Bone Marrow Lesion Volume Research Articles

Automatic Segmentation of Bone Marrow Lesions on MRI Using a Deep Learning Method.

Bone marrow lesion (BML) volume is a potential biomarker of knee osteoarthritis (KOA) as it is associated with cartilage degeneration and pain. However, segmenting and quantifying the BML volume is challenging due to the small size, low contrast, and various positions where the BML may occur. It is also time-consuming to delineate BMLs manually. In this paper, we proposed a fully automatic segmentation method for BMLs without requiring human intervention. The model takes intermediate weighted fat-suppressed (IWFS) magnetic resonance (MR) images as input, and the output BML masks are evaluated using both regular 2D Dice similarity coefficient (DSC) of the slice-level area metric and 3D DSC of the subject-level volume metric. On a dataset with 300 subjects, each subject has a sequence of 36 IWFS MR images approximately. We randomly separated the dataset into training, validation, and testing sets with a 70%/15%/15% split at the subject level. Since not every subject or image has a BML, we excluded the images without a BML in each subset. The ground truth of the BML was labeled by trained medical staff using a semi-automatic tool. Compared with the ground truth, the proposed segmentation method achieved a Pearson's correlation coefficient of 0.98 between the manually measured volumes and automatically segmented volumes, a 2D DSC of 0.68, and a 3D DSC of 0.60 on the testing set. Although the DSC result is not high, the high correlation of 0.98 indicates that the automatically measured BML volume is strongly correlated with the manually measured BML volume, which shows the potential to use the proposed method as an automatic measurement tool for the BML biomarker to facilitate the assessment of knee OA progression.

Larger Pre-operative Tibial Bone Marrow Lesion Volume Correlates with Better Clinical Outcomes after Medial Opening High Tibial Osteotomy

Larger Pre-operative Tibial Bone Marrow Lesion Volume Correlates with Better Clinical Outcomes after Medial Opening High Tibial Osteotomy

Short-Term Effects of Genicular Artery Embolization on Symptoms and Bone Marrow Abnormalities in Patients with Refractory Knee Osteoarthritis

PurposeTo evaluate the short-term outcomes of genicular artery embolization (GAE) for knee osteoarthritis (OA) with and without bone marrow lesion (BML) and/or subchondral insufficiency fracture of the knee (SIFK). Materials and MethodsThis single-institution prospective observational pilot study analyzed 24 knees in 22 patients with mild to moderate knee OA, including 8 knees without BML, 13 knees with BML, and 3 knees with both BML and SIFK. The area and volume of BMLs on magnetic resonance images were measured before and after GAE. Baseline and postoperative pain and physical function were assessed using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). ResultsGAE significantly reduced the BML area and volume 3 months after embolization in the knees with BML (both P < .0005). GAE significantly decreased the VAS scores at 3 and 6 months after embolization in patients without BML (both P = .04) and those with BML (both P = .01). GAE also lowered the WOMAC scores 3 months after embolization in patients without and with BML (P = .02 and P = .0002, respectively). However, GAE did not significantly alter the BML area and volume (both P = .25), VAS scores (P = 1.00), and WOMAC scores (P = .08) in patients with BML and SIFK at 3 months after GAE. ConclusionsThis observational pilot study suggested that GAE effectively reduces the BML area and volume and improves pain and physical function in patients with knee OA accompanied by BML but is inefficacious in those with both BML and SIFK.

Correlation Between Vitamin D and Degenerative Joint Disorders: Review and Meta-Analysis

