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MRI-based cartilage compositional analysis shows biochemical and microstructural changes at early stages of osteoarthritis before changes become visible with structural MRI sequences and arthroscopy. This could help with early diagnosis, risk assessment, and treatment monitoring of osteoarthritis. Spin-lattice relaxation time constant in rotating frame (T1ρ) and T2 mapping are the MRI techniques best established for assessing cartilage composition. Only T2 mapping is currently commercially available, which is sensitive to water, collagen content, and orientation of collagen fibers, whereas T1ρ is more sensitive to proteoglycan content. Clinical application of cartilage compositional imaging is limited by high variability and suboptimal reproducibility of the biomarkers, which was the motivation for creating the Quantitative Imaging Biomarkers Alliance (QIBA) Profile for cartilage compositional imaging by the Musculoskeletal Biomarkers Committee of the QIBA. The profile aims at providing recommendations to improve reproducibility and to standardize cartilage compositional imaging. The QIBA Profile provides two complementary claims (summary statements of the technical performance of the quantitative imaging biomarkers that are being profiled) regarding the reproducibility of biomarkers. First, cartilage T1ρ and T2 values are measurable at 3.0-T MRI with a within-subject coefficient of variation of 4%-5%. Second, a measured increase or decrease in T1ρ and T2 of 14% or more indicates a minimum detectable change with 95% confidence. If only an increase in T1ρ and T2 values is expected (progressive cartilage degeneration), then an increase of 12% represents a minimum detectable change over time. The QIBA Profile provides recommendations for clinical researchers, clinicians, and industry scientists pertaining to image data acquisition, analysis, and interpretation and assessment procedures for T1ρ and T2 cartilage imaging and test-retest conformance. This special report aims to provide the rationale for the proposed claims, explain the content of the QIBA Profile, and highlight the future needs and developments for MRI-based cartilage compositional imaging for risk prediction, early diagnosis, and treatment monitoring of osteoarthritis., (© RSNA, 2021 See also the editorial by Kijowski in this issue.)

Background: Anterior cruciate ligaments (ACL) injuries represent a major risk factor for early osteoarthritis (OA)., Purpose: To evaluate the prevalence and 4-year progression of knee OA measured with 3T MR-imaging in individuals with ruptured, reconstructed or normal ACL and to assess the impact of thigh muscle characteristics., Methods: A total of 54 knees (23/54 male, 31/54 female) were recruited from the Osteoarthritis Initiative (OAI). At baseline, 15/54 subjects had prevalent ACL ruptures and 15/54 subjects had prevalent ACL reconstruction (24/54 normal ACL). Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores, Physical Activity Scores of the Elderly (PASE) and thigh muscle characteristics including strength, fat infiltration (Goutallier score) and thigh muscle cross-sectional area (CSA) MR measurements were obtained at baseline. Whole-organ MR-imaging Scores (WORMS) were obtained at baseline and at a 4-year follow-up time-point. Multivariate regression models, adjusting for covariates (age, gender, body mass index), were used for statistical analysis., Results: At baseline, subjects with prevalent ACL ruptures had worse WORMS total scores (mean±SEM, 44.1±3.5) than subjects with ACL reconstruction (30.8±4.0; P = 0.015) and worse than subjects with normal ACL (21.3±3.0; P<0.001). Cartilage scores were worse in both femorotibial compartments in ACL injured knees than in knees with normal ACL (P<0.05). Knees with ACL reconstruction showed an increased degeneration of the medial meniscus (P = 0.036), cartilage degeneration at the medial femoral condyle (P = 0.011). In a multivariate regression model, including both ACL groups and total muscle characteristics as influence parameters, high thigh muscle CSA, high muscle/ fat ratio and low Goutallier scores were associated with less degenerative changes at the knee, independent of ACL status. Knees with ACL reconstruction showed an increased progression of cartilage degeneration at the medial tibia compared to the normal ACL group (P = 0.027)., Conclusions: High thigh muscle CSA is associated with less degenerative changes at the knee, independent of the ACL status and may potentially be advantageous in the prevention of early OA., Competing Interests: The funding does not alter our adherence to PLOS ONE policies on sharing data and materials.

BackgroundObesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression.MethodsWe included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (

ObjectiveTo assess (i) the impact of changes in body weight on changes in joint-adjacent subcutaneous fat (SCF) and cartilage thickness over 4 years and (ii) the relation between changes in joint-adjacent SCF and knee cartilage thickness.DesignIndividuals from the Osteoarthritis Initiative (total=399) with > 10% weight gain (n=100) and > 10% weight loss (n=100) over 4 years were compared to a matched control cohort with less than 3% change in weight (n=199). 3.0T Magnetic Resonance Imaging (MRI) of the right knee was performed at baseline and after 4 years to quantify joint-adjacent SCF and cartilage thickness. Linear regression models were used to evaluate the associations between the (i) weight change group and 4-year changes in both knee SCF and cartilage thickness, and (ii) 4-year changes in knee SCF and in cartilage thickness. Analyses were adjusted for age, sex, baseline body mass index (BMI), tibial diameter (and weight change group in analysis (ii)).ResultsIndividuals who lost weight over 4-years had significantly less joint-adjacent SCF (beta range, medial/lateral joint sides: 2.2-4.2 mm, p

ObjectiveTo assess the effects of weight loss and weight gain on hip and knee radiographic changes, pain, and joint replacement over 4 years.MethodsParticipants (n = 2,752) from the Osteoarthritis Initiative were classified as those with weight gain (more than 5% gain), weight loss (more than -5% loss), or as controls (-3% to 3% change) over 4 years. Generalized estimating equations (adjusted for age, sex, and body mass index) were used to assess the relationship between the weight-change group and 4-year changes in knee radiographic osteoarthritis (OA) (Kellgren/Lawrence [K/L] grade), hip OA (Croft summary grade), joint space narrowing (JSN), and joint pain.ResultsFor radiographic knee OA, weight loss was associated with significantly lower odds of K/L grade worsening over 4 years (odds ratio [OR] 0.69 [95% confidence interval (95% CI) 0.53-0.91], P = 0.009), and weight gain was significantly associated with higher odds of medial knee JSN (OR 1.29 [95% CI 1.01-1.64], P = 0.038) compared to controls. For knee pain, weight loss was significantly associated with knee pain resolution over 4 years (OR 1.40 [95% CI 1.06-1.86], P = 0.019) while weight gain was associated with knee pain development (OR 1.34 [95% CI 1.08-1.67], P = 0.009) compared to controls. For all hip outcomes, no significant associations (P > 0.05) were found with weight-change groups. The associations between the weight-change group and total hip or total knee replacement were not significant (P > 0.05).ConclusionThis large, longitudinal study (n = 2,752 with 4-year follow-up) suggests that weight loss may protect against, and weight gain may exacerbate, radiographic and symptomatic knee OA, while weight change (at a 5% threshold) does not have significant effects on hip OA.

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.

BackgroundSynovial inflammation is a risk factor for osteoarthritis (OA). But to date, there is limited information on how inflammation impacts progression of knee OA.PurposeTo investigate how sustained synovitis, assessed with semi-quantitative magnetic resonance imaging (MRI) scores, impacts progression of knee degenerative changes over 4 years.Study typeRetrospective cohort study.SubjectsIn 249 participants (N = 132 women [53%]), from the Osteoarthritis Initiative (OAI) two definitions for synovitis were used resulting in two groups of participants with sustained synovitis at baseline, 2-year, and 4-year follow-up (N = 80 and N = 132), and two groups without synovitis at all three time points (N = 81 and N = 47).Field strength/sequence3 T intermediate-weighted (IW) turbo spin-echo (TSE) sequence and three-dimensional (3D) dual-echo steady-state (DESS) sequence.AssessmentSynovitis was scored semi-quantitatively using the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS), MRI Osteoarthritis Knee Score (MOAKS), and synovial proliferation score (SPS). Two MRI-based definitions of synovitis were used: (i) score ≥2 based on cumulative score of MOAKS and ACLOAS, and (ii) score ≥3 based on the cumulative score of ACLOAS, MOAKS, and SPS. Changes in structural abnormalities from baseline to year 4 measured using the whole-organ MRI score (WORMS) were defined as outcomes.Statistical testsLinear regression models were used to compare the differences in longitudinal changes in WORMS scores between participants with and without sustained synovitis for each definition of sustained synovitis. A P-value of

