51 [0.16, 0.78]), indicating an association of ACL abnormalities and an increased progression rate of cartilage degeneration in subjects with and without knee joint degeneration. This effect was also seen in cartilage T2 values averaged over all compartments (normal ACL: 0.08 [0.05, 0.20] vs abnormal ACL: 0.27 [0.06, 0.56]). CONCLUSIONS: Over 8 years, higher progression rates of cartilage degeneration, especially in the medial tibia, were associated with ACL abnormalities compared to those with normal ACL, in subjects with and without knee joint abnormalities.

Impact of different physical activity types on knee joint structural degeneration assessed with 3-T MRI in overweight and obese subjects: data from the osteoarthritis initiative.

OBJECTIVE: To assess the impact of different types of physical activity types on longitudinal knee joint structural changes over 48 months in overweight and obese subjects. MATERIALS AND METHODS: We included 415 subjects with a BMI ≥ 25 kg/m2, Kellgren-Lawrence scores ≤ 3 at baseline and Whole-Organ Magnetic Resonance Imaging Score (WORMS) scores available from the Osteoarthritis Initiative cohort. Regular self-reported participation in six physical activity types was assessed: ball sports, bicycling, jogging/running, elliptical-trainer, racquet sports, and swimming. Moreover, they were classified into high- and low-impact physical activity groups. Evaluation of structural knee abnormalities was performed using WORMS obtained by two independent observers blinded to the subjects' physical activity and time point. Linear regression models were used to assess the associations between participation in different physical activity types and changes in WORMS. RESULTS: No significant differences in epidemiological data were found between the groups except for gender composition, and there were no significant differences in baseline WORMS. In the cohort as a whole and most exercise groups overall WORMS significantly increased during the observational period. Highest increases compared to the remainder of the group were found in the high impact group (increase in WORMS 4.65; [95% CI] [3.94,5.35]; p = 0.040) and the racquet sports group (6.39; [95% CI] [5.13,7.60]; p ≤ 0.001). Subjects using an elliptical-trainer showed the lowest increase in WORMS (- 1.50 [- 0.21, 3.22]; p = 0.002). CONCLUSION: Progression of knee joint degeneration was consistently higher in subjects engaging in high-impact and racquet sports while subjects using an elliptical-trainer showed the smallest changes in structural degeneration. This work was presented during the 2020 Radiological Society of North America Annual meeting.

Chondrocalcinosis is associated with increased knee joint degeneration over 4 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine if presence of calcium-containing crystals (CaC) is associated with increased knee joint degeneration over 4 years and assess if total number of CaCs deposited is a useful measure of disease burden. DESIGN: Seventy subjects with CaCs in right knees at baseline were selected from the Osteoarthritis Initiative and matched to 70 subjects without evidence of CaCs. T1-weighted gradient-echo sequences were used to confirm presence of CaCs and count the numbers of distinct circumscribed CaCs. Morphological abnormalities were assessed at baseline and 4-year follow-up using the modified semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression models were used to analyze the associations between presence of CaCs at baseline and changes in WORMS and to analyze the associations between numbers of circumscribed CaCs at baseline and changes in WORMS. RESULTS: Presence of CaCs was associated with increased cartilage degeneration in the patella (coefficient: 0.33; 95% confidence interval (CI): 0.04-0.63), the medial femur (coefficient: 0.51; 95% CI: 0.18-0.83), the lateral tibia (coefficient: 0.36; 95% CI: 0.01-0.71) as well as the medial and lateral meniscus (coefficient: 0.38; 95% CI: 0.00-0.75 and coefficient: 0.72; 95% CI: 0.12-1.32). Knees with higher numbers of CaCs had increased cartilage degeneration in the patella and medial femur (coefficient: 0.09; 95% CI: 0.05-0.14; P < 0.001 and coefficient: 0.08; 95% CI: 0.02-0.14; P = 0.005). CONCLUSIONS: CaCs were associated with increased cartilage and meniscus degeneration over a period of 4 years. Assessing the number of CaC depositions may be useful to evaluate risk of onset and worsening of degenerative disease.

Spatial distribution and temporal progression of T2 relaxation time values in knee cartilage prior to the onset of cartilage lesions - data from the Osteoarthritis Initiative (OAI).