Objective: Evaluate the evidence of the clinical correlation between vitamin D and symptomatic degenerative joint disease. Methods: A systematic search and meta-analysis was conducted of randomized controlled studies (RCTs) published in between January 1st, 2010, and March 30th, 2020 on five different databases. The study population consisted of adult patients with symptomatic knee osteoarthritis; the intervention was vitamin D; the comparison was placebo, and the outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC) (pain, function, stiffness), tibial cartilage volume, synovial tissue volume (STV), subchondral bone marrow lesion (BML) volume, effusion-synovitis, serum vitamin D3 levels, serological inflammatory and metabolic biomarkers levels and adverse events. Results: Nine RCTs involving 2,168 patients were included in this study. Pooled estimates suggested that vitamin D supplementation was associated with reduction in WOMAC pain (Std. Mean=1.08(0.90, 1.25); I2=99%; p=0.00001), function (Mean=1.1(0.92, 1.27); I2=99%; p=0.00001), stiffness (Std. mean= 0.72(0.54, 0.90); I2=98%; p=0.00001) and synovial effusion in the suprapatellar pouch numbers. There was no significant difference in tibial cartilage volume incidence (Std. Mean=0.26(0.44, 0.80); I2=99%; p=0.00001), STV, BML volume, inflammatory biomarkers and adverse events between the vitamin D and the placebo groups. Conclusion: Vitamin D supplementation was effective in improving WOMAC pain and function in patients with knee OA and also improved serological vitamin D levels. However, it had no beneficial effect on structural cartilage change or inflammatory biomarker reduction. Therefore, there is currently a lack of evidence on vitamin D regimen dosage and length to obtain benefits in preventing knee disease progression.

Larger bone marrow lesion volume before medial open-wedge high tibial osteotomy correlates with better improvement of clinical scores in patients with knee osteoarthritis.

This study evaluated the clinical outcomes of medial open-wedge high tibial osteotomy (MOWHTO) and bone marrow lesion (BML) scores and volumes. The hypotheses were that quantitative BML volume is more associated with clinical outcomes of MOWHTO than qualitative BML evaluations, and pre-operative BML volume is associated with the improvement of clinical outcomes. Patients who underwent MOWHTO were retrospectively enrolled. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was recorded before the initial surgery and at plate removal surgery. Using pre-operative short-time inversion recovery magnetic resonance imaging, BMLs were evaluated using three qualitative scores, reflecting the maximum length, proportion, and intensity of BML. For quantification, BMLs of the femur and tibia were separately defined as lesions with a threshold greater than the mean signal intensity plus two standard deviations, using the corresponding lateral condyles as controls. The association between the KOOS scales and BML scores/volume was evaluated using Spearman's correlation coefficient. Multivariate linear regression analyses for post-operative KOOS scales were performed using the tibial BML volume as one of the four independent variables. The final analysis included 40 MOWHTO cases. Two qualitative BML scores correlated only with pre-operative KOOS sports. Femoral and tibial BML volumes were correlated with post-operative KOOS QOL (ρ = 0.40, p = 0.01) and sports (ρ = 0.36, p = 0.02), respectively. Tibial BML volume was significantly correlated with all five delta KOOS scales (ρ = 0.39-0.51, p = 0.01-0.001), however, femoral BML volume was only correlated with delta KOOS QOL (ρ = 0.41, p = 0.01). In multivariate analyses, tibial BML volume was a significant positive predictor for every post-operative KOOS scale, while post-operative % mechanical axis was also a positive significant variable, except post-operative KOOS pain. Tibial BML volume was positively correlated with one post-operative KOOS scale and all delta KOOS scales. A larger pre-operative tibial BML and appropriate alignment correction were associated with a better post-operative KOOS scales. Pre-operative large BML had no negative influence on post-operative clinical outcomes; hence, surgeons need not hesitate to perform MOWHTO in patients with large BMLs in the medial condyles. Retrospective case series, Level IV.

Novel Framework for Measuring Whole Knee Osteoarthritis Progression Using Magnetic Resonance Imaging.

We developed and validated a set of composite scores that combine quantitative magnetic resonance imaging (MRI)-based measurements of hyaline cartilage damage, bone marrow lesions (BMLs), and effusion-synovitis into composite scores. We selected 300 participants (n=100 for development cohort; n=200 for validation cohort) from the Osteoarthritis Initiative with complete clinical, radiographic, and MRI data at baseline and 24 months. We used semiautomated programs to quantify tibiofemoral and patellar cartilage damage, BML volume, and whole-knee effusion-synovitis volume. The candidate composite scores were formed by summing changes from baseline to 24 months based on prespecified methods. We evaluated the candidate composite scores for 1) the ability to differentiate groups with and without knee osteoarthritis progression (17 radiographic and patient-reported definitions), 2) sensitivity to change (standardized response means), and 3) relative performance relating to legacy outcome measures of knee osteoarthritis progression. Three of 13 developed composite scores qualified for testing in the validation cohort (ranked by sensitivity to change): whole-knee cumulative cartilage damage, unweighted total knee score, and BML plus effusion-synovitis volume. Change in cumulative cartilage damage associated with radiographic progression (Kellgren/Lawrence grade: odds ratio [OR] 1.84; joint space width progression: OR 2.11). Changes in the unweighted total knee score (OR 1.97) and BML plus effusion-synovitis score (OR 1.92) associated with Western Ontario and McMaster Universities Osteoarthritis Index knee pain progression. Two composite scores emerged, reflecting discrete domains of knee osteoarthritis progression. First, cumulative damage, which is measured by a whole-knee cartilage damage score, reflects the damage accrued over time. Second, dynamic disease activity, which is measured by a BML plus effusion-synovitis score, relates to changes in a patient's state of disease and symptoms.

