{"title":"CAN REGISTRATION-BASED LOCATION-INDEPENDENT MEASUREMENT INCREASE THE SENSITIVITY TO BETWEEN-GROUP DIFFERENCES IN LONGITUDINAL CHANGE OF LAMINAR CARTILAGE T2?","authors":"W. Wirth , F. Eckstein","doi":"10.1016/j.ostima.2025.100331","DOIUrl":"10.1016/j.ostima.2025.100331","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Location-independent measurements of cartilage thinning and thickening were shown to be more sensitive to differences in longitudinal change between groups than location-based measures [1,2]. They remove the link between the magnitude and direction of the change and its location, and hence are sensitive to local changes in the joint, independent of where they occur. Location-independent measures of T2 lengthening and shortening computed from 16 femorotibial subregions have been previously applied to a model of early OA. The model compared 3y T2 change in KLG 0 knees with contralateral (CL) joint space narrowing (JSN) vs that in KLG 0 knees with CL KLG 0 (controls) [3]. In this model, location-independent measures were found to provide similar discrimination between these two groups as location-based measures. However, location-independent measures obtained across all individual voxels in the joint (instead of subregions) have been previously suggested to provide more detailed insights into OA-related cartilage thickness changes [4], but no study previously evaluated the sensitivity of such voxel-based shortening and lengthening scores to differences in change of laminar T2.</div></div><div><h3>OBJECTIVE</h3><div>To compare the sensitivity of voxel-based location-independent lengthening and shortening T2 scores to between-group differences in longitudinal change vs. the previously established technique of subregion-based location-independent and location-based measures in the above early OA model.</div></div><div><h3>METHODS</h3><div>Multi-echo spin-echo (MESE) MRIs were acquired at year 1 and 4 in the OAI (3T Trio, Siemens). We studied 39 KLG 0 knees with CL JSN, and 39 matched controls (criteria: same sex pain frequency, similar age (±5y) and BMI (±5kg/m<sup>2</sup>)) with bilateral KLG 0 [2]. Segmentation of the 4 femorotibial cartilages (medial/lateral tibia: MT/LT and central medial/lateral femoral condyle: cMF/cLF) was performed manually by experienced readers. Laminar T2 was computed for each segmented cartilage voxel and classified as deep or superficial, based on the distance to the cartilage surfaces. Location-based and subregion-based location-independent measures were obtained as described previously [2]. Voxel-based location-independent changes in laminar T2 were derived, summarizing the negative/positive changes across all voxels, for each of the femorotibial cartilages using the voxel-based approach (Fig. 1) These were then summarized across the entire femorotibial joint (FTJ). Location-based, subregion-based location independent, and voxel-based location-independent laminar T2 change was compared between the CL JSN vs. control knees using Cohen's D as a measure of effect size with 95% confidence intervals obtained using boot-strapping.</div></div><div><h3>RESULTS</h3><div>In the deep layer, location-based longitudinal change in femorotibial T2 revealed a Cohen’s D between both groups of 0.37 [0.04, 0.","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100331"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"THE INFLUENCE OF WEIGHT-BEARING AND FLEXION ON 3D JOINT SPACE WIDTH IN KNEE OSTEOARTHRITIS","authors":"F.F.J. Simonis , W.M. Brink , F.F. Schröder , W.C. Verra , T.D. Turmezei , S.C. Mastbergen , M.P. Jansen","doi":"10.1016/j.ostima.2025.100320","DOIUrl":"10.1016/j.ostima.2025.100320","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>In knee OA, radiographic JSW is used as a surrogate for MRI-measured cartilage thickness, though they often do not correlate well. Variations in positioning between radiography (weight-bearing semi-flexion) and MRI (non-weight-bearing extension) may contribute to discrepancies.</div></div><div><h3>OBJECTIVE</h3><div>This study aimed to evaluate differences in 3D JSW and cartilage thickness distribution between these positions in knee OA patients.