BackgroundTo assess the compound effects of BMI and sustained depressive symptoms on changes in knee structure, cartilage composition, and knee pain over 4 years using statistical interaction analyses.MethodsOne thousand eight hundred forty-four individuals from the Osteoarthritis Initiative Database were analyzed at baseline and 4-year follow-up. Individuals were categorized according to their BMI and presence of depressive symptoms (based on the Center for Epidemiological Studies Depression Scale (threshold≥16)) at baseline and 4-year follow-up. 3 T MRI was used to quantify knee cartilage T2 over 4 years, while radiographs were used to assess joint space narrowing (JSN). Mixed effects models examined the effect of BMI-depressive symptoms interactions on outcomes of cartilage T2, JSN, and knee pain over 4-years.ResultsThe BMI-depressive symptoms interaction was significantly associated with knee pain (p

OBJECTIVE: To qualitatively evaluate the utility of zero echo-time (ZTE) MRI sequences in identifying osseous findings and to compare ZTE with optimized spoiled gradient echo (SPGR) sequences in detecting knee osseous abnormalities. MATERIALS AND METHODS: ZTE and standard knee MRI sequences were acquired at 3T in 100 consecutive patients. Three radiologists rated confidence in evaluating osseous abnormalities and image quality on a 5-grade Likert scale in ZTE compared to standard sequences. In a subset of knees (n = 57) SPGR sequences were also obtained, and diagnostic confidence in identifying osseous structures was assessed, comparing ZTE and SPGR sequences. Statistical significance of using ZTE over SPGR was characterized with a paired t-test. RESULTS: Image quality of the ZTE sequences was rated high by all reviewers with 278 out of 299 (100 studies, 3 radiologists) scores ≥ 4 on the Likert scale. Diagnostic confidence in using ZTE sequences was rated very high confidence in 97%, 85%, 71%, and 73% of the cases for osteophytosis, subchondral cysts, fractures, and soft tissue calcifications/ossifications, respectively. In 74% of cases with osseous findings, reviewer scores indicated confidence levels (score ≥ 3) that ZTE sequences improved diagnostic certainty over standard sequences. The diagnostic confidence in using ZTE over SPGR sequences for osseous structures as well as abnormalities was favorable and statistically significant (p

ObjectiveTo assess differences in biochemical composition of the deep cartilage layer in subjects with type 2 diabetes mellitus (T2DM) and nondiabetic controls using UTE (ultra-short echo time) T2* mapping and to investigate the association of vascular health and UTE T2* measurements.DesignTen subjects with T2DM matched for age, sex, and body mass index with 10 nondiabetic controls. A 3D UTE sequence with 6 echo times was acquired using 3T magnetic resonance imaging of the knee. For UTE T2* analysis, the deep cartilage layer was segmented and analyzed in 5 compartments (patella, medial, and lateral femur and tibia). The ankle brachial index (ABI) was obtained in all subjects. Linear regression analyses were used to assess associations of T2DM and UTE T2* relaxation times and the associations of ABI measurements and UTE measurements.ResultsCompared with nondiabetic controls, T2DM subjects had significantly lower mean T2*-UTE in the patella (mean difference 4.87 ms; 95% confidence interval [CI] 1.09-8.65; P = 0.015), the lateral tibia (mean difference 2.26 ms; 95% CI 0.06-4.45; P = 0.045), and the lateral femur (mean difference 4.96 ms; 95% CI 0.19-9.73; P = 0.043). Independent of diabetic status, subjects with higher ABI values, indicating better vascular health, had higher T2*-UTE of the patella (coefficient 15.2; 95% CI 3.3-21.4; P = 0.017), the medial tibia (coefficient 9.8; 95% CI 1.0-18.6; P = 0.031), and the lateral femur (coefficient 18.8; 95% CI 3.3-34.3; P = 0.021).ConclusionsT2*-UTE measurements of the deep cartilage layer were consistently lower in subjects with T2DM and in subjects with impaired vascular health, likely indicating increased mineralization of this layer.

BackgroundOpioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years.MethodsParticipants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0-96) and subscores for cartilage (0-36), menisci (0-24), and bone marrow abnormalities and subchondral cyst-like lesions (0-18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0-100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade.ResultsOpioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8],

ObjectiveTo identify joint structural risk factors, measured using quantitative compositional and semiquantitative magnetic resonance imaging (MRI) scoring, associated with the development of accelerated knee osteoarthritis (AKOA) compared with a more normal rate of knee osteoarthritis (OA) development.DesignFrom the Osteoarthritis Initiative we selected knees with no radiographic OA (Kellgren-Lawrence grade [KL] 0/1) that developed advanced-stage OA (KL 3/4; AKOA) within a 4-year timeframe and a comparison group with a more normal rate of OA development (KL 0/1 to KL 2 in 4 years). MRIs at the beginning of the 4-year timeframe were assessed for cartilage T2 values and structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of MRI findings with AKOA versus normal OA were assessed using multivariable logistic regression models.ResultsA total of 106 AKOA and 168 subjects with normal OA development were included. Mean cartilage T2 values were not significantly associated with AKOA (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.82-1.36). Risk factors for AKOA development included higher meniscus maximum scores (OR 1.37; 95% CI 1.11-1.68), presence of meniscal extrusion (OR 6.30; 95% CI 2.57-15.49), presence of root tears (OR 4.64; 95% CI 1.61-13.34), and higher medial tibia cartilage lesion scores (OR 1.96; 95% CI 1.19-3.24).ConclusionsWe identified meniscal damage, especially meniscal extrusion and meniscal root tears as risk factors for AKOA development. These findings contribute to identifying subjects at risk of AKOA at an early stage when preventative measures targeting modifiable risk factors such as meniscal repair surgery could still be effective.

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 T 1ρ and T 2 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 T 1ρ and T 2 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 T 1ρ , while MFPC 2 and BMI were related to T 2 relaxation times. In the acetabular cartilage, sagittal plane MFPC 1 and BMI were related to T 1ρ , while BMI was related to T 2 relaxation times. Greater internal rotation was related to increased T 1ρ and T 2 relaxation times in the femoral cartilage, while the greater extension was related to increased T 1ρ 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.

ObjectiveTo evaluate the association of fatty infiltration of the quadriceps and vastus medialis (VM) with an increase in knee cartilage, meniscus, or bone marrow lesions, using magnetic resonance imaging (MRI) in knee osteoarthritis (OA) over 3 years.MethodsParticipants (n = 69) with and without radiographic knee OA underwent MRI at baseline and 3 years later. Chemical shift-based water/fat MRI was used to quantify the intramuscular fat fraction and the lean anatomical cross-sectional area (ACSA) for the VM and entire quadriceps muscles. MRI images of the knee were analyzed using the semiquantitative modified whole-organ MRI score (mWORMS) grading to assess change in lesions in the articular cartilage, meniscus, and bone marrow. Logistic regression was used to assess whether baseline quadriceps and VM fat fraction and lean ACSA were associated with an increase in mWORMS scores. Odds ratios (ORs) were adjusted for age, sex, and body mass index.ResultsOverall, of the 69 subjects, 43 (62%) had an increase in cartilage lesions (26 of 43), meniscus lesions (19 of 43), or bone marrow lesions (22 of 43) scores. The quadriceps (OR 2.13 [95% confidence interval (95% CI) 1.09-4.15]) and VM (OR 2.05 [95% CI 1.25-3.36]) fat fraction were both associated with an increase in cartilage, meniscus, or bone marrow lesion scores over 3 years. The association of quadriceps or VM lean ACSA with the outcomes was not significant.ConclusionThese longitudinal findings using quantitative MRI methods for assessment of muscle adiposity highlight the role of quadriceps adiposity, specifically in the VM, in knee OA progression. However, studies in larger cohorts are needed to confirm these findings.