Animal Models of Bone Marrow Lesions in Osteoarthritis.

ABSTRACTBone marrow lesions are abnormalities in magnetic resonance images that have been associated with joint pain and osteoarthritis in clinical studies. Increases in the volume of bone marrow lesions have been associated with progression of joint degeneration, leading to the suggestion that bone marrow lesions may be an early indicator of—or even a contributor to—cartilage loss preceding irreversible damage to the joint. Despite evidence that bone marrow lesions play a role in osteoarthritis pathology, very little is known about the natural history of bone marrow lesions and their contribution to joint degeneration. As a result, there are limited data regarding the cell activity within a bone marrow lesion and any associated bone‐cartilage cross‐talk. Animal models provide the best approach for understanding bone marrow lesions at their early, reversible stages. Here, we review the few animal studies of bone marrow lesions. An ideal animal model of a bone marrow lesion occurs in joints large enough to accurately measure bone marrow lesion volume. Additionally, the ideal animal model would facilitate the study of bone‐cartilage cross‐talk by generating the bone marrow lesion immediately adjacent to subchondral bone and would do so without causing direct damage to neighboring soft tissues to isolate the effects of the bone marrow lesion on cartilage loss. Early reports demonstrate the feasibility of such an animal model. Given the irreversible nature of osteoarthritic changes in the joint, factors such as bone marrow lesions that are present early in disease pathogenesis remain an enticing target for new therapeutic approaches. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Statin use and MRI subchondral bone marrow lesion worsening in generalized osteoarthritis: longitudinal analysis from Osteoarthritis Initiative data.

To determine the association between statin therapy and knee MRI-detected subchondral bone marrow lesion (BML) longitudinal worsening in patients with Heberden's nodes (HNs) as the hallmark of generalized osteoarthritis (OA) phenotype. All participants gave informed consent, and IRB approved HIPAA-compliant protocol. We assessed the worsening in BML volume and number of affected subregions in the Osteoarthritis Initiative (OAI) participants with HNs at baseline clinical examination (HN+), using the semi-quantitative MRI Osteoarthritis Knee Scores at baseline and 24months. Participants were classified according to baseline BML involvement as "no/minimal" (≤ 2/14 knee subregions affected and maximum BML score ≤ 1) or "moderate/severe." Statin users and non-users were selected using 1:1 propensity-score (PS) matching for OA and cardiovascular disease (CVD)-related potential confounding variables. We assessed the association between statin use and increasing BML score and affected subregions using adjusted mixed-effect regression models. The PS-matched HN+ participants (63% female, aged 63.5 ± 8.5-year-old) with no/minimal and moderate/severe BML cohorts consisted of 332 (166:166, statin users: non-users) and 380 (190:190) knees, respectively. In the HN+ participants with no/minimal BML, statin use was associated with lower odds of both BML score worsening (odds ratio, 95% confidence interval: 0.62, 0.39-0.98) and increased number of affected subregions (0.54, 0.33-0.88). There was no such association in HN- participants or those HN+ participants with baseline moderate/severe BML. In patients with CVD indications for statin therapy and generalized OA phenotype (HN+), statin use may be protective against the OA-related subchondral bone damage only in the subgroup of participants with no/minimal baseline BML. • Statin use may reduce the risk of subchondral bone damage in specific osteoarthritis patients with a generalized phenotype, minimal subchondral bone damage, and cardiovascular statin indications.