</div></div><div><h3>METHODS</h3><div>21 symptomatic knee OA patients (KLG 2/3) were included. Exclusion criteria included prior knee surgery, MRI ineligibility, inability to stand unassisted for 15 minutes, or knee width > 15 cm (knee coil limit). A knee MRI protocol was performed using a 0.25T weight-bearing MRI system (G-scan Brio, Esaote). A coronal 3D dual-echo SSFP sequence (SHARC) was acquired to obtain images with an isotropic resolution of 0.66mm in both extended and flexed knee positions under weight-bearing conditions by rotating the system to 81°. Both scans were repeated under non-weight-bearing conditions by rotating the system to a horizontal position (0°). Knee flexion angles were measured, and the femur and tibia bones were segmented in 3D Slicer. 3D models were exported to Stradview to measure the tibia-femur distance at each vertex as a measure of JSW. The models and data were registered to canonical surfaces in wxRegSurf and further analyzed in MATLAB using the Surfstat package for statistical parametric mapping to derive p-values corrected for multiple vertex-wise comparisons.</div></div><div><h3>RESULTS</h3><div>The average knee angles of the 21 patients were 7.4±3.7° (extended) and 19.1±5.5° (flexed). The average JSW ranged from 3.1 mm to 14.7 mm across patients (Figure 1). A significantly smaller JSW for weight-bearing vs non-weight-bearing conditions, particularly in the outer medial and posterior lateral tibia for extended positions, and in the posterior medial tibia for flexed positions, was seen (Figure 2). Flexion increased the JSW in the anterior tibia and decreased it in the posterior tibia, particularly laterally in weight-bearing positions.</div></div><div><h3>CONCLUSION</h3><div>JSW distribution in knee OA patients varies significantly depending on both weight-bearing and knee flexion angle, and radiographic JSW measurements may not accurately reflect the joint space in non-weight-bearing positions, such as those used in MRI, especially in the lateral compartment. Currently ongoing cartilage analyses will indicate to which extent these JSW variations are attributable to changes in cartilage thickness or meniscal positioning.</div></div>","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100320"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Li , N.A. Segal , I. Tolstykh , M.C. Nevitt , T.D. Turmezei
{"title":"BASELINE C-SCORE ON WEIGHT-BEARING CT PREDICTS 2-YEAR WORSENING OF KNEE PAIN IN WOMEN","authors":"S. Li , N.A. Segal , I. Tolstykh , M.C. Nevitt , T.D. Turmezei","doi":"10.1016/j.ostima.2025.100345","DOIUrl":"10.1016/j.ostima.2025.100345","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>The B-score is a statistical score derived from non-weight-bearing MRI to assess femoral bone shape and its relationship with knee OA. However, CT scans may offer a more reliable and robust evaluations of bone shape, as they not only provide clearer differentiation between bone and soft tissue but also eliminate distortion artefact that can occur with MRI.</div></div><div><h3>OBJECTIVE</h3><div>To investigate a new “C-score” for femoral bone shape derived from CT as a predictive imaging biomarker for worsening knee pain in men and women with or at risk for knee osteoarthritis.</div></div><div><h3>METHODS</h3><div>This study included 649 knees from 389 participants (219 women) with a mean±SD age of 63.8±9.6 years and BMI of 28.5±5.0 kg/m². C-scores were calculated from baseline weight-bearing CT (WBCT) imaging of the knee joint: 0.37 mm voxels, FOV 30 × 20 cm, 120 kVp, 5.0 mA on a LineUp scanner, Curvebeam LLC, Warrington, PA. All distal femurs were segmented using Stradview to produce a surface mesh. A canonical distal femur mesh was registered using wxRegSurf to each individual femur to build the study population shape model. Each knee's C-score was derived from the distance along the vector for femur shape between the average KL0/1 and KL2/3/4 shapes from the study population using a custom script in MATLAB. A single unit of the C-score was standardized as 1SD along this vector for the KL0/1 population (Figure 1). Generalized estimating equations adjusted for age, sex, BMI and presence of up to 2 knees per participant were used to assess associations between baseline C-score and 2-year minimally clinically important worsening (MCIW) of the Western Ontario McMaster’s University Osteoarthritis Scale (WOMAC) pain subscore (2 points). MCIW is defined as the smallest difference on a pain scale that either patients perceive as worsening or requires change in treatment.