PURPOSE: To investigate compositional changes of knee cartilage at the site of newly appearing cartilage lesions and the surrounding cartilage 1-4 years prior to lesion onset using quantitative T2-measurements. METHODS: Fifty-seven cartilage plates with newly appearing cartilage lesions from 45 knees (cases) and 52 plates from 26 control knees from the Osteoarthritis Initiative (OAI) cohort (controls) were evaluated. Using MRI T2-mapping, composition of local (the site of future lesions) and surrounding cartilage (remainder of the cartilage plate) was assessed 1-4 years prior to lesion onset. Analogous cartilage ROIs in control plates without cartilage lesions were assessed over 1-4 years. Mixed models were used to compare T2-means and change rates between local and surrounding cartilage within cases and controls, and to compare change rates in local and surrounding cartilage between cases and controls, adjusting for covariates. RESULTS: Four years prior to lesion onset, we found that local cartilage ROIs had higher T2-values compared to the surrounding cartilage. No such differences were found in control plates. In cases mean local T2-values were persistantly elevated compared to the surrounding cartilage prior to lesion onset reaching significance 1 year prior (+2.94 ms, p = 0.012). T2-values of the surrounding cartilage were also persistantly higher in cases compared to controls, reaching significance 2 years prior to lesion onset (+3.61 ms, p = 0.003). CONCLUSION: The findings of our study support the concept of compositional cartilage changes as a mechanism for cartilage degradation and that both diffuse and focal changes of cartilage composition within a cartilage plate precede the development of cartilage lesions.

Weight loss regimen in obese and overweight individuals is associated with reduced cartilage degeneration: 96-month data from the Osteoarthritis Initiative.

PURPOSE: To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss (WL), and to assess how different WL regimens are associated with these changes. METHODS: We studied right knees of 760 participants (age 62.6 ± 9.0y; 465 females) with a baseline body mass index (BMI) >25 kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N = 380) were compared to controls with stable weight (SW, N = 380). Participants losing weight were categorized based on WL method (diet and exercise, diet only, exercise only) and compared to those with stable weight. Magnetic resonance imaging (MRI) at 3T was performed at baseline, 48- and 96-months. The association of WL and WL method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models. RESULTS: Compared to SW, WL was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 (adjusted mean difference of change in T2 ms/year [95% CI] between the groups: 0.24 [0.20, 0.41] ms/year; P < 0.001) and global deep layer cartilage T2 0.35 [0.20, 0.42] ms/year; P < 0.001), suggesting slower cartilage deterioration. Compared to the SW group, slower increases in global T2 were observed in the diet and diet and exercise groups, but not in the exercise only group (P = 0.042, P = 0.003 and P = 0.85, respectively). CONCLUSION: Our results suggest that WL may slow knee cartilage degeneration over 96 months, and that these potential benefits may differ by method of WL.

Novel proteins that regulate cell extension formation in fibroblasts.

Cell extensions are critical structures that enable matrix remodeling in wound healing and cancer invasion but the regulation of their formation is not well-defined. We searched for new proteins that mediated cell extension formation over collagen by tandem mass tagged mass spectrometry analysis of purified extensions in 3T3 fibroblasts. Unexpectedly, importin-5, ENH isoform 1b (PDLIM5) and 26 S protease regulatory subunit 6B (PSMC4) were more abundant (> 10-fold) in membrane-penetrating cell extensions than cell bodies, which was confirmed by immunostaining and immunoblotting and also observed in human gingival fibroblasts. After siRNA knockdown of these proteins and plating cells on grid-supported floating collagen gels for 6 h, formation of cell extensions and collagen remodeling were examined. Knockdown of importin-5 reduced collagen compaction (1.9-fold), pericellular collagen degradation (~ 1.8-fold) and number of cell extensions (~ 69%). Knockdown of PSMC4 reduced collagen compaction (~ 1.5-fold), pericellular collagen degradation (~ 1.7-fold) and number of cell extensions (~ 42%). Knockdown of PDLIM5 reduced collagen compaction (~ 1.6-fold) and number of cell extensions (~ 21%). Inhibition of the TGF-ß RI kinase, Smad3 or ROCK-II signaling pathways reduced the abundance of PDLIM5 in cell extensions but PSMC4 and importin-5 were reduced only by Smad3 or ROCK-II inhibitors. We conclude that these novel proteins are required for cell extension formation and their recruitment into extensions involves the Smad3 and ROCK signaling pathways.

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

OBJECTIVE: The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN: 141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS: Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS: This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

Type 2 diabetes patients have accelerated cartilage matrix degeneration compared to diabetes free controls: data from the Osteoarthritis Initiative.

