Fixed-flexion Knee Radiographs Research Articles

Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study

Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range:-0.18,-0.24) exceeded that for 2D JSWx (-0.10,-0.16). Responsiveness of 3D JSW subregional mean (-0.06,-0.36) and maximal (-1.14,-1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P≤0.002). Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Trajectories of Structural Disease Progression in Knee Osteoarthritis.

Knee osteoarthritis (OA) is a heterogeneous disease, with most patients experiencing slow disease progression and some with rapid deterioration. We aimed to identify groups of patients with symptomatic knee OA experiencing rapid structural progression. We selected participants from the Osteoarthritis Initiative with baseline Kellgren/Lawrence (K/L) grades 1-3 and knee pain, and with joint space width (JSW) on fixed-flexion knee radiographs assessed at baseline and with ≥1 follow-up over 8 years. We used latent class growth analysis to identify subgroups of JSW progression, jointly modeling time to knee replacement (KR) to account for potential informative dropouts. After identifying trajectories, we used logistic regression to assess the association between baseline characteristics and the JSW trajectory group. We used data from 1,578 participants. Baseline radiographic severity was K/L grade 1 in 17%, K/L grade 2 in 50%, and K/L grade 3 in 33%. We identified 3 distinct JSW trajectories: 86% stable, 6% with stable JSW followed by late progression, and 8% with early progression. Incorporating information about KR resulted in 47% of KRs initially classified as stable being reclassified to 1 of the progressing trajectories. Prior knee surgery was associated with being in the late-progressing versus the stable trajectory, while obesity was associated with being in the early-progressing versus stable trajectory. In addition to a subgroup of individuals experiencing early structural progression, 8-year longitudinal data allowed the identification of a late-progressing trajectory. Incorporating information about KR was important to properly identify longitudinal structural trajectories in knee OA.

The Prevalence of Knee Symptoms, Radiographic, and Symptomatic Osteoarthritis at Four Time Points: The Johnston County Osteoarthritis Project, 1999-2018.

ObjectiveTo describe point prevalence of knee symptoms, radiographic knee osteoarthritis (rKOA), severe rKOA, and symptomatic rKOA at four time points in the longitudinal, population‐based Johnston County Osteoarthritis Project (JoCo OA).MethodsData were from 2573 JoCo OA participants with up to 18 years of follow‐up (1999‐2018) and standardized fixed‐flexion knee radiographs read by a single, reliable expert musculoskeletal radiologist. The four outcomes were 1) self‐reported knee symptoms, defined by “On most days, do you have pain, aching, or stiffness in your right/left knee?”; 2) rKOA, defined as a Kellgren‐Lawrence grade (KLG) of 2 to 4); 3) severe rKOA, defined as a KLG of 3 or 4; and 4) symptomatic rKOA, defined as both symptoms and rKOA in the same joint. Weighted prevalence estimates and 95% confidence intervals (CIs) were generated overall and by age group, sex, race, and body mass index (BMI).ResultsMost recently (2017‐2018, T4), the overall prevalence (percentage) of knee symptoms, rKOA, severe rKOA, and symptomatic rKOA was 41% (95% CI: 35‐47%), 61% (95% CI: 56‐67%), 35% (95% CI: 30‐40%), and 30% (95% CI: 24‐35%), respectively. From time point T1 to T4, prevalence increased for rKOA, severe rKOA, and symptomatic rKOA but not for knee symptoms. The prevalence of both severe rKOA (17‐39%) and symptomatic rKOA (23‐30%) was consistently higher among women. The prevalence of all outcomes was higher among those with higher BMI and among Black participants at all time points, particularly rKOA (35‐69%) and severe rKOA (22‐46%).ConclusionThese updated estimates demonstrate a large and increasing burden of knee OA, particularly among women and Black individuals.

