T2 map signal variation predicts symptomatic osteoarthritis progression: data from the Osteoarthritis Initiative.
ABSTRACT: The aim of this work is to use quantitative magnetic resonance imaging (MRI) to identify patients at risk for symptomatic osteoarthritis (OA) progression. We hypothesized that classification of signal variation on T2 maps might predict symptomatic OA progression.Patients were selected from the Osteoarthritis Initiative (OAI), a prospective cohort. Two groups were identified: a symptomatic OA progression group and a control group. At baseline, both groups were asymptomatic (Western Ontario and McMaster Universities Arthritis [WOMAC] pain score total <10) with no radiographic evidence of OA (Kellgren-Lawrence [KL] score???1). The OA progression group (n?=?103) had a change in total WOMAC score greater than 10 by the 3-year follow-up. The control group (n?=?79) remained asymptomatic, with a change in total WOMAC score less than 10 at the 3-year follow-up. A classifier was designed to predict OA progression in an independent population based on T2 map cartilage signal variation. The classifier was designed using a nearest neighbor classification based on a Gaussian Mixture Model log-likelihood fit of T2 map cartilage voxel intensities.The use of T2 map signal variation to predict symptomatic OA progression in asymptomatic individuals achieved a specificity of 89.3 %, a sensitivity of 77.2 %, and an overall accuracy rate of 84.2 %.T2 map signal variation can predict symptomatic knee OA progression in asymptomatic individuals, serving as a possible early OA imaging biomarker.
Project description:OBJECTIVE:There is an interest in using Magnetic Resonance Imaging (MRI) to identify pre-radiographic changes in osteoarthritis (OA) and features that indicate risk for disease progression. The purpose of this study is to identify image features derived from MRI T2 maps that can accurately predict onset of OA symptoms in subjects at risk for incident knee OA. METHODS:Patients were selected from the Osteoarthritis Initiative (OAI) control cohort and incidence cohort and stratified based on the change in total Western Ontario and McMaster Universities Arthritis (WOMAC) score from baseline to 3-year follow-up (80 non-OA progression and 88 symptomatic OA progression patients). For each patient, a series of image texture features were measured from the baseline cartilage T2 map. A linear discriminant function and feature reduction method was then trained to quantify a texture metric, the T2 texture index of cartilage (TIC), based on 22 image features, to identify a composite marker of T2 heterogeneity. RESULTS:Statistically significant differences were seen in the baseline T2 TIC between the non-progression and symptomatic OA progression populations. The baseline T2 TIC differentiates subjects that develop worsening of their WOMAC score OA with an accuracy between 71% and 76%. The T2 TIC differences were predominantly localized to a dominant knee compartment that correlated with the mechanical axis of the knee. CONCLUSION:Baseline heterogeneity in cartilage T2 as measured with the T2 TIC index is able to differentiate and predict individuals that will develop worsening of their WOMAC score at 3-year follow-up.
Project description:OBJECTIVE:The objective of this study was to assess the clinical significance of increased fluorine-18-fluorodeoxyglucose (F-FDG) uptake on PET/CT in joints for evaluation of symptomatic osteoarthritis (OA) and prediction of progression. PATIENTS AND METHODS:In this prospective study, shoulder, hip, and knee joints were imaged in 65 patients undergoing routine F-FDG PET/CT imaging. Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire to assess joint pain, stiffness, and physical function. Standardized uptake values (SUVs) were measured in hip, knee, acromioclavicular (AC), and glenohumeral (GH) joints. Scout PET/CT images were evaluated for OA using the Kellgren and Lawrence (K/L) system. Patients were followed-up for 5 years to determine the progression of OA on the basis of follow-up imaging or surgical intervention. RESULTS:SUV of knee (r=0.309, P=0.0003), hip (r=0.260, P=0.0027), AC (r=0.186, P=0.0313), and GH (r=0.191, P=0.0271) joints correlated with WOMAC overall scores. Furthermore, SUV of knee (r=0.410, P<0.0001), hip (r=0.203, P=0.0199), and AC (r=0.364, P<0.0001) joints correlated with K/L scores. The area under the receiver operating characteristic curves for SUV were 0.734 (knee), 0.678 (hip), 0.661 (AC), and 0.544 (GH) for symptomatic OA detection based on WOMAC overall z-score greater or equal to 2. Compared with K/L score [hazard ratio (HR)=0.798, P=0.5324], age (HR=0.992, P=0.8978), and WOMAC overall score (HR=1.089, P=0.1265), only SUV (HR=5.653, P=0.0229) was an independent predictor of OA progression in the knees. CONCLUSION:F-FDG PET/CT may be helpful with localization of painful abnormalities in the inflamed regions of the joints, which could potentially be used to direct individualized treatment in moderate and severe OA. Furthermore, SUV measurement on F-FDG PET/CT could serve as an inflammation activity index in the knees that may be predictive of outcomes and progression rate of OA.