Fast quantitative bone marrow lesion measurement on knee MRI for the assessment of osteoarthritis

ObjectiveKnee osteoarthritis (KOA) is a prevalent disease with a high economic and social cost. Magnetic resonance imaging (MRI) can be used to visualize many KOA-related structures including bone marrow lesions (BMLs), which are associated with OA pain. Several semi-automated software methods have been developed to segment BMLs, using manual, labor-intensive methods, which can be costly for large clinical trials and other studies of KOA. The goal of our study was to develop and validate a more efficient method to quantify BML volume on knee MRI scans. Materials and methodsWe have applied a deep learning approach using a patch-based convolutional neural network (CNN) which was trained using 673 MRI data sets and the segmented BML masks obtained from a trained reader. Given the location of a BML provided by the reader, the network performed a fully automated segmentation of the BML, removing the need for tedious manual delineation. Accuracy was quantified using the Pearson's correlation coefficient, by a comparison to a second expert reader, and using the Dice Similarity Score (DSC). ResultsThe Pearson's R2 value was 0.94 and we found similar agreement when comparing two readers (R2 ​= ​0.85) and each reader versus the DL model (R2 ​= ​0.95 and R2 ​= ​0.81). The average DSC was 0.70. ConclusionsWe developed and validated a deep learning-based method to segment BMLs on knee MRI data sets. This has the potential to be a valuable tool for future large studies of KOA.

COMPARISON BETWEEN BML VOLUMES FROM A SEMI-AUTOMATED SOFTWARE METHOD AND BML VOLUMES FROM A DEEP LEARNING ALGORITHM: DATA FROM THE OSTEOARTHRITIS INITIATIVE (OAI)

MRI can be used to assess several structural changes related to knee OA (KOA) including bone marrow lesions (BMLs), which are important structural biomarkers linked to pain and disease progression. Software image analysis methods have been shown to provide objective quantitative measurements of BML volume, and deep learning (DL) algorithms offer the potential to eliminate or reduce the reader time substantially. The goal of our study was to compare BML volumes determined by a deep learning (DL) algorithm to those measured by a well-validated semi-automated (SA) approach and, ultimately, demonstrate that the DL algorithm can be used in place of the SA method. We measured BML volumes in index knees of 700 subjects from the OAI at the BL, 12mo and 24mo time points, for a total of 2,084 knees, using the SA and DL methods. The DL method used a U-Net convolutional neural network (CNN) with 5 convolution levels and was trained using Dice coefficients. Each knee was subdivided into several sub regions: femur (F), tibia (T), patella (P), medial femur, tibia, and patella (MF, MT, MP) lateral femur, tibia, and patella (LF, LT, and LP), the trochlea (TR) and a measure of the patellofemoral (PF) subregion defined as the combination of P and TR. A least-squared fit was performed comparing the DL and SA for the total knee BML volume and each of the sub regions. Figure 1 shows scatter and Bland Altmam plots of the DL versus SA total knee volume, demonstrating a strong correlation but an apparent bias as the DL method consistently underestimates the SA volume for larger values. The table provides the slopes and R 2 values for total knee and sub regions. While there was a strong association between the DL and SA methods, a consistent bias was evident across all sub regions in the deviation of the slopes from a value of 1. The reason for the bias appears to be the diffuse nature of BMLs on MRI and the fact that the DL algorithm does not capture all such voxels. Whether an alternative to training with Dice, or the application of a correction factor can be applied merits further investigation. The results suggest that the DL approach may be useful for future studies that require processing of a large number of MRI scans. NIH AR071409 DICLOSURE STATEMENT ACKNOWLEDGMENT CORRESPONDENCE ADDRESS: jduryea@bwh.harvard.edu

Associations of osteoclastogenesis and nerve growth in subchondral bone marrow lesions with clinical symptoms in knee osteoarthritis.

Background/objectiveSubchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms.MethodsTotal 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n ​= ​14; BMLs without cyst group, n ​= ​37; BMLs with cyst group, n ​= ​19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms.ResultsIn BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p ​< ​0.05). Subchondral osteoclastogenesis and nerve distribution were positively associated with joint pain in BMLs with cyst group (p ​< ​0.05).ConclusionThe subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain.The translational potential of this articleOur results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.

Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma

This study conducted the possibilities of diffusion-weighted magnetic resonance imaging of the whole body diffusion WB-MRI (in comparison with positron emission tomography with computed tomography PET/CT) in assessing the volume and prevalence of the tumor, as well as determining bone marrow (BM) damage (for various cytological types) in the diagnosis and staging of the disease in patients with FL. A prospective comparative search study included 15 patients (4 men and 11 women, with a median age of 53 years) with newly diagnosed FL. Patients have not received antitumor chemotherapy previously. After the diagnosis was established, all patients (with the blindness of both the cases themselves and some specialists regarding the results of other specialists) were examined by PET/CT and diffusion WB-MRI, after which a BM examination was performed (histological examination and determination of B-cell clonality in BM puncture by PCR). Using the diffusion WB-MRI method, the prevalence of tumor lesion (nodal and extranodal foci) in each patient was estimated, and the total tumor volume was calculated, BM lesion was detected, and BM lesion volume was calculated. For lesions of different localization, the measured diffusion coefficient (DC) of the diffusion WB-MRI and the standardized rate of accumulation of the radiopharmaceutical in tissues (SUV) of the PET/CT method were determined and compared with each other (for the same areas). Statistical analysis was performed using the estimate of agreement (by Cohens kappa coefficient and asymptotic test) of the results of the compared methods. Estimates of the prevalence of tumor damage (lymph nodes and extranodal foci) using the diffusion WB-MRI and PET/CT methods were the same. High DC and SUV were observed in the peripheral lymph nodes, extranodal foci and bulky, low DC and SUV in the foci of BM. All 4 methods successfully determined BM damage, however, the diffusion WB-MRI had comparatively less negative results. The highest values of SUV and CD were noted in cases of the 3 grade of FL. Using the diffusion WB-MRI method, the prevalence of tumor lesion was assessed in each patient (nodal and extranodal foci were detected) and the total tumor volume was calculated, BM lesion detection was performed, and the volume of BM lesion was calculated. It is important to note that with the help of diffusion WB-MRI, it was possible to measure separately the total tumor volume (462025 cm3) and separately the volume of bulky (251358 cm3). The diffusion WB-MRI allowed us to differentiate the volume of tumor tissue (reduced as a result of treatment) and residual (fibrous-adipose) tissue in residual formations (which averaged 21% of the initial volume). The predictors of a poor antitumor response were the maximum SUV values (more than 14.0) and the minimum DC values (0.510-3mm2/s) in the BM foci. The diffusion WB-MRI allows for detailed visualization of BM lesions and surrounding soft tissues both in the debut of the FL and in the process of tracking the effectiveness of chemotherapy, which makes it possible to use it along with PET/CT. Diffusion WB-MRI allows to separately evaluate the volume of true tumor tissue and residual tissue. Cases of the 3 grade of FL (including the transformation of FL into diffuse B-large cell lymphoma) are isolated due to low DC values (and high SUV values) in the tumor tissue. BM foci of FL lesion also have (in comparison with nodal and extranodal foci) lower DC values. The predictors of a poor antitumor response were high (from 14.0 or more) SUV valuesin the tumor (and especially in bulky), and low (about 0.5103mm2/s) DC values of BM foci. The PET/CT and diffusion WB-MRI have proven to be reliable diagnostic tools for establishing the stage of FL and detecting BM damage. Diffusion WB-MRI for FL is an informative first-line diagnostic method that allows regular monitoring of the disease and early detection of foci of relapse and disease progression.

The relation of oral bisphosphonates to bone marrow lesion volume among women with osteoarthritis

Bone marrow lesions (BMLs) contribute to pain and progression of knee OA. Bisphosphonates may be a potential disease-modifier through amelioration of BMLs. We sought to determine the effect of oral bisphosphonates on BML volume over 12 months. Women in the Osteoarthritis Initiative who newly initiated an oral bisphosphonate were propensity-score matched to non-initiators. BML volume was assessed using sagittal turbo spin echo fat-suppressed intermediate-weighted MR images at the index date and 12 months later. A validated semi-automated process was used to segment subchondral OA-related BMLs to determine total volume of BMLs based on number of voxels within the outlined area of interest. Mean change in BML volume over 12 months among bisphosphonate initiators was compared with non-initiators using multiple linear regression. 145 bisphosphonate initiators were identified, who were well-matched to their comparators. The difference in mean change in total BML volume between the two groups, regardless of presence of baseline BMLs, was not significant (P=0.4, 95% CI -156.6 to+354.2). The proportion of participants with decreased, increased, or unchanged BML volumes over the 12 months were similar in both groups. Among those with baseline BMLs, bisphosphonate initiators had a greater proportion with a decrease in BML volume compared with stable or increased BML volume than non-initiators (P=0.03). In this 'real-world' setting of women starting bisphosphonates, we found no clear evidence of benefit on BML volume over a 12-month period, though a trend towards a decrease in BML volume was noted.