The combination of an inflammatory peripheral blood gene expression and imaging biomarkers enhance prediction of radiographic progression in knee osteoarthritis

ObjectivePredictive biomarkers of progression in knee osteoarthritis are sought to enable clinical trials of structure-modifying drugs. A peripheral blood leukocyte (PBL) inflammatory gene signature, MRI-based bone marrow lesions (BML) and meniscus extrusion scores, meniscal lesions, and osteophytes on X-ray each have been shown separately to predict radiographic joint space narrowing (JSN) in subjects with symptomatic knee osteoarthritis (SKOA). In these studies, we determined whether the combination of the PBL inflammatory gene expression and these imaging findings at baseline enhanced the prognostic value of either alone.MethodsPBL inflammatory gene expression (increased mRNA for IL-1β, TNFα, and COX-2), routine radiographs, and 3T knee MRI were assessed in two independent populations with SKOA: an NYU cohort and the Osteoarthritis Initiative (OAI). At baseline and 24 months, subjects underwent standardized fixed-flexion knee radiographs and knee MRI. Medial JSN (mJSN) was determined as the change in medial JSW. Progressors were defined by an mJSN cut-point (≥ 0.5 mm/24 months). Models were evaluated by odds ratios (OR) and area under the receiver operating characteristic curve (AUC).ResultsWe validated our prior finding in these two independent (NYU and OAI) cohorts, individually and combined, that an inflammatory PBL inflammatory gene expression predicted radiographic progression of SKOA after adjustment for age, sex, and BMI. Similarly, the presence of baseline BML and meniscal lesions by MRI or semiquantitative osteophyte score on X-ray each predicted radiographic medial JSN at 24 months. The combination of the PBL inflammatory gene expression and medial BML increased the AUC from 0.66 (p = 0.004) to 0.75 (p < 0.0001) and the odds ratio from 6.31 to 19.10 (p < 0.0001) in the combined cohort of 473 subjects. The addition of osteophyte score to BML and PBL inflammatory gene expression further increased the predictive value of any single biomarker. A causal analysis demonstrated that the PBL inflammatory gene expression and BML independently influenced mJSN.ConclusionThe use of the PBL inflammatory gene expression together with imaging biomarkers as combinatorial predictive biomarkers, markedly enhances the identification of radiographic progressors. The identification of the SKOA population at risk for progression will help in the future design of disease-modifying OA drug trials and personalized medicine strategies.

Applying Densely Connected Convolutional Neural Networks for Staging Osteoarthritis Severity from Plain Radiographs.

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 ± 9.2years, BMI = 32.8 ± 15.9kg/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.

THU0224 Knee Effusion is A Risk Factor for Prevalence and Progression of Bone Marrow Lesions: A Population-Based Study

BackgroundBone marrow lesions (BML) occur commonly in knee osteoarthritis (OA) and may be a target for intervention in randomized controlled trials. The potential benefit of therapeutic interventions in OA is...

Reliability of a uni-compartmental scale for the radiographic evaluation of knee arthritis: data from the multicenter osteoarthritis study

Reliability of a uni-compartmental scale for the radiographic evaluation of knee arthritis: data from the multicenter osteoarthritis study

Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months

As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. Subjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

Intra- and inter-observer reproducibility of volume measurement of knee cartilage segmented from the OAI MR image set using a novel semi-automated segmentation method

We developed a semi-automated method based on a graph-cuts algorithm for segmentation and volumetric measurements of the cartilage from high-resolution knee magnetic resonance (MR) images from the Osteoarthritis Initiative (OAI) database and assessed the intra- and inter-observer reproducibility of measurements obtained via this method. MR image sets from 20 subjects of varying Kellgren-Lawrence (KL) grades (from 0 to IV) on fixed flexion knee radiographs were selected from the baseline double-echo and steady-state (DESS) knee MR images in the OAI database (0.B.1 Imaging Data set). Two trained radiologists independently performed the segmentation of knee cartilage twice using the semi-automated method. The volumes of segmented cartilage were computed and compared. The intra- and inter-observer reproducibility were determined by means of the coefficient of variation (CV%) of repeated cartilage segmented volume measurements. The subjects were also divided into the low- (0, I or II) and high-KL (III or IV) groups. The differences in cartilage volume measurements and CV% within and between the observers were tested with t tests. The mean (+/-SD) intra-observer CV% for the 20 cases was 1.29 (+/-1.05)% for observer 1 and 1.67 (+/-1.14)% for observer 2, while the mean (+/-SD) inter-observer CV% was 1.31 (+/-1.26)% for session 1 and 1.79 (+/-1.72)% for session 2. There was no significant difference between the two intra-observer CV%'s (P=0.272) and between the two inter-observer CV%'s (P=0.353). The mean intra-observer CV% of the low-KL group was significantly smaller than that for the high-KL group for observer 1 (0.83 vs 1.86%: P=0.025). The segmentation processing times used by the two observers were significantly different (observer 1 vs 2): (mean 49+/-12 vs 33+/-6min) for session 1 and (49+/-8 vs 32+/-8min) for session 2. The semi-automated graph-cuts method allowed us to segment and measure cartilage from high-resolution 3T MR images of the knee with high intra- and inter-observer reproducibility in subjects with varying severity of OA.