PURPOSE: Osteoarthritis (OA) and diabetes mellitus (DM) share common risk factors with a potential underlying relationship between both diseases. The purpose of this study was to investigate the longitudinal effects of DM on cartilage deterioration over 24-months with MR-based T2 relaxation time measurements. METHODS: From the Osteoarthritis Initiative (OAI) cohort 196 diabetics were matched in small sets for age, sex, BMI and Kellgren-Lawrence score with 196 non-diabetic controls. Knee cartilage semi-automatic segmentation was performed on 2D multi-slice multi-echo spin-echo sequences. Texture of cartilage T2 maps was obtained via grey level co-occurrence matrix analysis. Linear regression analysis was used to compare cross-sectional and changes in T2 and texture parameters between the groups. RESULTS: Both study groups were similar in age (63.3 vs 63.0 years, P = 0.70), BMI (30.9 vs 31.2 kg/m2, P = 0.52), sex (female 53.6% vs 54.1%, P = 0.92) and KL score distribution (P = 0.97). In diabetics, except for the patella, all compartments showed a significantly higher increase in mean T2 values when compared to non-diabetic controls. Global T2 values increased almost twice as much; 1.77ms vs 0.98ms (0.79ms [CI: 0.39,1.19]) (P < 0.001). Additionally, global T2 values showed a significantly higher increase in the bone layer (P = 0.006), and in a separate analysis of the texture parameters, diabetics also showed consistently higher texture values (P < 0.05), indicating a more disordered cartilage composition. CONCLUSION: Cartilage T2 values in diabetics show a faster increase with a consistently more heterogeneous cartilage texture composition. DM seems to be a risk factor for developing early OA with an accelerated degeneration of the articular cartilage in the knee.

A novel, cell-permeable, collagen-based membrane promotes fibroblast migration.

BACKGROUND AND OBJECTIVE: Growth factors are frequently incorporated into scaffolds to promote periodontal regeneration but many currently used scaffolds do not encourage cell migration towards the dentogingival junction. We examined the proliferation and migration of human gingival fibroblasts in a novel, physically robust, collagen-Vicryl™ membrane loaded with fibronectin (FN) and/or insulin-like growth factor (IGF-I). Biocompatibility of the membranes was evaluated in rat dorsal skin. MATERIAL AND METHODS: Chemotaxis was examined in Boyden chambers and cell migration by confocal imaging of membranes, which were fabricated from rat tail type I collagen with embedded Vicryl knitted mesh, IGF-I (50, 100 ng/mL) and FN (10 µg/mL). Membranes (Vicryl alone, collagen+Vicryl, collagen+Vicryl+IGF-I, collagen+Vicryl+FN') were implanted subcutaneously in 8 rats and were evaluated by histomorphometry after 7 and 14 days. RESULTS: IGF-I (50 or 100 ng/mL) promoted chemotaxis compared with vehicle controls (P = .02, P = .001, respectively). IGF-I did not affect cell proliferation. Incorporation of FN retarded time-dependent release of IGF-I from collagen gels. Three dimensional confocal microscopy imaging of cell migration through collagen+Vicryl membranes showed enhanced migration in the IGF+FN group compared to all other groups at 8, 10 and 14 days (P < .05). In a rat skin model, implanted membranes were surrounded by thin collagen capsules and mild inflammatory infiltrates. CONCLUSION: Incorporation of FN into IGF-I-loaded collagen+Vicryl membranes reduced IGF release from collagen and increased the migration of human gingival fibroblasts. The new membrane may promote healing and reformation of the dentogingival junction.

PAK1 is involved in sensing the orientation of collagen stiffness gradients in mouse fibroblasts.