Composite quantitative knee structure metrics predict the development of accelerated knee osteoarthritis: data from the osteoarthritis initiative

BackgroundWe aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis.MethodsWe used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL). We assessed tibiofemoral cartilage damage (four regions: medial/lateral tibia/femur), bone marrow lesion (BML) volume (four regions: medial/lateral tibia/femur), and whole knee effusion-synovitis volume on 3 T MR images with semi-automated programs. We calculated two MR-based composite scores. Cumulative damage was the sum of standardized cartilage damage. Disease activity was the sum of standardized volumes of effusion-synovitis and BMLs. We focused on annual images from 2 years before to 2 years after radiographic onset (or a matched time for those without knee osteoarthritis). To determine between group differences in the composite metrics at all time points, we used generalized linear mixed models with group (3 levels) and time (up to 5 levels). For our prognostic analysis, we used multinomial logistic regression models to determine if one-year worsening in each composite metric change associated with future accelerated knee osteoarthritis (odds ratios [OR] based on units of 1 standard deviation of change).ResultsPrior to disease onset, the accelerated KOA group had greater average disease activity compared to the typical and no KOA groups and this persisted up to 2 years after disease onset. During a pre-radiographic disease period, the odds of developing accelerated KOA were greater in people with worsening disease activity [versus typical KOA OR (95% confidence interval [CI]): 1.58 (1.08 to 2.33); versus no KOA: 2.39 (1.55 to 3.71)] or cumulative damage [versus typical KOA: 1.69 (1.14 to 2.51); versus no KOA: 2.11 (1.41 to 3.16)].ConclusionsMR-based disease activity and cumulative damage metrics may be prognostic markers to help identify people at risk for accelerated onset and progression of knee osteoarthritis.

Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteenyear follow-up.

Recently, mesenchymal stem cells (MSCs) have been proposed as potential treatment modalities for knee osteoarthritis. However, indications and long-term results have not been frequently reported. The purpose of this study was to determine whether bone marrow lesion on MRI are predictive of risk progression to total knee arthroplasty during the first ten years after subchondral cell therapy. This study included 140 adults aged 65 to 90years. These 140 patients (mean age 75.4 ± 14.2years) planned to undergo staged-bilateral total knee arthroplasty (TKA) for medial osteoarthritis, had "comparable" pain in both knees, and accepted randomization of the knees for surgery. They received TKA on one side and a subchondral injection of MSCs (from iliac bone marrow concentrate) on the contralateral knee during the same anaesthetic. The bone marrow graft of 20cm3 volume (10cc in the tibia and 10cc in the femur) contained average 7800 MSCs/mL (range 3120 to 11,560). The baseline volume of bone marrow lesions (BMLs) on the tibia and on the femoral condyle determined on MRI was average 3.4cm3 (range 0.4 to 6.4cm3). The risk of subsequent knee arthroplasty due to absence of bone marrow lesions regression as well as osteoarthritis (OA) grade was evaluated with Cox proportional-hazards ratio after control of baseline variables (number of cells injected, age, knee alignment). After treatment with MSCs injection in bone marrow lesions of the subchondral bone, medial femorotibial compartment BML volume experienced regression over 24months (mean regression 1.5cm3, range 0.8 to 3.2cm3). At the most recent follow up (average of 15years, range 10 to 20years), a total of 25 (18%) of the 140 patients underwent total knee arthroplasty performed at a mean of ten years (range, 5 to 15years) after the date of the cell therapy. The overall incidence of knee arthroplasty after cell therapy was 1.19% per person-year which was equivalent to the risk of a revision for a primary TKA in the contralateral knees of the same patient population (21 revisions, corresponding to 1.00% revision per person-year; p = 0.34). After adjusting for confounders, persistent BMLs larger than 3cm3 after cell therapy was a strong independent risk factor for total knee arthroplasty (hazard ratio HR = 4.42 [95% CI = 2.34 to 7.21]; p < 0.001), regardless of OA grade, with higher risks demonstrated for larger BMLs. Incidence rates of arthroplasty were also higher for young patients and for knees presenting severe malalignment. This study showed that subchondral bone marrow concentrate (as compared with TKA) had a sufficient effect on pain to postpone or avoid the TKA in the contra lateral joint of patients with bilateral osteoarthritis. Bone marrow lesions were predictive factors for future knee arthroplasty in the knee with subchondral cell therapy at ten years follow-up.