Quantitative analysis of subchondral sclerosis of the tibia by bone texture parameters in knee radiographs: site-specific relationships with joint space width

To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.

Reproducibility of computer-assisted joint alignment measurement in OA knee radiographs

(1) To investigate the reproducibility of computer-assisted measurements of knee alignment angle (KA) from digitized radiographs of osteoarthritis (OA) participants requiring total knee arthroplasty (TKA) and (2) to determine whether landmark choice affects the precision of KA measurements on radiographs. Using a custom algorithm, femoral, central, and tibial measurement-guiding rules were interactively placed on digitized posteroanterior fixed-flexion knee radiographs by mouse control and positioned according to different anatomic landmarks. The angle subtended by lines connecting these guiding rules was measured by three readers to assess interobserver, intraobserver and experience-inexperience reproducibility. Test-retest reproducibility was evaluated with duplicate radiographs from a healthy cohort. Reproducibility was assessed using root-mean square coefficients of variation (RMSCV%). The Bland-Altman method was performed on data obtained from varying anatomic landmarks (confidence interval, CI= 95%). From 16 healthy and 30 TKA participants, reproducibility analyses revealed a high degree of intraobserver (n=38, RMSCV=0.56%), interobserver (n=38, RMSCV=0.72%), test-retest (n=16, RMSCV=0.87%) and experience-inexperience (n=38, RMSCV=0.73%) reproducibility with variances below 1%. Varying the orientation of tibial and femoral rules according to anatomic landmarks produced a difference that exceeded an a priori limit of agreement of -1.11 degrees to +1.67 degrees. Our custom-designed software provides a robust method for measuring KAs within digitized knee radiographs. Although test-retest analyses were only performed in a healthy cohort, we anticipate a similar degree of reproducibility in an OA sample. A standardized set of anatomic landmarks employed for KA measurement is recommended since arbitrary selection of landmarks resulted in imprecise KA measurement even with a computer-assisted technique.

Fixed-flexion knee radiography: the sensitivity to detect knee joint space narrowing in osteoarthritis

Independent reports on the longitudinal performance of non-fluoroscopic fixed-flexion knee radiography have not been published. Therefore, we evaluated the sensitivity of fixed-flexion radiography to detect knee joint space narrowing (JSN) over 2 years in patients with osteoarthritis (OA) and compared the effect of reproducibility and quality of medial tibial plateau (MTP) alignment on sensitivity to JSN. Fixed-flexion radiographs of both knees of 193 OA patients were obtained at baseline and after 24 months. Minimum joint space width (JSW) of the medial tibiofemoral joint spaces was measured manually in paired digitised radiographs without knowledge of the chronology. The degree of MTP alignment was assessed by measuring the distance between the anterior and posterior margins of the MTP (intermargin distance [IMD]). Accurate repositioning was achieved if, in the 24-month radiograph, the IMD was reproduced to within 1mm. The quality of MTP alignment was satisfactory if the IMD was <or=1mm. The mean (standard deviation [SD]) JSN between baseline and 24 months was 0.18 (0.49)mm and the standardised response mean (SRM) was 0.37. The SRM was 0.36 in the knee film pairs (86%) in which the IMD was accurately reproduced after 24 months and 0.52 in the film pairs (42%) with satisfactory MTP alignment on both the baseline and 24-month radiographs. The sensitivity to radiographic JSN on fixed-flexion knee radiographs over 2 years was higher in satisfactorily aligned than accurately reproduced serial pairs of radiographs. These findings have implications for longitudinal knee OA studies using fixed-flexion radiographs.