</div></div><div><h3>RESULTS</h3><div>186 knees demonstrated pain worsening (32.71% women and 23.2% men). 98 knees had MCIW of pain (19.0% women and 9.8% men). C-scores ranged from -2.64 to +3.34 in women and -3.96 to +2.83 in men, with mean±SD values of 0.16±1.06 and -0.52±1.01 respectively (p-value for difference between sexes p=0.0003). Women without MCIW pain had a mean C-score of +0.31, while those with worsening pain had a mean C-score of +0.72. Men had mean C-scores of -0.03 and -0.01, respectively. In fully adjusted models, baseline C-score predicted 2-year MCIW pain (OR: 1.27, 95% CI: 1.00–1.62, p=0.047). In sex-stratified models, the odds ratios for 2-year MCIW pain in women and men were 1.49 (95% CI: 1.10–2.01, p=0.0159) and 1.01 (95% CI: 0.70–1.47, p=0.95), respectively.</div></div><div><h3>CONCLUSION</h3><div>Higher C-scores in women were significantly associated with worsening knee pain over 2 years, suggesting the C-score as a potential predictive biomarker for knee pain progression.</div></div>","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100345"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"QUANTIFYING JOINT GEOMETRY IN HUMAN HANDS FROM IMAGING DATA","authors":"C.B. Burson-Thomas","doi":"10.1016/j.ostima.2025.100281","DOIUrl":"10.1016/j.ostima.2025.100281","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>The geometry of the same joint varies substantially between people. Typical variation in merely how conforming the two subchondral bone surfaces are can increase the peak compressive stress on the articular cartilage by as much as the additional loading from becoming obese will. The mechanical environment of joint tissues is considered to play a central role in OA development. Quantifying joint geometry using repeatable, reliable, and accessible metrics supports better understanding of the relative importance (or unimportance) of this source of variability between people on their individual OA risk and this factor’s role at a population level.</div></div><div><h3>OBJECTIVE</h3><div>Previous methods of quantifying joint congruence (a measure of how conforming two surfaces are) have required detailed mathematical descriptions of the articulating surfaces and their relative position. We have developed a new method of measuring joint congruence that works directly from the 3D segmented point clouds. This has been applied to a joint in the thumb.</div></div><div><h3>METHODS</h3><div>The first step of the new methodology involves performing a Finite Element (FE) simulation of an elastic layer compressed between each set of segmented bones (Figure 1). The results of this are then interpreted using the elastic foundation model (Figure 2), enabling an equivalent, but far simpler, contact geometry to be identified. This far simpler equivalent geometry takes the form of a sphere contacting a flat surface. The identified congruence metric is the radius of this sphere, the ‘equivalent radius’, which produces an equivalent contact to that identified in each FE simulation. The minimal JSW (in this joint position) can also be estimated from the FE simulations. The new method has been applied to a small sample (n = 10) of healthy instances (5M:5F, mean age 31yrs) of the thumb metacarpophalangeal (MCP) joint (IRAS Ethics Ref: 14/LO/1059). Each participant’s right hand was CT scanned with near-isotropic voxel size (0.293 × 0.293 × 0.312 mm) and the bones segmented using a greyscale threshold.</div></div><div><h3>RESULTS</h3><div>To enable an appropriate reduction of the complex geometry represented in the 3D points clouds to one number (the radius of an equivalent ‘ball on flat’), this single parameter must continue to capture the joint’s geometry as the contact area increases. For all thumb MCP geometries tested, the force-displacement response of the elastic layer could be well-described by an identified equivalent radius, unique to that particular joint (Figure 3). The thumb MCPs had a mean equivalent radius of 17.9 mm (SD = 10.6 mm) and mean minimal JSW of 0.86 mm (SD = 0.24 mm). No relationship between congruence and joint space width was observed (Figure 4).</div></div><div><h3>CONCLUSION</h3><div>The new method can perform an efficient quantification of congruence, reducing two 3D point clouds to a single parameter. However, fu","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100281"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N.A. Segal , T. Whitmarsh , N.H. Degala , J.A. Lynch , T.D. Turmezei