BackgroundAdipose tissue has recently gained interest as an independent imaging biomarker for osteoarthritis.PurposeTo explore 1) cross-sectional associations between local subcutaneous fat (SCF) thickness at the knee and the extent of degenerative changes in overweight and obese individuals and 2) associations between local fat distribution and progression of osteoarthritis over 4 years.Study typeRetrospective cohort study.Population338 obese and overweight participants from the Osteoarthritis Initiative cohort without radiographic evidence of osteoarthritis.Field strength3T: 3D-FLASH-WE; 3D-DESS-WE; T1w-SE; MSME.AssessmentBaseline SCF thickness was measured in standardized locations medial, lateral and anterior to the knee and the average joint-adjacent SCF (ajSCF) was calculated. Right thigh SCF cross-sectional area was assessed. Quantitative cartilage T2 relaxation times and semi-quantitative whole organ MRI scores (WORMS) were obtained at baseline and 4-year follow-up. WORMSsum was calculated as sum of cartilage, bone marrow edema, subchondral cyst, and meniscal scores.Statistical testsAssociations of SCF measures with baseline, and 4-year change in T2 and WORMS were analyzed using regression models. SCF measurements were standardized using the equation ValueParticipant-MeanCohortStandard deviation . Analyses were adjusted for age, sex, physical activity, and BMI.ResultsCross-sectionally, significant associations between lateral SCF, lateral compartment WORMS and T2 were found ( ΔWORMSsum1SDchange in lateralSCF , [95% CI]: 0.53, [0.12-0.95], P

BACKGROUND. The extent of medial meniscal extrusion (MME) that is associated with structural and symptomatic progression of knee osteoarthritis has not been defined yet. OBJECTIVE. The purpose of our study was to investigate MRI-based thresholds of MME that are associated with structural progression of knee degenerative disease and symptoms over a period of 4 years. METHODS. We studied 328 knees of 235 participants that were randomly selected from the Osteoarthritis Initiative cohort. MME was quantified on coronal sections of intermediate-weighted MRI sequences obtained at 3 T. Knee pain and cartilage abnormalities were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and the cartilage whole-organ MRI score (WORMS). General estimating equations with logistic regression models were used to correlate baseline MME and changes in pain (WOMAC) and cartilage damage (WORMS). ROC analyses were performed to determine the area under the ROC curve (AUROC). Individual thresholds were determined by maximizing the product of sensitivity and specificity. RESULTS. The AUROC for predicting progression of knee pain, medial compartment cartilage damage, and medial tibial cartilage damage were 0.71, 0.70, and 0.72, respectively, and the individual thresholds for MME were 2.5, 2.7, and 2.8 mm. A single threshold of 2.5 mm was determined by maximizing the mean of the product of sensitivity and specificity of the three outcome variables (knee pain progression, medial compartmental cartilage damage progression, and medial tibial cartilage damage progression). CONCLUSION. MME was associated with knee pain and cartilage damage progression over 4 years. A single threshold of 2.5 mm was found to be the most useful threshold for predicting knee pain, medial compartment cartilage damage progression, and tibial cartilage damage progression over 4 years. CLINICAL IMPACT. This threshold could be used to standardize the diagnostic criterion of extrusion and to better characterize the risk for subsequent structural and symptomatic progression of knee osteoarthritis.

ObjectiveThe aim of this study was to investigate the associations between weight cycling and knee joint degeneration in individuals with overweight or obesity with different patterns of weight change over 4 years.MethodsA total of 2,271 individuals from the Osteoarthritis Initiative database were assessed (case-control study). Linear regression models using annual BMI measurements over 4 years were used to classify participants as weight cyclers or noncyclers. 3-T magnetic resonance imaging was used to quantify knee cartilage transverse relaxation time (T2) and cartilage thickness annually over 4 years in all subjects. Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone-marrow abnormalities in 958 subjects at baseline and at the 4-year follow-up. The longitudinal differences in cartilage T2 and thickness between weight cyclers and noncyclers were assessed using general estimating equations, whereas the differences in WORMS outcomes were compared using general linear models.ResultsNo significant differences in the rate of change of cartilage thickness or T2 were found between weight cyclers and noncyclers. However, increases in maximum cartilage WORMS (P = 0.0025) and bone-marrow abnormalities (P = 0.04) were significantly greater in weight cyclers than in noncyclers.ConclusionsAlthough participants' intent for weight cycling in this study was unknown, weight cyclers had significantly greater increases in cartilage and bone-marrow abnormalities over 4 years than noncyclers, independent of weight gain and loss.

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.

BackgroundOsteoarthritis (OA) is a degenerative joint disease. Understanding contributing factors to slowing or stopping disease progression is crucial. There has been no research describing lower extremity kinematics of the hip, knee, and ankle during stair ambulation in individuals with hip OA.ObjectiveTo explore the differences in lower extremity kinematics between participants with clinical and morphological findings of hip OA and controls.DesignA cross-sectional study.SettingClinical research laboratory.ParticipantsParticipants with radiographic and symptomatic signs of hip OA (n = 42) and healthy controls (n = 30) were enrolled.InterventionsParticipants underwent hip magnetic resonance imaging (MRI). The Scoring Hip Osteoarthritis with MRI (SHOMRI) method was used to assess cartilage abnormalities. Self-reported measures of hip pain and function were obtained using the Hip Disability and Osteoarthritis Outcome Score (HOOS). Participants were assigned into a symptomatic hip osteoarthritis group (HOA) with SHOMRI>0 and HOOS≤80, and a control group (CG) with SHOMRI = 0 and HOOS>90. Patients underwent 3D motion analysis during stair ascent/descent at self-selected speed.Main outcome measuresThe primary outcome measurements were peak hip, knee, and ankle kinematics. General Estimation Equations were used to compare kinematics between groups (P ≤ .05).ResultsThe HOA group ascended stairs with a more internally rotated hip (CG = 1.77 ± 6.3; HOA = 4.97 ± 4.2; P = .02), more abducted hip (CG = -5 ± 2.7, HOA = -3.5 ± 3; P = .02), and a more externally rotated knee (CG = -8.02 ± 3; HOA = -10.63 ± 6.3; P = .02) and ankle (CG = -11.8 ± 6.1; HOA = -16.3 ± 5.6; P = .01). Similarly, HOA participants descended stairs with a more extended knee (CG = -15.5 ± 4.9; HOA = -12 ± 4.9; P = .01), and more externally rotated knee (CG = -10.1 ± 4.4; HOA = -13.1 ± 6.6; P = .04) and ankle (CG = -13.5 ± 5.3; HOA = -17.9 ± 5.5; P = .002).ConclusionParticipants with hip OA-related morphology and symptoms ambulate stairs utilizing abnormal lower extremity mechanics.

ObjectiveThis work aims to study (i) the relationship between body mass index (BMI) and knee synovial inflammation using non-contrast-enhanced MRI and (ii) the association of synovial inflammation versus degenerative abnormalities and pain.Materials and methodsSubjects with risk for and mild to moderate radiographic osteoarthritis were selected from the Osteoarthritis Initiative. Subjects were grouped into three BMI categories with 87 subjects per group: normal weight (BMI, 20-24.9 kg/m2), overweight (BMI, 25-29.9 kg/m2), and obese (BMI, ≥ 30 kg/m2), frequency matched for age, sex, race, Kellgren-Lawrence grade, and history of knee surgery and injury. Semi-quantitative synovial inflammation imaging biomarkers were obtained including effusion-synovitis, size and intensity of infrapatellar fat pad signal abnormality, and synovial proliferation score. Cartilage composition was measured using T2 relaxation time and structural abnormalities using the whole-organ magnetic resonance imaging score (WORMS). The Western Ontario and McMasters (WOMAC) Osteoarthritis Index was used for pain assessment. Intra- and inter-reader reproducibility was assessed by kappa values.ResultsOverweight and obese groups had higher prevalence and severity of all synovial inflammatory markers (p ≤ 0.03). Positive associations were found between synovial inflammation imaging biomarkers and average T2 values, WORMS maximum scores and total WOMAC pain scores (p

ObjectivesTo study the natural history of new horizontal meniscal tears and their association with progression of cartilage degeneration in individuals at risk for or with mild to moderate knee osteoarthritis over 4 years.MethodsIndividuals who developed a new meniscal tear in the right knee over 2 years were selected from the Osteoarthritis Initiative 3T MRI studies. Knee structural changes were analyzed at the time of tear appearance (baseline), and after 4 years using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Meniscal tears were classified as either horizontal tears or non-horizontal tears. Individuals without a meniscal tear were 1:3 frequency matched according to BMI, gender, race, and age and served as the control group. Linear regression analysis was used to compare cross-sectional and longitudinal changes in cartilage WORMS scores.ResultsForty-one subjects developed horizontal tears, including one indiviudal who developed a tear in both menisci, and 34 developed non-horizonal tears. We found that (29/41 (70.7%)) of horizontal and (20/34 (58.8%)) of non-horizonatal tears were stable during follow-up (p = 0.281). Although knees with an incident tear had higher than controls WORMS MAX total knee scores at baseline (coef. = 0.47, p = 0.044, 95% CI = 0.01 to 0.93), there were no significant differences between the horizontal subgroup and knees without tears in overall cartilage scores at baseline and in progression over 4 years of follow-up.ConclusionsNew horizontal meniscal tears tended to be stable over 4 years and presented no significant differences in progression of cartilage degeneration when compared with knees without tears.Key points• Most of horizonal meniscal tears were stable over 4 years. • There were no statistically significant differences in overall progression of cartilage degenerative changes between knees with horizonal meniscal tears and control knees without tears • Horizontal tears most often occurred at the posterior horn of the medial meniscus and at the body of the lateral meniscus.