The effect of footwear and foot orthoses on patellofemoral bone marrow lesion volume in individuals with patellofemoral osteoarthritis

Purpose: Foot orthoses and footwear interventions are effective at improving pain in people with patellofemoral osteoarthritis (PFOA). However, the mechanism of effect is unclear. Knee braces have been shown to reduce pain and bone marrow lesion (BML) volume in individuals with PFOA. The primary aim of this study was to determine whether foot orthoses and footwear reduce BML volume in individuals with PFOA. The secondary aim was to explore the relationship between change in BML volume and change in pain.

Association between Bone marrow lesions & synovitis and symptoms in symptomatic knee osteoarthritis

Bone marrow lesions (BMLs) on MRI are typically subchondral in location, however, a proportion occur at knee ligament attachments and also include a cyst-like component. Our aim was to determine whether the volume of BML subtypes and synovial tissue volume (STV) was associated with symptoms in symptomatic knee OA. Images were acquired in a sub-sample who had taken part in a randomised trial of vitamin D therapy in knee OA (UK-VIDEO). Contrast-enhanced (CE) MRI was performed annually. In those who had ≥1 follow-up and a baseline scan (N=50), STV and BML volume was assessed. BMLs were categorised by location and by the presence/absence of a cyst-like component. WOMAC was assessed annually. We used fixed-effects panel-regression modelling to examine the association between volume and symptoms. There was no association between knee pain and total subchondral BML volume (b=0.3 WOMAC units, 95% CI -0.3 to 1.0) or total ligament-based BML volume (b=1.9, 95% CI -1.6 to 5.3). The volume of subchondral BMLs with a cyst-like component was not associated with pain (b=0.8, 95% CI -0.5 to 2.1) however, the volume of the cyst-like component itself was associated with pain (b=51.8, 95% CI 14.2 to 89.3). STV was associated with pain (b=2.2, 95% CI 0.6 to 3.7). The volume of the cyst-like component from subchondral BMLs with a cyst-like component was associated with knee pain. BML location, however, did not influence symptoms. STV was also associated with knee symptoms.

Diagnostic accuracy of dual-energy CT for detection of bone marrow lesions in the subacutely injured knee with MRI as reference method.

Dual-energy computer tomography (DECT) can detect post-traumatic bone marrow lesions. Prospective studies of the knee with large numbers of participants and intra-observer agreement assessment are limited. To investigate the diagnostic accuracy of DECT in detecting bone marrow lesions as well as estimating the bone marrow lesion volume in patients with suspected anterior cruciate ligament trauma with magnetic resonance imaging (MRI) as reference standard. Forty-eight consecutive patients with suspected anterior cruciate ligament injury were imaged bilaterally with DECT within a mean of 25 days (range 4-55 days) following injury and MRI within seven days of DECT. Two readers analyzed DECT virtual non-calcium-blinded images. Consensus MRI was reference standard. Intra- and inter-observer agreement were determined using weighted kappa statistics. Sensitivity, specificity, and negative and positive predictive values were calculated. Bone marrow lesion volumes were measured; for comparison, intra-class correlation coefficient was used. The 48 patients (26 men, 22 women; mean age 23 years, age range 15-37 years) were imaged bilaterally yielding 52 knees with bone marrow lesions, of which 44 were in the femur and 41 were in the tibia. Intra- and inter-observer agreement to detect bone marrow lesions was moderate and fair to moderate (κ 0.54-0.66, 95% confidence interval [CI] 0.39-0.80 and 0.37-0.41, 95% CI 0.20-0.57) and overall sensitivity and specificity were 70.1% and 69.1%, respectively. Positive and negative predictive values were 72.9% and 66.1%, respectively. Bone marrow lesion volumes showed excellent intra- and inter-observer agreement (0.83-0.91, 95% CI 0.74-0.94 and 0.76-0.78, 95% CI 0.57-0.87). The diagnostic performance of DECT to detect bone marrow lesions in the subacutely injured knee was moderate with intra- and inter-observer agreement ranging from moderate to substantial and fair to moderate. Bone marrow lesion volume correlation was excellent.