{"title":"EVALUATION OF DIFFERENT METHODS OF AUTOMATED 3-D JOINT SPACE MAPPING FROM WEIGHT BEARING CT SUGGESTS A TIBIAL MESH-TO-MESH APPROACH IS MOST SENSITIVE","authors":"N.A. Segal , T. Whitmarsh , N.H. Degala , J.A. Lynch , T.D. Turmezei","doi":"10.1016/j.ostima.2025.100338","DOIUrl":"10.1016/j.ostima.2025.100338","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Weight bearing CT (WBCT) has the distinct advantage over radiography of being able to provide 3-D imaging of the knee joint while standing. It is also more practicable and better at depicting mineralized joint structures than MRI. Several different approaches to 3-D JSW measurement have been developed, but their repeatability has not been directly compared.</div></div><div><h3>OBJECTIVE</h3><div>To compare the test-retest repeatability of three different methods of 3-D joint space mapping (JSM) of the tibiofemoral compartment from WBCT imaging data.</div></div><div><h3>METHODS</h3><div>14 individuals recruited and consented at the University of Kansas Medical Center had baseline and follow-up WBCT imaging suitable for analysis. Participant demographics were: mean ± SD age 61.3 ± 8.4 years, BMI 30.7 ± 4.3 kg/m<sup>2</sup> and male:female ratio 8:6. All scanning was performed on the same XFI WBCT scanner (Planmed Oy, Helsinki, Finland) with the mean ± SD interval between baseline and follow-up attendances 14.9 ± 8.1 days. A Synaflexer<sup>TM</sup> device was used to standardize knee positioning during scanning. Imaging acquisition parameters were 96 kV tube voltage, 51.4 mA tube current, 3.5 s exposure time. A standard bone algorithm was applied for reconstruction with 0.3 mm isotropic voxels and a 21 cm vertical scan range. Both knees were included in all analyses with SD adjustments made for multiple observations from the same individual. Participant ID and scan sequence were anonymized prior to analyses. An algorithm based on U-net was implemented in C++ using LibTorch and integrated into ScanXM software for automatic segmentation of the femur and tibia from all knees. Three different JSM techniques were applied: (1) femur-to-tibia deconvolution in which the femur was the base (performed in Stradview); (2) tibia-to-femur deconvolution in which the same was done but from the tibia; and (3) tibia-to-femur mesh-to-mesh distance using a custom MATLAB script. Results from each technique were registered using wxRegSurf and displayed on their average halfway joint space mesh (i.e. the middle plane of the joint space) using custom MATLAB scripts. Bland Altman descriptive statistics were calculated as 3-D bias (follow-up minus baseline) and limit of agreement (LOA) maps for all knees. Summary statistics also included root mean square coefficient of variation (RMSCV) and LOA as a % of the mean.</div></div><div><h3>RESULTS</h3><div>3-D bias and LOA maps for all knees are displayed on the halfway joint space patches as if viewing the right knee from the inferior aspect (Figure 1). Both deconvolution techniques showed similar noise patterns of bias around a zero value, while the mesh-to-mesh technique suggested systematically wider anterior and narrower posterior JSW at follow-up, but this was of sub-millimeter magnitude. Both deconvolution techniques also showed a pattern of worsening LOA towards the joint space patch margins,","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100338"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P.G. Conaghan , A. Guermazi , N. Katz , A.R. Bihlet , D. Rom , C.M. Perkins , B. Hughes , C. Herholdt , I. Bombelka , S.L. Westbrook