ObjectiveTo investigate the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with changes in knee cartilage composition and joint structure over 48 months, using magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative (OAI).Materials and methodsA total of 1126 participants with right knee Kellgren-Lawrence (KL) score 0-2 at baseline, no history of rheumatoid arthritis, blood pressure measurements at baseline, and cartilage T2 measurements at baseline and 48 months were selected from the OAI. Cartilage composition was assessed using MRI T2 measurements, including laminar and gray-level co-occurrence matrix texture analyses. Structural knee abnormalities were graded using the whole-organ magnetic resonance imaging score (WORMS). We performed linear regression, adjusting for age, sex, body mass index, physical activity, smoking status, alcohol use, KL score, number of anti-hypertensive medications, and number of nonsteroidal anti-inflammatory drugs.ResultsHigher baseline DBP was associated with greater increases in global T2 (coefficient 0.22 (95% CI 0.09, 0.34), P = 0.004), global superficial layer T2 (coefficient 0.39 (95% CI 0.20, 0.58), P = 0.001), global contrast (coefficient 15.67 (95% CI 8.81, 22.53), P

ObjectiveTo determine the cross-sectional and longitudinal associations of vitamin C and D intake with magnetic resonance imaging (MRI) measures of cartilage composition (T2) and joint structure (cartilage, meniscus, and bone marrow) using data from the Osteoarthritis Initiative (OAI) cohort.MethodsA total of 1,785 subjects with radiographic Kellgren/Lawrence knee grades 0-3 in the right knee were selected from the OAI database. Vitamins C and vitamin D intake (diet, supplements, and total) were assessed using the Block Brief 2000 Food Frequency Questionnaire at baseline. The MRI analysis protocol included 3T cartilage T2 quantification and semiquantitative joint morphology gradings (Whole-Organ Magnetic Resonance Imaging Score [WORMS]) at baseline and 4 years. Linear regression was used to assess the association between standardized baseline vitamin intake and both baseline WORMS scores and standardized cartilage T2 values.ResultsHigher vitamin C intake was associated with lower average cartilage T2 values, medial tibia T2 values, and medial tibia WORMS scores (standardized coefficient range -0.07 to -0.05, P < 0.05). Higher vitamin D intake was associated with a lower cartilage WORMS sum score and medial femur WORMS score (standardized coefficient range -0.24 to -0.09, P < 0.05). Consistent use of vitamin D supplements of 400 IU at least once a week over 4 years was associated with significantly less worsening of cartilage, meniscus, and bone marrow abnormalities (odds ratio range 0.40-0.56, P < 0.05).ConclusionSupplementation with vitamin D over 4 years was associated with significantly less progression of knee joint abnormalities. Given the observational nature of this study, future longitudinal randomized controlled trials of vitamin D supplementation are warranted.

ObjectiveTo identify joint structural risk factors, measured using quantitative compositional and semiquantitative magnetic resonance imaging (MRI) scoring, associated with the development of accelerated knee osteoarthritis (AKOA) compared with a more normal rate of knee osteoarthritis (OA) development.DesignFrom the Osteoarthritis Initiative we selected knees with no radiographic OA (Kellgren-Lawrence grade [KL] 0/1) that developed advanced-stage OA (KL 3/4; AKOA) within a 4-year timeframe and a comparison group with a more normal rate of OA development (KL 0/1 to KL 2 in 4 years). MRIs at the beginning of the 4-year timeframe were assessed for cartilage T2 values and structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of MRI findings with AKOA versus normal OA were assessed using multivariable logistic regression models.ResultsA total of 106 AKOA and 168 subjects with normal OA development were included. Mean cartilage T2 values were not significantly associated with AKOA (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.82-1.36). Risk factors for AKOA development included higher meniscus maximum scores (OR 1.37; 95% CI 1.11-1.68), presence of meniscal extrusion (OR 6.30; 95% CI 2.57-15.49), presence of root tears (OR 4.64; 95% CI 1.61-13.34), and higher medial tibia cartilage lesion scores (OR 1.96; 95% CI 1.19-3.24).ConclusionsWe identified meniscal damage, especially meniscal extrusion and meniscal root tears as risk factors for AKOA development. These findings contribute to identifying subjects at risk of AKOA at an early stage when preventative measures targeting modifiable risk factors such as meniscal repair surgery could still be effective.

BackgroundMRI-based relaxation time measurements provide quantitative assessment of cartilage biochemistry. Identifying distinctive relaxometry features in hip osteoarthritis (OA) might provide important information on regional disease variability.PurposeFirst, to incorporate fully automatic voxel-based relaxometry (VBR) with principal component analysis (PCA) to extract distinctive relaxometry features in subjects with radiographic hip OA and nondiseased controls. Second, to use the identified features to further distinguish subjects with cartilage compositional abnormalities.Study typeCross-sectional.SubjectsThirty-three subjects with radiographic hip OA (20 males; age, 50.2 ± 13.3 years) and 55 controls participated (28 males; 41.3 ± 12.0 years).SequenceA 3.0T scanner using 3D SPGR, combined T1ρ /T2 , and fast spin echo sequences.AssessmentPelvic radiographs, patients' self-reported symptoms, physical function, and cartilage morphology were analyzed. Cartilage relaxation times were quantified using traditional regions of interest and VBR approaches. PCA was performed on VBR data to identify distinctive relaxometry features, and were subsequently used to identify a subgroup of subjects from the controls that exhibited compositional abnormalities.Statistical testsChi-square and independent t-tests were used to compare group characteristics. Logistic regression models were used to identify the possible principal components (PCs) that were able to predict OA vs. control classification.ResultsIn T1ρ assessment, OA subjects demonstrated higher T1ρ values in the posterior hip region and deep cartilage layer when compared with controls (P = 0.012 and 0.001, respectively). In T2 assessment, OA subjects exhibited higher T2 values in the posterior hip region (P

ObjectiveTo compare the extent of cartilage deterioration in knees with prior meniscal resection related to trauma versus knees with resection related to degenerative disease, and to compare cartilage deterioration in knees with meniscal surgery to knees without meniscal surgery, controlling for prior knee trauma.Materials and methodsIn this cross-sectional study, we assessed cartilage deterioration in right knees of Osteoarthritis Initiative participants: (i) with meniscal surgery due to injury (n = 79); (ii) matched control knees with a prior injury but without meniscal surgery (n = 79); (iii) with meniscal surgery but without preceding injury (n = 36); and (iv) matched control knees without meniscal surgery or prior knee injury (n = 36). Cartilage composition was measured using T2 measurements derived using semi-automatic cartilage segmentation of the right. Linear regression analysis was used to compare compartmental values of T2 between groups.ResultsComparing the mean T2 values in surgical cases with and without injury our results did not show significant differences (group i vs. iii, p > 0.05). However, knees with previous meniscal surgery showed significantly (p

ObjectiveTo analyze structural, longitudinal MRI findings during the development of accelerated knee osteoarthritis (AKOA) over 4 years.Materials and methodsFrom the Osteoarthritis Initiative (OAI), knees with no radiographic osteoarthritis (KL 0/1) developing advanced-stage osteoarthritis (KL 3/4; AKOA) within a 4-year (y) timeframe were selected. MRIs were graded using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) at the beginning of the 4-year timeframe (index visit), at 2-year, and 4-year follow-up. Morphological and clinical findings associated with KL 3/4 onset within 2 years compared to 4 years were assessed using generalized estimating equations.ResultsAKOA was found in 162 knees of 149 subjects (age 63.25 ± 8.3; 103 females; BMI 29.4 ± 3.9). Moderate to severe meniscal lesions WORMS ≥ 3 were present in 25% (41/162) at the index visit, 64% (104/162) at 2-year and 93% (151/162) at 4-year follow-up. Meniscal extrusion was the most prevalent finding (ranging from 18% at the index visit, 45% at 2-year and 94% at 4-year follow-up) and root tears were the most common types of tears (9% at the index visit; 22% at 2 years and 38% at 4 years). Risk factors associated with KL 3/4 onset within 2 years included root tears at the index visit (adjusted OR, 2.82; 95% CI: 1.33, 6.00; p = 0.007) and incident knee injury (42%, 49/116 vs. 24%, 11/46, p = 0.032).ConclusionsMeniscal abnormalities, in particular extrusion and root tears, were the most prevalent morphological features found in subjects with AKOA. These results suggest that meniscal abnormalities have a significant role in accelerated progression of OA.