Effect of cane use on bone marrow lesion volume in people with medial tibiofemoral knee osteoarthritis: randomized clinical trial

To evaluate effects of daily cane use for 3 months on medial tibiofemoral bone marrow lesion (BML) volumes in people with medial tibiofemoral osteoarthritis (OA). In this randomized controlled trial (RCT), 79 participants with medial tibiofemoral OA were randomized to either a cane group (using a cane whenever walking) or control group (not using any gait aid) for 3 months. The cane group received a single training session by a physiotherapist, using a biofeedback cane to teach optimal technique and body weight support and motor learning principles to facilitate retention of learning. The primary outcome was change in total medial tibiofemoral BML volume (per unit bone volume) measured from magnetic resonance imaging (MRI) at 3 months. Secondary outcomes were BML volumes (per unit bone volume) of the medial tibia and femur, and patient-reported outcomes of overall knee pain, knee pain on walking, physical function, perceived global symptom changes and health-related quality of life. MRI analyses were performed by a blinded assessor. Seventy-eight participants (99%) completed the primary outcome. Mean (standard deviation) daily cane use was 2.3 (1.7) hours over 3 months. No evidence of between-group differences was found for change in total medial tibiofemoral BML volume (mean difference:-0.0010 (95% confidence intervals:-0.0022, 0.0003)). Most secondary outcomes showed minimal differences between groups. Daily use of a cane during walking for 3 months aiming to reduce knee joint loading did not change medial tibiofemoral BML volumes compared to no use of gait aids. Australian New Zealand Clinical Trial Registry (ACTRN12614000909628).

Application of deep learning for the quantitative assessment of bone marrow lesions (BMLs)

Purpose: MRI can be used to assess several structural changes related to knee OA (KOA). Software image analysis methods provide objective, fully quantitative measurements of these changes. However, such methods generally require a human reader and can be time consuming if the number of images in a study is large. Deep leaning (DL), a form of statistical machine learning, offers the potential for increased or full automation, therefore reducing reader time substantially. The goal of our study was to validate a DL method for segmenting (outlining) bone marrow lesions (BMLs) on knee MRI scans. Methods: We used the baseline, 12 mo. and 24 mo. scans from the 600 subjects included in the FNIH Study, a nested case/control sub study of the OAI. All 600 subjects had both BL and 24 month scans, while 582 were imaged at the 12 month time point. Therefore, the dataset included 2 or 3 scans for each of the 600 subjects, totaling 1782 scans. Selecting for subjects with a BML in at least one time point gave 1358 scans from 544 different subjects for further processing. These 544 subjects were randomly split into training, validation and test sets of 50% (673 scans, 272 subjects) / 25% (352 scans, 186 subjects), 25% (333 scans, 186 subjects), respectively. BMLs segmented using a previously-validated semi-automated (SA) method were used to train the DL algorithm. A U-Net convolutional neural network was trained on BML patches and corresponding segmentation mask pairs determined from the SA method. The U-Net model is a fully-convolutional network (FCN) architecture specifically designed for image segmentation tasks. The DL algorithm was provided with the general location of each BML. We compared the BML volumes determined with the DL software to the SA measurements. The Dice similarity coefficients (DSC) and Pearson’s R2 are reported. In Figure 1 we show a representative example of BMLs segmented with SA and DL. Results: The average DSC was 0.70 and Figure 2 is a plot comparing the SA to the DL methods. The Pearson’s R2 was 0.94. Figure 3 depicts typical segmentation results over a range of DSC values. The DL method is not fully automated since a reader is required to indicate the location of a BML. However, this step requires on average 30 seconds per scan compared to 5 minutes for the full SA method. Conclusions: We have shown that the DL approach can produce an accurate method to assess BML volume, offering substantial time savings (90%) over the SA method. Future work will investigate a fully automated method, which does not require a reader to initially locate BMLs.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)