Migrating cells sense variations of stiffness in connective tissue matrices but how cells detect and respond to stiffness orientation is not defined. We examined cell extension formation on collagen with underlying support (vertical stiffness gradient) or on collagen laterally supported by nylon (lateral stiffness gradient). At 6 h after plating, cells plated on laterally-supported collagen exhibited >2-fold more abundant and ~2-fold longer cell extensions than cells plated on collagen with underlying support. We examined whether p21-activated kinase 1 (PAK1) influences extension formation that is dependent on the orientation of support. At 6 h after plating on collagen with underlying support, wild-type cell extensions were 40% shorter than PAK1 knockdown cells. In contrast, on laterally-supported collagen, wild-type cell extensions were 2-fold longer than PAK1 knockdown cells. In cells plated on laterally-supported collagen, there were ~2-fold reductions of collagen fiber alignment and compaction in PAK1 knockdown cells compared with wild-type cells. PAK1 knockdown did not affect collagen fiber alignment or compaction by cells plated on collagen with underlying support. Wild-type cells with lateral support of collagen exhibited 3-fold increases of phospho-myosin staining at 6h, which was 2-fold lower in PAK1 knockdown cells. In contrast, cells on collagen with underlying support showed no increase of phospho-myosin staining at any times. PAK1 knockdown did not affect α2 or ß1 integrin expression or function. We conclude that PAK1 is involved in the ability of cells to sense the orientation of stiffness in collagen substrates and generate contractile forces that affect cell extension formation.

Role of thigh muscle cross-sectional area and strength in progression of knee cartilage degeneration over 48 months - data from the Osteoarthritis Initiative.

OBJECTIVE: To determine in a 48-month longitudinal study the association of thigh muscle cross-sectional area (CSA) and strength on progression of morphologic knee cartilage degeneration using 3T magnetic resonance imaging (MRI). DESIGN: Seventy Osteoarthritis Initiative (OAI) subjects aged 50-60 years, with no radiographic evidence of osteoarthritis (OA) and constant muscle strength over 48 months as measured by isometric knee extension testing were included. Baseline right thigh muscle CSAs were assessed on axial T1-weighted magnetic resonance (MR) images, and extensor to flexor CSA ratios were calculated. Degenerative knee abnormalities at baseline and 48-months were graded on right knee 3T MRIs using a modified whole organ MRI score (WORMS). Statistical analysis employed Student's t-tests and multivariable regression models adjusted for age, body mass index and gender. RESULTS: Extension strength was significantly and positively correlated with baseline thigh muscle CSA (r = 0.65, P < 0.001). Greater baseline total thigh muscle CSA was significantly associated with increase of cartilage WORMS scores over 48 months in patellar (P = 0.027) and trochlear (P = 0.038) compartments, but not in other knee compartments. Among specific muscle groups, CSA of extensors (P = 0.021) and vastus medialis (VM) (P = 0.047) were associated with patellar cartilage increase in WORMS. Baseline E/F ratio had a significant positive association with patellar WORMS cartilage score increase over 48 months, P = 0.0015. There were no other significant associations between muscle CSA/ratios and increase in WORMS scores. CONCLUSION: Maintenance of proper extensor to flexor muscle balance about the knee through decreased E/F ratios may slow patellofemoral cartilage deterioration, while higher extensor and VM CSA may increase patellofemoral cartilage loss.

The association between MR T1ρ and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction.

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 (TrF) was associated with worse KOOS activities of daily living (ADL) 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.

Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate compositional cartilage changes measured with 3T MRI-based T2 values over 48 months in overweight and obese individuals with different degrees of weight loss (WL) and to study whether WL slows knee cartilage degeneration and symptom worsening. DESIGN: We studied participants from the Osteoarthritis Initiative with risk factors or radiographic evidence of mild to moderate knee osteoarthritis with a baseline BMI ≥25 kg/m(2). We selected subjects who over 48 months lost a, moderate (BMI change, 5-10%WL, n = 180) or large amount of weight (≥10%WL, n = 78) and frequency-matched these to individuals with stable weight (<3%, n = 258). Right knee cartilage T2 maps of all compartments and grey-level co-occurrence matrix (GLCM) texture analyses were evaluated and associations with WL and clinical symptoms (WOMAC subscales for pain, stiffness and disability) were assessed using multivariable regression models. RESULTS: The amount of weight change was significantly associated with change in cartilage T2 of the medial tibia (ß 0.9 ms, 95% CI 0.4 to 1.1, P = 0.001). Increase of T2 in the medial tibia was significantly associated with increase in WOMAC pain (ß 0.5 ms, 95% CI 0.2 to 0.6, P = 0.02) and disability (ß 0.03 ms, 95% CI 0.003 to 0.05, P = 0.03). GLCM contrast and variance over all compartments showed significantly less progression in the >10%WL group compared to the stable weight group (both comparisons, P = 0.04). CONCLUSIONS: WL over 48 months is associated with slowed knee cartilage degeneration and improved knee symptoms.