BackgroundMetabolic disorders presenting in HIV-infected patients on antiretroviral therapy (ART) may increase the risk of osteoarthritis. However, structural changes of the knee in HIV infected subjects are understudied. The aim of this study is to investigate knee cartilage degeneration and knee structural changes over 8 years in subjects with and without HIV infection determined based on the use of ART.MethodsWe studied 10 participants from the Osteoarthritis Initiative who received ART at baseline and 20 controls without ART, frequency matched for age, sex, race, baseline body mass index (BMI) and Kellgren & Lawrence grade. Knee abnormalities were assessed using the whole-organ magnetic resonance imaging score (WORMS) and cartilage T2 including laminar and texture analyses were analyzed using a multislice-multiecho spin-echo sequence. Signal abnormalities of the infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) were assessed separately using a semi-quantitative scoring system. Linear regression models were used in the cross-sectional analysis to compare the differences between ART/HIV subjects and controls in T2 (regular and laminar T2 values, texture parameters) and morphologic parameters (subscores of WORMS, scores for signal alterations of IPFP and SPFP). Mixed effects models were used in the longitudinal analysis to compare the rate of change in T2 and morphological parameters between groups over 8 years.ResultsAt baseline, individuals on ART had significantly greater size of IPFP signal abnormalities (P = 0.008), higher signal intensities of SPFP (P = 0.015), higher effusion scores (P = 0.009), and lower subchondral cysts sum scores (P = 0.003) compared to the controls. No significant differences were found between the groups in T2-based cartilage parameters and WORMS scores for cartilage, meniscus, bone marrow edema patterns and ligaments (P > 0.05). Longitudinally, the HIV cohort had significantly higher global knee T2 entropy values (P = 0.047), more severe effusion (P = 0.001) but less severe subchondral cysts (P = 0.002) on average over 8 years.ConclusionsKnees of individuals with HIV on ART had a more heterogeneous cartilage matrix, more severe synovitis and abnormalities of the IPFP and SPFP, which may increase the risk of incident knee osteoarthritis.

ObjectiveTo investigate the natural history of central osteophytes (COs) by analyzing the structure and matrix composition of CO-associated cartilage using 3-T MRI at and 1-3 years before the onset of COs.Materials and methodsBaseline, 4- and 6-year knee MRIs of 400 participants in the Osteoarthritis Initiative were screened for the appearance of new COs. Twenty-eight subjects developed 31 COs. Using MRIs at CO onset and 1-3 years before CO onset, cartilage T2 values were calculated for the local cartilage preceding COs and the surrounding cartilage. Cartilage lesions local to the site of COs and bone marrow edema like lesions (BMELs) subjacent to COs were graded using whole organ MRI scores (WORMS). Wilcoxon tests were used to compare T2 values from the local and the surrounding cartilage at each time point and to compare T2 and WORMS between time points. Knee symptoms were recorded during this period.ResultsAll subjects showed local cartilage lesions before the development of COs. Mean cartilage WORMS increased from 1.56 ± 0.66 a period of 3 years before to 2.39 ± 0.75 with onset of COs (p = 0.008). Local T2 values in the area of the later-appearing COs were significantly higher compared with T2 values of the surrounding cartilage 3 (p = 0.044) and 2 years earlier (p = 0.031) and with the onset of COs (p = 0.025). No significant increase in symptoms was found with the onset of COs.ConclusionThis study provides evidence that focal cartilage structural and compositional degeneration precedes COs. No significant aggravation of knee symptoms was reported during the evolution of COs.

Osteoarthritis (OA) classification in the knee is most commonly done with radiographs using the 0-4 Kellgren Lawrence (KL) grading system where 0 is normal, 1 shows doubtful signs of OA, 2 is mild OA, 3 is moderate OA, and 4 is severe OA. KL grading is widely used for clinical assessment and diagnosis of OA, usually on a high volume of radiographs, making its automation highly relevant. We propose a fully automated algorithm for the detection of OA using KL gradings with a state-of-the-art neural network. Four thousand four hundred ninety bilateral PA fixed-flexion knee radiographs were collected from the Osteoarthritis Initiative dataset (age = 61.2 ± 9.2 years, BMI = 32.8 ± 15.9 kg/m2, 42/58 male/female split) for six different time points. The left and right knee joints were localized using a U-net model. These localized images were used to train an ensemble of DenseNet neural network architectures for the prediction of OA severity. This ensemble of DenseNets' testing sensitivity rates of no OA, mild, moderate, and severe OA were 83.7, 70.2, 68.9, and 86.0% respectively. The corresponding specificity rates were 86.1, 83.8, 97.1, and 99.1%. Using saliency maps, we confirmed that the neural networks producing these results were in fact selecting the correct osteoarthritic features used in detection. These results suggest the use of our automatic classifier to assist radiologists in making more accurate and precise diagnosis with the increasing volume of radiographic image being taken in clinic.

ObjectivesTo develop an MR-based semi-quantitative meniscus scoring technique for postoperative assessment of the degree of meniscal resection, to test its reproducibility, and to study the relationship between the amount of resection and degenerative disease burden.MethodsWe studied the right knee of 135 participants from the Osteoarthritis Initiative that underwent meniscal surgery an average of 14 years previously. The amount of meniscal resection was assessed on baseline 3.0-T MRIs and calculated as meniscus resection score (MenRS) with a range of 0 to 18. Knee abnormalities at baseline and 48 months were graded using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Subjects were also stratified according to meniscal resection performed after injury versus without preceding injury. Statistical analysis included intra-class correlation coefficient (ICC) to determine reproducibility as well as regression models and partial correlations to correlate MenRS with WORMS outcomes.ResultsICC values for intra- and inter-observer reproducibility of MenRS were 0.980 and 0.977, respectively. Overall, the amount of meniscal resection showed a significant correlation with baseline WORMS grades: higher MenRS was associated with higher total WORMS grades (p = 0.004) and cartilage (p = 0.004) and ligament (p

BackgroundSemiquantitative assessment of MRI plays a central role in musculoskeletal research; however, in the clinical setting MRI reports often tend to be subjective and qualitative. Grading schemes utilized in research are not used because they are extraordinarily time-consuming and unfeasible in clinical practice.PurposeTo evaluate the ability of deep-learning models to detect and stage severity of meniscus and patellofemoral cartilage lesions in osteoarthritis and anterior cruciate ligament (ACL) subjects.Study typeRetrospective study aimed to evaluate a technical development.PopulationIn all, 1478 MRI studies, including subjects at various stages of osteoarthritis and after ACL injury and reconstruction.Field strength/sequence3T MRI, 3D FSE CUBE.AssessmentAutomatic segmentation of cartilage and meniscus using 2D U-Net, automatic detection, and severity staging of meniscus and cartilage lesion with a 3D convolutional neural network (3D-CNN).Statistical testsReceiver operating characteristic (ROC) curve, specificity and sensitivity, and class accuracy.ResultsSensitivity of 89.81% and specificity of 81.98% for meniscus lesion detection and sensitivity of 80.0% and specificity of 80.27% for cartilage were achieved. The best performances for staging lesion severity were obtained by including demographics factors, achieving accuracies of 80.74%, 78.02%, and 75.00% for normal, small, and complex large lesions, respectively.Data conclusionIn this study we provide a proof of concept of a fully automated deep-learning pipeline that can identify the presence of meniscal and patellar cartilage lesions. This pipeline has also shown potential in making more in-depth examinations of lesion subjects for multiclass prediction and severity staging.Level of evidence2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:400-410.