{"title":"LEVI-04, A NOVEL NEUROTROPHIN-3 INHIBITOR, DEMONSTRATED SIGNIFICANT IMPROVEMENTS IN PAIN AND FUNCTION AND WAS NOT ASSOCIATED WITH DELETERIOUS EFFECTS ON JOINT STRUCTURE IN PEOPLE WITH KNEE OA IN A PHASE II RCT","authors":"P.G. Conaghan , A. Guermazi , N. Katz , A.R. Bihlet , D. Rom , C.M. Perkins , B. Hughes , C. Herholdt , I. Bombelka , S.L. Westbrook","doi":"10.1016/j.ostima.2025.100352","DOIUrl":"10.1016/j.ostima.2025.100352","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Improvement in the symptoms of osteoarthritis (OA) remains a serious unmet medical need and new pharmacological treatments are urgently needed. Excess neurotrophins (NT) are implicated in OA and other painful conditions. Previous analgesic therapies selectively targeting NGF inhibition provided improvements in pain and function, but were dose-dependently associated with significant joint pathologies, including rapidly progressive OA (RPOA). LEVI-04 is a first-in-class fusion protein (p75NTR-Fc) that supplements the endogenous p75NTR binding protein, providing analgesia via inhibition of NT-3 activity. Here we present efficacy and safety data from the phase II RCT of LEVI-04 in people with knee OA.</div></div><div><h3>METHODS</h3><div>This was a PhII multicentre (Europe and Hong Kong) RCT in people with painful (≥4/10 WOMAC), radiographic (KL≥2) knee OA. Participants were randomised to baseline then 4-weekly IV placebo or 0.3, 1, or 2mg/kg LEVI-04 through week16. The primary efficacy endpoint was assessed at week 17, safety assessments were assessed to week 20, with a telephone safety follow-up at week 30. The primary endpoint was change in WOMAC pain to week 17, with additional outcomes including function, Patient Global Assessment (PGA), 50 and 70% pain responders, a novel pain on movement assessment (the Staircase-evoked Pain Procedure, StEPP) and daily NRS pain scores. Safety and tolerability, including Adverse Events of Special Interest (AESI) concerning joint pathologies, were key secondary endpoints. X-rays of 6 large joints and MRI of knees were utilised for inclusion/exclusion criteria at baseline, and safety evaluation at week 20. All safety events involving joints were escalated to an independent Adjudication Committee.</div></div><div><h3>RESULTS</h3><div>518 people with knee OA were enrolled (mean age 63.1–65.4 years, mean BMI 29.3–30.3, female participants 51.5–61.5%). LEVI-04 demonstrated significant differences to placebo for the primary endpoint for all doses (Figure 1). WOMAC function and stiffness, PGA, daily pain scores, and StEPP were all statistically different to placebo. LEVI-04 was well tolerated, with no increased incidence of SAEs, TEAEs (Table 1) or joint pathologies, including RPOA (Table 2), compared to placebo.</div></div><div><h3>CONCLUSION</h3><div>LEVI-04 demonstrated significant and clinically meaningful improvement in pain, function and other efficacy outcomes. LEVI-04 was well tolerated at all doses studied, supporting the concept of supplementing endogenous p75NTR as a treatment for OA and other pain conditions. Phase III trials are in planning.</div></div>","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100352"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Goyal , F. Belibi , V. Sahani , R. Pedersen , Y. Vainberg , A. Williams , C. Chu , B. Haddock , G. Gold , A.S. Chaudhari , F. Kogan , A.A. Gatti
{"title":"AUTOMATING IMAGING BIOMARKER ANALYSIS FOR KNEE OSTEOARTHRITIS USING AN OPEN-SOURCE MRI-BASED DEEP LEARNING PIPELINE","authors":"A. Goyal , F. Belibi , V. Sahani , R. Pedersen , Y. Vainberg , A. Williams , C. Chu , B. Haddock , G. Gold , A.S. Chaudhari , F. Kogan , A.A. Gatti","doi":"10.1016/j.ostima.2025.100288","DOIUrl":"10.1016/j.ostima.2025.100288","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Quantitative MRI and [¹⁸F]NaF PET enable assessment of cartilage composition, bone shape, and subchondral bone metabolism in knee OA. Current workflows rely on manual segmentation that is time-consuming and subject to inter- and intra-reader variability. Furthermore, computing quantitative metrics requires considerable time and expertise. An open-source, automated, deep learning (DL) pipeline with standardized biomarker extraction has the potential to enhance reproducibility and make large-scale analysis accessible to clinical research communities, including non-technical users.