Longitudinal analysis of cartilage T2 relaxation times and joint degeneration in African American and Caucasian American women over an observation period of 6 years - data from the Osteoarthritis Initiative.

OBJECTIVES: To investigate the change in cartilage T2 values and structural degeneration in knee joints over 72 months in women of African American (AA) vs Caucasian American (CA) ethnicity. METHODS: Knee 3T magnetic resonance imaging (MRIs) from baseline, 24, 48 and 72 months visits of 100 AA and 100 CA women from the Osteoarthritis Initiative (OAI) were assessed for cartilage T2 values and whole-organ magnetic resonance imaging (WORMS) score. Subjects were pair-matched by age, body mass index (BMI), Kellgren-Lawrence (KL) score, clinical site and subcohort within the OAI. We compared the rate of change in whole knee cartilage T2 values and WORMS cartilage, bone marrow edema pattern (BMEP) and meniscus scores between the two ethnic groups using mixed random effects models. RESULTS: At 24 and 48 months 60 subjects and at 72 months 45 subjects per group were available for analysis resulting in 38 complete pairs with data of all time points. Compared to CA, cartilage T2 values in AA increased at a significantly faster rate at baseline (AA: 0.45 ms/y, CA: 0.35 ms/y, P = 0.029) and averaged over 6 years (AA: 0.36 ms/y, CA: 0.27 ms/y, P = 0.039) with changes in both groups reaching a plateau by 48 months. Cartilage, meniscus and BMEP scores tended to increase in both groups during follow up, but rates of change did not differ by ethnicity. CONCLUSION: Cartilage T2 values increased faster over 72 months in AA than CA, however changes in WORMS cartilage, meniscus and BMEP scores did not differ. T2 values may be able to distinguish ethnicity-related differences of cartilage degeneration at an early stage before differences in structural joint degeneration appear.

Do persons with asymmetric hip pain or radiographic hip OA have worse pain and structure outcomes in the knee opposite the more affected hip? Data from the Osteoarthritis Initiative.

PURPOSE: To determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips. METHODS: We studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations. RESULTS: Knees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17). CONCLUSION: These findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

Three-dimensional MRI-based statistical shape model and application to a cohort of knees with acute ACL injury.

OBJECTIVE: The aim of this study is to develop a novel 3D magnetic resonance imaging (MRI)-based Statistical Shape Modeling (SSM) and apply it in knee MRIs in order to extract and compare relevant shapes of the tibia and femur in patients with and without acute Anterior cruciate ligament (ACL) injuries. METHODS: Bilateral MR images were acquired and analyzed for 50 patients with acute ACL injuries and for 19 control subjects. A shape model was extracted for the tibia and femur using an SSM algorithm based on a set of matched landmarks that are computed in a fully automatic manner. RESULTS: Shape differences were detected between the knees in the ACL-injury group and control group, suggesting a common shape feature that may predispose these knees to injury. Some of the detected shape features that discriminate between injured and control knees are related to intercondylar width and posterior tibia slope, features that have been suggested in previous studies as ACL morphological risk factors. However, shape modeling has the great potential to quantify these characteristics with a comprehensive description of the surfaces describing complex 3D deformation that cannot be represented with simple geometric indexes. CONCLUSIONS: 3D MRI-based bone shape quantification has the ability to identify specific anatomic risk factors for ACL injury. A better understanding of the role in bony shape on ligamentous injuries could help in the identification of subjects with an increased risk for an ACL tear and to develop targeted prevention strategies, including education and training.

Racial differences in biochemical knee cartilage composition between African-American and Caucasian-American women with 3 T MR-based T2 relaxation time measurements--data from the Osteoarthritis Initiative.