Project description:BACKGROUND:Osteoarthritis (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. PURPOSE:To 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 TYPE:Retrospective. SUBJECTS:641 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/SEQUENCE:MR images were obtained using 3.0T. ASSESSMENT:Compartment-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 TESTS:Best subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA. RESULTS:Model 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 CONCLUSION:We 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 EVIDENCE:2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526.
Project description:Little is known about the temporal evolution of pain severity in persons with knee osteoarthritis (OA). We sought to describe the pain trajectory over 6 years in a cohort of subjects with radiographic, symptomatic knee OA.We used data from the Osteoarthritis Initiative (OAI), a multi-center, longitudinal study of subjects with diagnosed radiographic evidence of knee OA. Pain was assessed at baseline and annually for 6 years. Our analysis cohort included subjects with symptomatic knee OA at baseline, defined as baseline Kellgren-Lawrence (KL) score ?2 with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score >0. We used group-based trajectory modeling to identify distinct patterns of pain progression over a 6-year follow-up. Factors examined included sex, race, education, comorbidities, age, body mass index (BMI), alignment, KL grade, and depression.We used data from 1753 OAI participants with symptomatic knee OA. Mean baseline WOMAC pain score was 26.5 (0-100, 100=worst) with standard deviation (SD) 19. Group-based trajectory modeling identified five distinct pain trajectories; baseline pain scores for each ranged from 15 to 62. None of the trajectories exhibited substantial worsening. One fifth of subjects in the two trajectories with the greatest pain underwent total knee replacement (TKR) over follow-up. Higher KL grade, obesity, depression, medical comorbidities, female sex, non-white race, lower education, and younger age were associated with trajectories characterized by greater pain.We found that knee pain changes little, on average, over 6 years in most subjects. These observations suggest knee OA is characterized by persistent rather than inexorably worsening symptoms.
Project description:OBJECTIVE:To examine cross-sectional and longitudinal between-group differences of infra-patellar fat pad (IPFP) size and magnetic resonance imaging (MRI) signal from fat-suppressed intermediate-weighted images with clinically relevant symptomatic and radiographic progression of knee osteoarthritis (OA), vs healthy references. METHODS:We studied 110 case knees (Kellgren-Lawrence Grade [KLG1-3]) with radiographic (?0.7 mm loss in joint space width [JSW]) and symptomatic progression (?+9/100 units on the Western Ontario and McMasters Universities Osteoarthritis Index [WOMAC] knee pain subscale) vs 118 control knees without progression from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium cohort. We further studied 88 knees from the Osteoarthritis Initiative (OAI) healthy reference cohort without (risk factors) of knee OA. The IPFP was manually segmented using baseline and year-2 sagittal fat-suppressed intermediate-weighted spin-echo 3 T MRIs. Baseline measures and longitudinal change in IPFP volume and 3D MRI signal (mean, standard deviation [SD]) were compared between groups. RESULTS:No statistically significant baseline differences in IPFP volume, 3D MRI signal mean or signal heterogeneity (SD) were observed between progressor and non-progressor OA knees. Yet, the IPFP 3D MRI signal SD, but not its volume, was statistically significantly greater in OA vs healthy knees. No statistically significant 2-year changes in IPFP volume were observed in either group, but the increase in 3D MRI signal heterogeneity (SD) was greater in progressor vs non-progressor knees, and was greater in OA vs healthy knees. CONCLUSION:Whereas IPFP-related morphometric measures did not statistically significantly differ between groups, a stronger increase in 3D IPFP MRI signal and signal heterogeneity may be associated with radiographic/symptomatic progression of OA, when compared to non-progressive OA or healthy knees.
Project description:Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls. This study included 389 participants [229 fallers (≥2 falls or one injurious fall in the past 12 months), 160 non-fallers (no history of falls)], age (≥65 years) from a randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT). Physical function was assessed using Timed Up and Go (TUG) and Functional Reach (FR) tests. Knee and hip OA were diagnosed using three methods: Clinical, Radiological and Self-report. OA symptom severity was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The total WOMAC score was categorized to asymptomatic, mild, moderate and severe symptoms. Individuals with radiological OA and 'mild' overall symptoms on the WOMAC score had reduced risk of falls compared to asymptomatic OA [OR: 0.402(0.172-0.940), p = 0.042]. Individuals with clinical OA and 'severe' overall symptoms had increased risk of falls compared to those with 'mild' OA [OR: 4.487(1.883-10.693), p = 0.005]. In individuals with radiological OA, mild symptoms appear protective of falls while those with clinical OA and severe symptoms have increased falls risk compared to those with mild symptoms. Both relationships between OA and falls were not mediated by physical limitations. Larger prospective studies are needed for further evaluation.