</div></div><div><h3>OBJECTIVE</h3><div>Develop and validate an automated DL-based pipeline for comprehensive MRI-based segmentation and quantitative analysis of multiple knee tissues from multi-modal MR and PET images.</div></div><div><h3>METHODS</h3><div>We developed and open-sourced a comprehensive segmentation and analysis pipeline. A 2D U-Net was trained to segment 9 tissues using a dataset of 347 DESS and qDESS images: 3 bones (femur, tibia, patella), 4 cartilage regions (femoral, medial and lateral tibial, patellar), and 2 menisci (medial and lateral). Subchondral bone masks and femoral cartilage subregions were fitted automatically. Quantitative imaging biomarkers were computed as follows: cartilage T2 was computed analytically from qDESS scans; cartilage thickness was computed as the 3D Euclidean thickness of cartilage overlying the bone surface; meniscal volume was calculated as the product of voxel count and voxel volume; OA bone shape (BScore) was derived using a neural shape model; PET-derived subchondral bone metabolism was computed as regional SUVmean/max, and kinetic modeling via Hawkin’s method was used to extract KiNLR (bone mineralization rate) and K1 (perfusion to subchondral bone). To evaluate the pipeline, 20 unilateral qDESS and [¹⁸F]NaF PET knee scans (10 symptomatic OA, 10 controls) were analyzed by the automated pipeline, and two manual annotators. Manual and automated segmentations were compared using the Dice Similarity Coefficient (DSC) and average symmetric surface distance (ASSD). Biomarkers were compared using ICC and normalized mean RMSE (NRMSE).</div></div><div><h3>RESULTS</h3><div>All automated segmentations had good to excellent overlap measured using DSC (bone: 0.95-0.98; cartilage: 0.84-0.91; menisci: 0.85-0.89) and small surface errors (bone: 0.13-0.32 mm; cartilage: 0.11-0.21 mm; menisci: 0.17-0.30 mm). Notably, automated segmentations had better DSC and ASSD than the inter-rater comparison (Fig. 2). With the exception of cartilage thickness and patellar cartilage whole T2 values, all quantitative metrics showed excellent agreement with ICC >0.96 and NRMSE <0.1, comparable to inter-rater comparison. Bone metrics (BScore, SUV, PET kinetics) had ICC >0.96. Cartilage metrics had more variability, with the best reproducibility for whole cartilage T2 (ICC 0.89-0.98, NRMSE 0.01-0.04), then superficia","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F.W. Roemer , M.P. Jansen , S. Maschek , S. Mastbergen , A. Wisser , H.H. Weinans , F.J. Blanco , F. Berenbaum , M. Kloppenburg , I.K. Haugen , D.J. Hunter , A. Guermazi , W. Wirth
{"title":"DO RATES OF FEMOROTIBIAL CARTILAGE LOSS IN KELLGREN-LAWRENCE 2 AND 3 KNEES DIFFER BETWEEN THOSE WITH MILD-MODERATE VS. SEVERE PATELLOFEMORAL STRUCTURAL DAMAGE?","authors":"F.W. Roemer , M.P. Jansen , S. Maschek , S. Mastbergen , A. Wisser , H.H. Weinans , F.J. Blanco , F. Berenbaum , M. Kloppenburg , I.K. Haugen , D.J. Hunter , A. Guermazi , W. Wirth","doi":"10.1016/j.ostima.2025.100311","DOIUrl":"10.1016/j.ostima.2025.100311","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Knees with radiographic disease severity of Kellgren-Lawrence (KL) 2 and 3 are commonly included in disease-modifying (DMOAD) clinical trials of knee osteoarthritis (OA). In an eligibility context, semi-quantitative (sq) MRI assessment has been used to define structural disease severity, rule out diagnoses of exclusion, and possibly define a structural phenotype. The KL system focuses on the femorotibial joint (FTJ) only, with MRI stratification being commonly limited to the FTJ. It is unclear whether sq MRI of the patellofemoral joint (PFJ) should be included for eligibility assessment.</div></div><div><h3>OBJECTIVE</h3><div>The aim was to assess whether rates of quantitative femorotibial (FT) cartilage loss are increased for knees with semiquantitatively (sq)-defined severe patellofemoral (PF) cartilage damage and/or large bone marrow lesions (BMLs) vs. those without over a period of 24 months.