BackgroundThis study aimed to utilize voxel-based relaxometry (VBR) to examine local correlations between patellofemoral joint (PFJ) stress during gait and PFJ cartilage relaxation times.MethodsEighty-three subjects with and without PFJ osteoarthritis (OA) underwent knee magnetic resonance (MR) images using fast spin-echo, T1ρ and T2 relaxation time sequences. Patellar and trochlear cartilage relaxation times were computed for each voxel. Peak PFJ stress was computed during the stance phase from three-dimensional gait analysis. Statistical Parametric Mapping was used to perform VBR analyses. Pearson partial correlations were used to evaluate the associations between peak PFJ stress and cartilage relaxation times while controlling for age, sex, and body mass index.ResultsA higher percentage of the trochlear cartilage (15.9-29.1%) showed significant positive correlations between PFJ stress and T1ρ and T2 than the patellar cartilage (7.4-13.6%). Average correlation coefficient (R) of the voxels showing significant positive correlations ranged from 0.27 to 0.29. Subcompartment analysis revealed a higher percentage of lateral compartment cartilage (trochlea: 30.2-34.7%, patella: 8.1-14.8%) showed significant correlations between peak PFJ stress and T1ρ and T2 than the medial compartment cartilage (trochlea: 7.1-27.2%, patella: 5.5-5.9%). Subgroup analysis showed that larger percentages of PFJ cartilage demonstrated significant positive correlations with PFJ stress in subjects with PFJ OA than those without PFJ OA.ConclusionsThe findings of this study suggest that peak PFJ stress has a greater influence on the biochemical composition of the trochlear than the patellar cartilage, and the lateral than the medial PFJ compartment.

BackgroundOsteoarthritis (OA), a multifactorial disease causing joint degeneration, often leads to severe disability. The rising rates of disability highlight the need for implementing preventative measures at early stages of the disease, which would especially benefit subjects at high risk for OA development.PurposeTo develop a risk prediction tool for moderate-severe OA (TOARP) over 8 years based on subject characteristics, knee radiographs, and MRI data at baseline using data from the Osteoarthritis Initiative (OAI).Study typeRetrospective.Subjects641 subjects with no/mild radiographic OA (Kellgren-Lawrence [KL] 0-2) and no clinically significant symptoms (Western Ontario and McMaster Universities Arthritis Index [WOMAC] 0-1) were selected from the OAI.Field strength/sequenceMR images were obtained using 3.0T.AssessmentCompartment-specific cartilage and meniscus morphology and cartilage T2 were assessed. Baseline subject demographics, risk factors, KL score, cartilage WORMS score, presence of meniscus tear, and cartilage T2 were used to predict the development of moderate/severe OA (KL = 3-4 or WOMAC pain ≥5 or total knee replacement [TKR]) over 8 years.Statistical testsBest subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA.ResultsModel 1 included KL score, previous knee injury in the last 12 months, age, gender, and BMI. Model 2 included all variables in Model 1 plus presence of cartilage defects in the lateral femur and patella, and presence of a meniscal tear. Model 3 included all variables in Models 1 and 2, plus cartilage T2 in the medial tibia and medial femur. Compared to Model 1 (cross-validated AUC = 0.67), Model 3 performed significantly better (AUC = 0.72, P = 0.04), while Model 2 showed a statistical trend (AUC = 0.71, P = 0.08).Data conclusionWe established a risk calculator for the development of moderate/severe knee OA over 8 years that includes radiographic and MRI data. The inclusion of MRI-based morphological abnormalities and cartilage T2 significantly improved model performance.Level of evidence2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526.

ObjectiveTo analyze associations of suprapatellar fat pad (SPFP) hyperintense signal alterations and mass effect with progression of patellofemoral osteoarthritis (OA) and clinical symptoms over 48 months.Materials and methodsSubjects from the Osteoarthritis Initiative (n = 426; 51.8 ± 3.8 years; 49.8% women) without radiographic tibiofemoral OA underwent 3T-MRI of their right knees and clinical evaluation using the Knee Injury and Osteoarthritis Outcome Score at baseline and at 48 months. Elevated SPFP signal was assessed on intermediate-weighted, fat-saturated turbo spin-echo (TSE) images. Mass effect was defined as a convex posterior contour. Patellofemoral cartilage, bone marrow lesions (BML), and subchondral cysts were assessed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of SPFP imaging findings with MRI and clinical progression were assessed using general linear models and logistic regressions.ResultsBaseline SPFP signal alterations were found in 51% of the subjects (n = 217), of whom 11% (n = 23) additionally had a mass effect. Progression of cartilage lesions was significantly higher in subjects with signal alteration versus without (adjusted mean increases, 95% CI; patella: 0.29, -0.07 to 0.64 vs -0.04, -0.40 to 0.31; p  0.18 for all).ConclusionPatellofemoral joint degeneration over 48 months was significantly increased in subjects with SPFP signal alteration, suggesting an association between SPFP abnormalities and the progression of patellofemoral OA.

PurposeTo investigate the association of the presence and severity of diabetes mellitus (DM) with articular cartilage composition, using magnetic resonance imaging (MRI)-based T2 relaxation time measurements, and structural knee abnormalities.Materials and methodsIn the Osteoarthritis Initiative 208, participants with DM (age 63.0 ± 8.9 years; 111 females) and risk factors for osteoarthritis (OA) or mild radiographic tibiofemoral OA (Kellgren-Lawrence [KL] grade ≤2) were identified and group-matched with 208 controls without DM (age 63.3 ± 9.1 years; 111 females). Subjects with diabetes-related renal or ophthalmological complications or insulin treatment at baseline (n = 50) were defined as severe DM. 3T MR images of the right knee were assessed for articular cartilage T2 , including texture and laminar analyses derived from the patella, medial, and lateral femur and tibia and for structural abnormalities using the modified whole-organ magnetic resonance imaging score (WORMS). Clustered linear regression analyses were used to assess associations of DM with MRI findings.ResultsDM subjects had significantly higher cartilage T2 in the patella (mean difference 0.92 msec [95% confidence interval (CI) 0.79, 1.06]; P = 0.001) and medial femur (mean difference 0.36 msec [95% CI 0.27, 0.81]; P = 0.006) compared to controls. Averaged over all compartments, DM subjects showed significantly higher texture parameters (variance, P = 0.001; contrast, P = 0.002; entropy, P < 0.001). Subjects with severe DM additionally showed higher T2 in the medial tibial deep and superficial layers (P = 0.011 and P = 0.041) compared to controls. No significant differences in cartilage, meniscus, and overall WORMS were found between the groups (P > 0.05).ConclusionIn comparison to nondiabetic controls, cartilage in DM subjects showed higher and more heterogeneous cartilage T2 values, indicating increased articular cartilage degeneration. This affected even more compartments in subjects with severe DM.Level of evidence2 Technical Efficacy: 5 J. Magn. Reson. Imaging 2018;47:380-390.

ObjectiveTo investigate the association of cartilage degeneration with previous knee injuries not undergoing surgery, determined by morphologic and quantitative 3-T magnetic resonance imaging (MRI).Materials and methodsWe performed a nested cross-sectional study of right knee MRIs from participants in the Osteoarthritis Initiative (OAI) aged 45-79 with baseline Kellgren-Lawrence score of 0-2. Cases were 142 right knees of patients with self-reported history of injury limiting the ability to walk for at least 2 days. Controls were 426 right knees without history of injury, frequency-matched to cases on age, BMI, gender, KL scores and race (1:3 ratio). Cases and controls were compared using covariate-adjusted linear regression analysis, with the outcomes of region-specific T2 mean, laminar analysis and heterogeneity measured by texture analysis to investigate early cartilage matrix abnormalities and the Whole-Organ Magnetic Resonance Imaging Score (WORMS) to investigate morphologic knee lesions.ResultsCompared to control subjects, we found significantly higher mean T2 values in the injury [lateral tibia (28.10 ms vs. 29.11 ms, p = 0.001), medial tibia (29.70 ms vs. 30.40 ms, p = 0.014) and global knee cartilage (32.73 ms vs. 33.29 ms, p = 0.005)]. Injury subjects also had more heterogeneous cartilage as measured by GLCM texture contrast, variance and entropy (p  0.05).ConclusionA history of knee injury not treated surgically is associated with higher and more heterogeneous T2 values, but not with morphologic knee abnormalities. Our findings suggest that significant, conservatively treated knee injuries are associated with permanent cartilage matrix abnormalities.