OBJECTIVE: To determine whether knee cartilage composition differs between African-American and Caucasian-American women at risk for Osteoarthritis (OA) using in vivo 3 T MRI T2 relaxation time measurements. METHODS: Right knee MRI studies of 200 subjects (100 African-American women, and 100 closely matched Caucasian-American women) were selected from the Osteoarthritis Initiative (OAI). Knee cartilage was segmented in the patellar (PAT), medial and lateral femoral (MF/LF), and medial and lateral tibial compartments (MT/LT)). Mean T2 relaxation time values per compartment and per whole joint cartilage were generated and analyzed spatially via laminar and grey-level co-occurrence matrix (GLCM) texture methods. Presence and severity of cartilage lesions per compartment were graded using a modified WORMS grading. Statistical analysis employed paired t- and McNemar testing. RESULTS: While African-American women and Caucasian-Americans had similar WORMS cartilage lesion scores (P = 0.970), African-Americans showed significantly lower mean T2 values (∼1 ms difference; ∼0.5SD) than Caucasian-Americans in the whole knee cartilage (P < 0.001), and in the subcompartments (LF: P = 0.001, MF: P < 0.001, LT: P = 0.019, MT: P = 0.001) and particularly in the superficial cartilage layer (whole cartilage: P < 0.001, LF: P < 0.001, MF: P < 0.001, LT: P = 0.003, MT: P < 0.001). T2 texture parameters were also significantly lower in the whole joint cartilage of African-Americans than in Caucasian-Americans (variance: P = 0.001; contrast: P = 0.018). In analyses limited to matched pairs with no cartilage lesions in a given compartment, T2 values remained significantly lower in African-Americans. CONCLUSION: Using T2 relaxation time as a biomarker for the cartilage collagen network, our findings suggest racial differences in the biochemical knee cartilage composition between African-American and Caucasian-American women.

Relationship of unilateral total hip arthroplasty (THA) to contralateral and ipsilateral knee joint degeneration - a longitudinal 3T MRI study from the Osteoarthritis Initiative (OAI).

OBJECTIVE: To evaluate the association of prevalent unilateral total hip arthroplasty (THA) with worsening of degenerative knee abnormalities and clinical outcomes in the ipsilateral and contralateral knee. METHODS: Both knees of 30 individuals in the Osteoarthritis Initiative (OAI) with unilateral THA (n = 14 left, n = 16 right) at baseline were assessed at baseline and at 4-year follow-up for Whole-organ MR Imaging Scores (WORMS), cartilage T2 relaxation times (only available for right knees), Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores and upper leg isometric strength. Right knees of 30 individuals without THA were analyzed as controls. Contralateral knees were compared to ipsilateral knees with paired t-tests and to control knees with multivariate regression analysis adjusting for covariates. RESULTS: In paired analyses, compared to ipsilateral knees, contralateral knees had higher WORMS total (P = 0.008) and cartilage scores (P = 0.007) at baseline. Over 4 years contralateral knees worsened more on WORMS total score (P = 0.008). Cartilage T2 values were higher in knees contralateral to the THA (baseline, P = 0.02; follow-up, P < 0.001). Contralateral knees had greater declines in knee extension strength (P = 0.04) and had a trend for greater worsening in WOMAC pain, stiffness, function and total scores (P = 0.04-0.09). Similar results were found comparing contralateral knees with control knees in multivariate regression models. CONCLUSIONS: Prevalent unilateral THA is associated with an greater progression of degenerative findings for the knee contralateral to THA.

A reference database of cartilage 3 T MRI T2 values in knees without diagnostic evidence of cartilage degeneration: data from the osteoarthritis initiative.

OBJECTIVE: 1) To establish a gender- and BMI-specific reference database of cartilage T2 values, and 2) to assess the associations between cartilage T2 values and gender, age, and BMI in knees without radiographic osteoarthritis or MRI-based (WORMS 0/1) evidence of cartilage degeneration. DESIGN: 481 subjects aged 45-65 years with Kellgren-Lawrence Scores 0/1 in the study knee were selected. Baseline morphologic cartilage 3T MRI readings (WORMS scoring) and T2 measurements (resolution = 0.313 mm × 0.446 mm) were performed in the medial and lateral femurs, medial and lateral tibias, and patella compartments. To create a reference database, a logarithmic transformation was applied to the data to obtain the 5th-95th percentile values for T2. RESULTS: Significant differences in mean cartilage T2 values were observed between joint compartments. Although females had slightly higher T2 values than males in a majority of compartments, the differences were only significant in the medial femur (P < 0.0001). A weak positive association was seen between age and T2 in all compartments, most pronounced in the patella (3.27% increase in median T2/10 years, P = 0.009). Significant associations between BMI and T2 were observed, most pronounced in the lateral tibia (5.33% increase in median T2/5 kg/m(2) increase in BMI, P < 0.0001), and medial tibia (4.81% increase in median T2 /5 kg/m(2) increase in BMI, P < 0.0001). CONCLUSIONS: This study established the first reference database of T2 values in a large sample of morphologically normal cartilage plates in knees without radiographic knee osteoarthritis (OA). While cartilage T2 values were weakly associated with age and gender, they had the highest correlations with BMI.