</div></div><div><h3>METHODS</h3><div>626 knees with Kellgren-Lawrence 2 and 3 from the FNIH and IMI-APPROACH studies were included. MRI assessment was performed using the MRI Osteoarthritis Knee Score (MOAKS) instrument. Medial FT quantitative cartilage thickness loss was derived from baseline and 24-month manual segmentations and was compared between knees with severe vs. mild-moderate PF cartilage damage and between knees with vs. without large PF BMLs. Between-group comparisons were performed using analysis of variance (ANOVA) and were stratified by baseline medial FT cartilage damage severity (defined as mild, moderate, or severe).</div></div><div><h3>RESULTS</h3><div>410 (65%) knees were categorized as mild, 92 (15%) as moderate, and 124 (20%) as severe medial FT cartilage damage. For almost all categories of FT cartilage damage, the difference in quantitative medial FT cartilage loss was not statistically significant (<strong>Table 1</strong>). Only for the category of knees with moderate medial FT cartilage damage, statistically higher rates of quantitative medial FT cartilage loss were observed for those with large PF BMLs compared to those without (-0.245 ± 0.304 mm vs. -0.134 ± 0.218 mm) (<strong>Table 2</strong>).</div></div><div><h3>CONCLUSION</h3><div>For the large majority of sq-defined FT cartilage damage categories, no statistically significant differences in FT rates of quantitative cartilage loss were detected. Screening for PF cartilage damage and BMLs does not appear to be required in a disease-modifying OA drug trial.</div></div>","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100311"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C.T. Nielsen , M. Boesen , M. Henriksen , J.U. Nybing , S.W. Bardenfleth , C.K. Rasmussen , M.W. Brejnebøl , A.S. Poulsen , S.M. Aljuboori , K.I. Bunyoz , S. Overgaard , A. Troelsen , H. Bliddal , H. Gudbergsen , F. Müller
{"title":"AGREEMENT BETWEEN IN VIVO AND EX VIVO PHOTON-COUNTING CT MEASURES OF SUBCHONDRAL BONE FEATURES IN PATIENTS WITH KNEE OSTEOARTHRITIS","authors":"C.T. Nielsen , M. Boesen , M. Henriksen , J.U. Nybing , S.W. Bardenfleth , C.K. Rasmussen , M.W. Brejnebøl , A.S. Poulsen , S.M. Aljuboori , K.I. Bunyoz , S. Overgaard , A. Troelsen , H. Bliddal , H. Gudbergsen , F. Müller","doi":"10.1016/j.ostima.2025.100304","DOIUrl":"10.1016/j.ostima.2025.100304","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Bone changes are integral to the onset and progression of OA. Many aspects remain poorly understood due to the inability to assess bone architecture in vivo. Research has relied on ex vivo imaging, hindering evaluation of early-stage disease and longitudinal analysis. Conventional CT lacks the resolution to visualise subchondral bone microstructure. While ex vivo Photon Counting CT (PCCT) has demonstrated imaging comparable to μCT, its ability to capture bone microstructure in vivo in knee OA patients under clinical conditions remains unproven.</div></div><div><h3>OBJECTIVE</h3><div>The aim of this study was to compare in vivo and ex vivo PCCT of subchondral bone features in patients with knee OA.</div></div><div><h3>METHODS</h3><div>Pre-surgery in vivo and post-surgery ex vivo PCCT (Siemens Naeotom Alpha, Siemens Healthineers, Germany) of the tibial plateau from participants with severe knee OA referred to arthroplasty surgery from January 2022 through September 2023 were compared. Acquisition/reconstruction details: a tube current of 120 kV, a matrix size of 1024 × 1024, a slice thickness of 0.2 mm, and a FOV of 150 × 150 mm. 18 in vivo/ex vivo PCCT pairs were included. The ex vivo scans was registered to the in vivo scans. Linear regression and Bland-Altman plots were used to assess correlation and agreement between in vivo and ex vivo measures of bone volume fraction (BV/TV), trabecular thickness (Tb.Th.), and attenuation in healthy and sclerotic trabecular bone. Delineated areas of bone sclerosis were compared using the Dice coefficient and Hausdorff distance, Fig. 1.</div></div><div><h3>RESULTS</h3><div>Comparing in vivo and ex vivo scans strong correlations were found for BV/TV, R<sup>2</sup>=0.82 and attenuation in both healthy, R<sup>2</sup>=0.89, and sclerotic, R<sup>2</sup>=0.79, bone, while a moderate correlation was found for Tb.Th., R<sup>2</sup>=0.55. Bias for BV/TV and Tb.Th. was -4.1% and -0.598mm, respectively, and -41.4 HU and -81.1 HU for healthy and sclerotic bone, respectively. A proportional bias was observed for BV/TV and Tb.Th., Fig. 2. There was excellent agreement between the segmentations of sclerotic areas, Dice coefficient = 0.91 and Hausdorff distance = 0.11mm.