ObjectiveThe purpose of this study was to determine the probability of structural worsening of knee cartilage and whole joint degeneration over 4-8 years based on cartilage T2 Z-scores at baseline.DesignRight knees with Kellgren-Lawrence (KL) grades of 0-2 in 587 participants from the Osteoarthritis Initiative were studied. 3T MR images were used to perform baseline cartilage T2 quantification and assess 4-year changes in cartilage morphology (WORMS scoring) in 5 regions. Changes in joint space narrowing (JSN) and KL were assessed over 8 years. T2 Z-scores were based on a reference database of knees without morphologic cartilage degeneration at baseline. Odds ratios for, and predicted probabilities of any worsening in WORMS cartilage, JSN and KL grade were obtained from logistic regression models.ResultsA one-unit increase in the baseline medial femur T2 Z-score was associated with cartilage worsening in the same region (OR = 1.59; P

Purpose To investigate the association of weight loss with progression of cartilage changes at magnetic resonance (MR) imaging over 48 months in overweight and obese participants compared with participants of stable weight. Materials and Methods The institutional review boards of the four participating centers approved this HIPAA-compliant study. Included were (a) 640 participants (mean age, 62.9 years ± 9.1 [standard deviation]; 398 women) who were overweight or obese (body mass index cutpoints of 25 and 30 kg/m2, respectively) from the Osteoarthritis Initiative, with risk factors for osteoarthritis or mild to moderate radiographic findings of osteoarthritis, categorized into groups with (a) weight loss of more than 10% (n = 82), (b) weight loss of 5%-10% (n = 238), or (c) stable weight (n = 320) over 48 months. Participants were frequency-matched for age, sex, baseline body mass index, and Kellgren-Lawrence score. Two radiologists assessed cartilage and meniscus defects on right knee 3-T MR images at baseline and 48 months by using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Progression of the subscores was compared between the weight loss groups by using multivariable logistic regression models. Results Over 48 months, adjusted mean increase of cartilage WORMS was significantly smaller in the 5%-10% weight loss group (1.6; 95% confidence interval [CI]: 1.3, 1.9; P = .002) and even smaller in the group with more than 10% weight loss (1.0; 95% CI: 0.6, 1.4; P = .001) when compared with the stable weight group (2.3; 95% CI: 2.0, 2.7). Moreover, percentage of weight change was significantly associated with increase in cartilage WORMS (β = 0.2; 95% CI: 0.02, 0.4; P = .007). Conclusion Participants who lost weight over 48 months showed significantly lower cartilage degeneration, as assessed with MR imaging; rates of progression were lower with greater weight loss. © RSNA, 2017.

ObjectivesTo evaluate the ability of different MRI sequences to detect chondrocalcinosis within knee cartilage and menisci, and to analyze the association with joint degeneration.MethodsSubjects with radiographic knee chondrocalcinosis (n = 90, age 67.7 ± 7.3 years, 50 women) were selected from the Osteoarthritis Initiative and matched to controls without radiographic chondrocalcinosis (n = 90). Visualization of calcium-containing crystals (CaC) was compared between 3D T1-weighted gradient-echo (T1GE), 3D dual echo steady-state (DESS), 2D intermediate-weighted (IW), and proton density (PD)-weighted fast spin-echo (FSE) sequences obtained with 3T MRI and correlated with a semiquantitative CaC score obtained from radiographs. Structural abnormalities were assessed using Whole-Organ MRI Score (WORMS) and logistic regression models were used to compare cartilage compartments with and without CaC.ResultsCorrelations between CaC counts of MRI sequences and degree of radiographic calcifications were highest for GE (rT1GE = 0.73, P  0.05). Meniscus WORMS was significantly higher in subjects with chondrocalcinosis compared to controls (P = 0.005). Cartilage defects were significantly more frequent in compartments with CaC than without (patella: P = 0.006; lateral tibia: P

BackgroundTo evaluate the longitudinal changes of bone marrow edema-like lesions (BMELs) in patients after anterior cruciate ligament (ACL) reconstruction and to investigate the effect of BMELs on cartilage matrix composition changes measured using MR T1ρ and T2 mapping.MethodsPatients with acute ACL tear were enrolled in a prospective study. MR imaging was performed at baseline (before surgeries) and at 6-month, 1-year and 2-year after ACL reconstruction. MR imaging included sagittal high-resolution, 3D fast spin-echo (CUBE) sequences for BMEL evaluation, and 3D T1ρ mapping and T2 mapping for cartilage assessment. BMELs were assessed using whole-organ magnetic resonance imaging score (WORMS), and the volume of BMELs was measured by a semi-automatic method. Generalized estimating equation (GEE) was used to explore association between BMELs at baseline and cartilage changes during follow-up.ResultsFifty four patients were included in the present study and 39 patients had completed 2-year follow-up. BMELs were noted in 42 injured knees (77.8%) with 105 lesions and in 7 contralateral knees (13.0%) with 9 lesions (χ2=45.763, P

Purpose To determine the incidence with which morphologic articular cartilage defects develop over 48 months in cartilage with signal abnormalities at baseline magnetic resonance (MR) imaging in comparison with the incidence in articular cartilage without signal abnormalities at baseline. Materials and Methods The institutional review boards of all participating centers approved this HIPAA-compliant study. Right knees of 90 subjects from the Osteoarthritis Initiative (mean age, 55 years ± 8 [standard deviation]; 51% women) with cartilage signal abnormalities but without morphologic cartilage defects at 3.0-T MR imaging and without radiographic osteoarthritis (Kellgren-Lawrence score, 0-1) were frequency matched for age, sex, Kellgren-Lawrence score, and body mass index with right knees in 90 subjects without any signal abnormalities or morphologic defects in the articular cartilage (mean age, 54 years ± 5; 51% women). Individual signal abnormalities (n = 126) on intermediate-weighted fast spin-echo MR images were categorized into four subgrades: subgrade A, hypointense; subgrade B, inhomogeneous; subgrade C, hyperintense; and subgrade D, hyperintense with swelling. The development of morphologic articular cartilage defects (Whole-Organ MR Imaging Score ≥2) at 48 months was analyzed on a compartment level and was compared between groups by using generalized estimating equation logistic regression models. Results Cartilage signal abnormalities were more frequent in the patellofemoral joint than in the tibiofemoral joint (59.5% vs 39.5%). Subgrade A was seen more frequently than were subgrades C and D (36% vs 22%). Incidence of morphologic cartilage defects at 48 months was 57% in cartilage with baseline signal abnormalities, while only 4% of compartments without baseline signal abnormalities developed morphologic defects at 48 months (all compartments combined and each compartment separately, P < .01). The development of morphologic defects was not significantly more likely in any of the subgrades (P = .98) and was significantly associated with progression of bone marrow abnormalities (P = .002). Conclusion Knee cartilage signal abnormalities detected with MR imaging are precursors of morphologic defects with osteoarthritis and may serve as imaging biomarkers with which to assess risk for cartilage degeneration. (©) RSNA, 2016.

PurposeThe purpose of this nested case-control study was to identify baseline, incident, and progressive MRI findings visible on standard MRI clinical sequences that were associated with development of incident knee pain in subjects at risk for OA over a period of 48 months.MethodsWe analyzed 60 case knees developing incident pain (WOMAC(pain) = 0 at baseline and WOMAC(pain) ≥ 5 at 48 months) and 60 control knees (WOMAC(pain) = 0 at baseline and WOMAC(pain) = 0 at 48 months) from the Osteoarthritis Initiative. 3 T knee MRIs were analyzed using a modified WORMS score (cartilage, meniscus, bone marrow) at baseline and after 48 months. Baseline and longitudinal findings were grouped into logistic regression models and compared using likelihood-ratio tests. For each model that was significant, a stepwise elimination was used to isolate significant MRI findings.ResultsOne baseline MRI finding and three findings that changed from baseline to 48 months were associated with the development of pain: at baseline, the severity of a cartilage lesion in the medial tibia was associated with incident pain--(odds ratio (OR) for incident pain = 3.05; P = 0.030). Longitudinally, an incident effusion (OR = 9.78; P = 0.005), a progressive cartilage lesion of the patella (OR = 4.59; P = 0.009), and an incident medial meniscus tear (OR = 4.91; P = 0.028) were associated with the development of pain.ConclusionsOur results demonstrate that baseline abnormalities of the medial tibia cartilage as well as an incident joint effusion, progressive patella cartilage defects, and an incident medial meniscus tear over 48 months may be associated with incident knee pain. Clinically, this study helps identify MRI findings that are associated with the development of knee pain.