Project description:<h4>Background</h4>Despite the overall success of total hip replacement (THR) in patients with symptomatic osteoarthritis (OA), up to one-quarter of patients report suboptimal recovery. The aim of this study was to determine whether social support and general self-efficacy predict variability in short-term recovery in a Norwegian cohort.<h4>Methods</h4>We performed secondary analysis of a prospective multicenter study of 223 patients who underwent THR for OA in 2003-2004. The total score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3 months after surgery was used as the recovery variable. We measured self-efficacy using the General Self-Efficacy Scale (GSES) and social support with the Social Provisions Scale (SPS). Preoperative and postoperative scores were compared using Wilcoxon tests. The Mann-Whitney U test compared scores between groups that differed in gender and age. Spearman's rho correlation coefficients were used to evaluate associations between selected predictor variables and the recovery variable. We performed univariate and multiple linear regression analyses to identify independent variables and their ability to predict short-term recovery after THR.<h4>Results</h4>The median preoperative WOMAC score was 58.3 before and 23.9 after surgery. The mean absolute change was 31.9 (standard deviation [SD] 17.0) and the mean relative change was 54.8% (SD 26.6). Older age, female gender, higher educational level, number of comorbidities, baseline WOMAC score, self-efficacy, and three of six individual provisions correlated significantly with short-term recovery after THR and predicted the variability in recovery in the univariate regression model. In multiple regression models, baseline WOMAC was the most consistent predictor of short-term recovery: a higher preoperative WOMAC score predicted worse short-term recovery (??=?0.44 [0.29, 0.59]). Higher self-efficacy predicted better recovery (??=?-0.44 [-0.87, -0.02]). Reliable alliance was a significant predictor of improved recovery (??=?-1.40 [-2.81, 0.01]).<h4>Conclusions</h4>OA patients' general self-efficacy and the expectation of others' tangible assistance predict recovery after THR. Researchers and clinicians should target these psychosocial factors together with the patients and their families to improve the quality of care and surgical outcomes.
Project description:<h4>Purpose</h4>To assess reliability and clinical utility of evaluating stress-related metaphyseal water distribution using a semi-quantitative Dixon MRI-based method for early diagnosis of physeal stress injuries in adolescent gymnasts.<h4>Methods</h4>Twenty-four gymnasts with clinically suspected overuse injury of the distal radial physis, 18 asymptomatic gymnasts, and 24 non-gymnast controls aged 12?±?1.5 years prospectively underwent hand radiographs and 3T MRI of the wrist including coronal T1-weighted and T2-weighted Dixon sequences. Two raters measured metaphyseal water signal fraction in 13 radial and ulnar regions of interest (ROI). Inter- and intrarater reliability, interslice (between 3 middle radial slices), and inter-ROI (between 3 ROIs on same level) reliability were assessed using intraclass correlation coefficients (ICC). Water signal fractions and their within-person ratios in distal versus most proximal ROIs were compared between groups using one-way analysis of variance.<h4>Results</h4>Inter- and intrarater ICCs were 0.79-0.99 and 0.94-1.0 for T1-weighted, and 0.88-1.0 and 0.88-1.0 for T2-weighted Dixon. Interslice and inter-ROI ICCs were 0.55-0.94 and 0.95-0.97 for T1-weighted, and 0.70-0.96 and 0.96-0.97 for T2-weighted Dixon. Metaphyseal water signal fraction in symptomatic gymnasts was higher in six distal ROIs compared with asymptomatic gymnasts and in nine ROIs compared with non-gymnasts (p?<?0.05). Metaphyseal water score (ratio of distal versus most proximal ROIs) was 1.61 in symptomatic gymnasts and 1.35 in asymptomatic gymnasts on T2-weighted Dixon (p?<?0.05).<h4>Conclusion</h4>Semi-quantitative Dixon MRI-based water signal fraction assessment has good to excellent reproducibility and shows increased metaphyseal water scores in symptomatic gymnasts compared with asymptomatic gymnastic peers.<h4>Key points</h4>• The proposed Dixon MRI-based semi-quantitative method for assessment of metaphyseal bone marrow water content is reliable, with off-the-shelf availability and short scan times. • The metaphyseal water score allows comparisons between gymnasts using a within-person reference area for unaffected metaphyseal bone. • As metaphyseal water score was increased in symptomatic gymnasts compared with asymptomatic gymnasts, this semi-quantitative method can potentially be used as an indicator of bone marrow edema in the early diagnosis of gymnastic physeal stress injury.
Project description:To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life.This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables.A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident.Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA.
Project description:<h4>Background</h4>Knee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP.<h4>Methods</h4>Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall).<h4>Results</h4>The BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively).<h4>Conclusions</h4>Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections. Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.