</div></div><div><h3>CONCLUSION</h3><div>In patients with severe knee OA, BV/TV and attenuation can be obtained with high correlation and small bias between in vivo and ex vivo scans. Tb.Th. showed moderate correlation and larger bias. Subchondral bone sclerosis, a key OA feature, is well translated from ex vivo to in vivo PCCT. Longitudinal studies using in vivo PCCT are feasible, but caution may be advised when measuring Tb.Th.</div></div>","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"REVEALING EARLY SUBCHONDRAL BONE STRUCTURAL CHANGES IN OSTEOARTHRITIS PROGRESSION IN A COLLAGENASE-INDUCED MOUSE MODEL USING MICRO COMPUTED TOMOGRAPHY","authors":"H. Liu, Z. Li, C.E. Davey, K.S. Stok","doi":"10.1016/j.ostima.2025.100301","DOIUrl":"10.1016/j.ostima.2025.100301","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>The deployment of micro-computed tomography (microCT) enables quantitative morphometric analysis (QMA) to quantify morphological and structural changes caused by OA in mouse knee joint with excellent spatial resolution. Previous studies quantifying microstructural changes to subchondral tibiae in fortnightly intervals, report bone loss and trabecular thinning as early as two weeks post disease induction in mouse models. However, evidence suggests that the subchondral bone turnover may occur earlier than two weeks post disease induction in a mouse OA model.</div></div><div><h3>OBJECTIVE</h3><div>To reveal early bone microstructural changes associated with OA progression in a mouse model with a high temporal resolution using microCT and QMA.</div></div><div><h3>METHODS</h3><div>Seventy-five male C57BL/10 mice aged nine weeks were recruited and randomly assigned to three cross-sectional cohorts, i.e., baseline (n = 4), control (n = 24) and OA (n = 47) cohorts. Forty-seven ten-week-old mice assigned to OA cohort received intra-articular injection of 10 unit of filtered collagenase dissolved in 6 µl physiological saline to the right joints (OA group) through the patellar ligament. A similar volume of saline was intraarticularly injected to the left contralateral joints (CTLR group). Prior to scanning, mice were euthanized at 0-, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8-weeks post ten-week-old. Scans were performed using microCT (vivaCT80, SCANCO Medical AG, Brüttisellen, Switzerland) with a source voltage of 70 kVp, an integration time of 350 <em>ms</em>, a current of 114 µA, a nominal resolution of 10.4 µm, and 500 projections with each scan taking around 20 minutes. QMA was performed to quantify changes to subchondral bone microstructure associated with OA progression. To detect differences between treatments at each time point, a linear mixed-effect model was used. Individual mice were considered as random effects, time points (1- to 8- weeks post collagenase injection) and treatment (CT, CTLR, and OA) were considered as fixed effects.</div></div><div><h3>RESULTS</h3><div>Representative segmented microCT images from CT and OA group can be found in <strong>Figure 1 A</strong>. Typical osteoarthritic characteristics were observed in OA group at multiple time points, with changes detectable as early as one week post disease induction, shown in <strong>Figure 1 B</strong>. Specifically, comparing joints from CT and CTLR groups, smaller trabecular thickness, Tb.Th, were observed at both lateral and medial sides in OA femora, in accordance with the increasing trabecular spacing, Tb.Sp, and decreasing trabecular number, Tb.N.</div></div><div><h3>CONCLUSION</h3><div>This study, for the first time, demonstrated that prominent bone changes could be detected as early as one week after disease induction. These findings underscore the necessity of early quantification to capture rapidly changing bone microstructure alterations in early s","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100301"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}