As the most frequent cause of physical disability, musculoskeletal diseases such as arthritis and osteoporosis have a great social and economical impact. Quantitative magnetic resonance imaging (MRI) biomarkers are important tools that allow clinicians to better characterize, monitor, and even predict musculoskeletal disease progression. Post-processing pipelines often include image segmentation. Manually identifying the border of the region of interest (ROI) is a difficult and time-consuming task. Manual segmentation is also affected by inter- and intrauser variability, thus limiting standardization. Fully automatic or semi-automatic methods that minimize the user interaction are highly desirable. Unfortunately, an ultimate, highly reliable and extensively evaluated solution for joint and musculoskeletal tissue segmentation has not yet been proposed, and many clinical studies still adopt fully manual procedures. Moreover, the clinical translation of several promising quantitative MRI techniques is highly affected by the lack of an established, fast, and accurate segmentation method. The goal of this review is to present some of the techniques proposed in recent literature that have been adopted in clinical studies for joint and musculoskeletal tissue analyses in arthritis patients. The most widely used MRI sequences and image processing algorithms employed to accomplish segmentation challenges will be discussed in this paper.

This study assessed the effects of static loading on MRI relaxation times of menisci in individuals with and without radiographic knee OA. High-resolution fast spin-echo (FSE) and T(1ρ)/T(2) relaxation time MR sequences were obtained with and without loading at 50% body weight in 124 subjects. T(1ρ)/T(2) relaxation times were calculated in menisci, and meniscus lesions were assessed through clinical grading. Student's t-test compared OA and control unloaded relaxation times as well as within-group changes with loading, Generalized Linear Models evaluated zonal variation, and ANCOVA compared loading response between groups. Unloaded T(1ρ) and T(2) in the middle and inner zones of the lateral anterior horn and outer zone of the medial posterior horn were significantly higher in OA and suggest that meniscal OA change occurs unevenly. Zonal T(1ρ) and T(2) showed differing patterns between anterior and posterior horns, suggesting differences in macromolecular organization. Significant increases with loading were seen largely in the T(2) of controls and less frequently in subjects with OA. In the medial posterior horn, T(1ρ) and T(2) decreased with loading in OA but changed negligibly in controls; these significantly different loading responses between groups may indicate load transmission failure in OA menisci.

ObjectiveTo determine the characteristics of femoral condyle insufficiency fracture (FCIF) lesions and their relative associations with the risk of clinical progression.Materials and methodsThis HIPAA-compliant retrospective study was approved by our Institutional Review Board. Seventy-three patients (age range, 19-95) were included after excluding patients with post-traumatic fractures, bone marrow infarct, osteochondritis dissecans, or underlying tumor. Two board-certified musculoskeletal radiologists classified morphologic findings including lesion diameter, associated bone marrow edema pattern, and associated cartilage/meniscus damage. Electronic medical charts were evaluated for symptoms, risk factors, and longitudinal outcomes, including total knee arthroplasty (TKA). Imaging characteristics were correlated with clinical findings, and comparison of outcome groups was performed using a regression model adjusted for age.ResultsThe majority of patients with FCIF were women (64.4%, 47/73), on average 10 years older than men (66.28 ± 15.86 years vs. 56.54 ± 10.39 years, p = 0.005). The most common location for FCIF was the central weight-bearing surface of the medial femoral condyle; overlying full thickness cartilage loss (75.7%, 53/70) and ipsilateral meniscal injury (94.1%, 64/68) were frequently associated. Clinical outcomes were variable, with 23.9% (11/46) requiring TKA. Cartilage WORMS score, adjacent cartilage loss, and contralateral meniscal injury, in addition to decreased knee range of motion at presentation, were significantly associated with progression to TKA (p

PurposeTo evaluate a pulse sequence combining stimulated echo diffusion preparation with a 3D segmented spoiled gradient echo (SPGR) acquisition for diffusion tensor imaging (DTI) of knee cartilage in healthy and osteoarthritis (OA) populations for early diagnosis and characterization of OA.MethodsDiffusion-weighted images of 40 subjects (20 healthy, 20 OA) at baseline and 20 subjects (10 healthy, 10 OA) at one year were obtained. The subjects were classified according to Kellgren Lawrence (KL) and whole organ magnetic resonance imaging scoring (WORMS) method acquired at 3 T. Cartilage full thickness and laminar mean diffusivity (MD) and fractional anisotropy (FA) values were quantified. The reproducibility of MD and FA values was assessed in five healthy human subjects based on test-retest scans.ResultsIn general, the full thickness MD values were higher in subjects with knee OA compared to healthy controls in both the baseline and follow up cohort. Laminar analysis MD and FA results were significantly different (p

Study designControlled laboratory study, longitudinal design.ObjectiveTo examine whether baseline knee flexion moment or impulse during walking is associated with the progression of osteoarthritis (OA) with magnetic resonance imaging of the patellofemoral joint (PFJ) at 1 year.BackgroundPatellofemoral joint OA is highly prevalent and a major source of pain and dysfunction. The biomechanical factors associated with the progression of PFJ OA remain unclear.MethodsThree-dimensional gait analyses were performed at baseline. Magnetic resonance imaging of the knee (high-resolution, 3-D, fast spin-echo sequence) was used to identify PFJ cartilage and bone marrow edema-like lesions at baseline and a 1-year follow-up. The severity of PFJ OA progression was defined using the modified Whole-Organ Magnetic Resonance Imaging Score when new or increased cartilage or bone marrow edema-like lesions were observed at 1 year. Peak external knee flexion moment and flexion moment impulse during the first and second halves of the stance phase of gait were compared between progressors and nonprogressors, and used to predict progression after adjusting for age, sex, body mass index, and presence of baseline PFJ OA.ResultsSixty-one participants with no knee OA or isolated PFJ OA were included. Patellofemoral joint OA progressors (n = 10) demonstrated significantly higher peak knee flexion moment (P = .01) and flexion moment impulse (P = .04) during the second half of stance at baseline compared to nonprogressors. Logistic regression showed that higher peak knee flexion moment during the second half of the stance phase was significantly associated with progression at 1 year (adjusted odds ratio = 3.3, P = .01).ConclusionPeak knee flexion moment and flexion moment impulse during the second half of stance are related to the progression of PFJ OA and may need to be considered when treating individuals who are at risk of or who have PFJ OA.

BackgroundWomen are at a greater risk for knee osteoarthritis (OA), but reasons for this greater risk in women are not well understood. It may be possible that differences in cartilage composition and walking mechanics are related to greater OA risk in women.Questions/purposes(1) Do women have higher knee cartilage and meniscus T1ρ than men in young healthy, middle-aged non-OA and OA populations? (2) Do women exhibit greater static and dynamic (during walking) knee loading than men in young healthy, middle-aged non-OA and OA populations?MethodsData were collected from three cohorts: (1) young active (1) (18 men, 25 women). T1ρ and T2 relaxation times for cartilage in the medial knee, lateral knee, and patellofemoral compartments and medial and lateral menisci were quantified with 3.0-T MRI. A subset of the participants underwent three-dimensional motion capture during walking for calculation of peak knee flexion and adduction moments, flexion and adduction impulses, and peak adduction angle. Differences in MR, radiograph, and gait parameters between men and women were compared in the three groups separately using multivariate analysis of variance.ResultsWomen had higher lateral articular cartilage T1ρ (men=40.5 [95% confidence interval {CI}, 38.8-42.3] ms; women=43.3 [95% CI, 41.9-44.7] ms; p=0.017) and patellofemoral T1ρ (men=44.4 [95% CI, 42.6-46.3] ms; women=48.4 [95% CI, 46.9-50.0] ms; p=0.002) in the OA group; and higher lateral meniscus T1ρ in the young group (men=15.3 [95% CI, 14.7-16.0] ms; women=16.4 [95% CI, 15.6-17.2] ms; p=0.045). The peak adduction moment in the second half of stance was lower in women in the middle-aged (men=2.05 [95% CI, 1.76-2.34] %BW*Ht; women=1.66 [95% CI, 1.44-1.89] %BW*Ht; p=0.037) and OA (men=2.34 [95% CI, 1.76-2.91] %BW*Ht; women=1.42 [95% CI, 0.89-1.94] %BW*Ht; p=0.022) groups. Static varus from radiographs was lower in women in the middle-aged (men=178° [95% CI, 177°-179°]; women=180° [95% CI, 179°-181°]; p=0.002) and OA (men=176° [95% CI, 175°-178°]; women=180° [95% CI, 179°-181°]; p