V. Peitso, S. Das Gupta, S. Kauppinen, M. Risteli, M. Finnilä, A. Mobasheri
{"title":"HIGH-RESOLUTION 3D IMAGING OF BOVINE TAIL INTERVERTEBRAL DISC DEGENERATION USING IODINE-ENHANCED X-RAY MICROSCOPY","authors":"V. Peitso, S. Das Gupta, S. Kauppinen, M. Risteli, M. Finnilä, A. Mobasheri","doi":"10.1016/j.ostima.2025.100307","DOIUrl":"10.1016/j.ostima.2025.100307","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>The vertebral endplates of the intervertebral disc (IVD) consist of two structurally distinct layers: the cartilaginous endplate (CEP) and the bony endplate (BEP). While most research on IVD degeneration has focused on the biochemical or biomechanical failures of the annulus fibrosus (AF) and nucleus pulposus (NP), the physiology and microstructure of the CEP have often been overlooked. To address this gap, we employed iodine-enhanced X-ray microscopy (XRM) in a bovine tail IVD degeneration model. This approach enabled the simultaneous visualization of soft and hard tissues, with a specific focus on the CEP.</div></div><div><h3>OBJECTIVE</h3><div>1) To simultaneously visualize soft and hard tissues in IVDs, with a specific focus on detecting changes in the CEP using iodine-enhanced XRM. 2) To validate the observed structural changes through histological analysis.</div></div><div><h3>METHODS</h3><div>34 IVDs with intact vertebral endplates were harvested from six fresh bovine tails. Samples were cultured in Dulbecco’s Modified Eagle Medium (DMEM) for 11 days under unloaded conditions. On day one, approximately 70-100 μL of chondroitinase ABC (chABC, 0.5 U/mL), a pro-inflammatory cytokine cocktail containing interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) (each at 100 ng/mL), or a sham control solution of phosphate-buffered saline (PBS) with 0.1% bovine serum albumin (BSA) was injected into the NP using a 21G needle. Additional control samples received no injection. On day 11, IVDs were fixed in 4% formaldehyde and dehydrated. Samples were immersed in 1% (w/v) iodine (I<sub>2</sub>) in 100% ethanol and stained for a minimum of two weeks. Following staining, samples were washed, embedded in 1% agarose, and imaged with an XRM (Zeiss Xradia Versa 610; source voltage: 60kV; exposure: 4-6 sec; voxel size: 9.9-15.6 µm). Post-imaging, iodine was removed, and samples were decalcified and paraffin-embedded. Thin sections (7-10 µm) were prepared and stained with hematoxylin and eosin (H&E) and safranin-O and fast green. Reconstituted XRM image stacks were processed using built-in noise filtering software (Zeiss). Dragonfly 3D world (Comet) software was used for visualization and segmentation. XRM images were qualitatively compared with histological sections to assess changes in soft and hard tissues (Figures 1 and 2).</div></div><div><h3>RESULTS</h3><div>The interface between mineralized and non-mineralized cartilage (tidemark) was visualized using XRM, enabling the identification of calcified cartilage and CEP (Figure 1). Iodine-based contrast provided sufficient resolution to detect structural malalignments among the BEP, CEP, and NP (Figure 2). Notably, even sham injections with PBS induced degenerative changes in the disc.</div></div><div><h3>CONCLUSION</h3><div>Non-destructive iodine-enhanced XRM enables clear visualization of the CEP, providing sufficient contrast to simultaneously assess structural cha","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100307"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524132","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}
V.P. Karjalainen , I. Hellberg , A. Turkiewicz , B. Shakya , N. Khoshimova , E. Nevanranta , K. Elkhouly , S. Das Gupta , A. Sjögren , M.A.J. Finnilä , P. Önnerfjord , V. Hughes , J. Tjörnstrand , M. Englund , S. Saarakkala
{"title":"EX VIVO IMAGING OF DIFFERENT CALCIFICATION TYPES IN POSTERIOR HORN OF HUMAN MENISCUS USING MICRO-COMPUTED TOMOGRAPHY","authors":"V.P. Karjalainen , I. Hellberg , A. Turkiewicz , B. Shakya , N. Khoshimova , E. Nevanranta , K. Elkhouly , S. Das Gupta , A. Sjögren , M.A.J. Finnilä , P. Önnerfjord , V. Hughes , J. Tjörnstrand , M. Englund , S. Saarakkala","doi":"10.1016/j.ostima.2025.100296","DOIUrl":"10.1016/j.ostima.2025.100296","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Meniscal calcifications are known to be associated with OA. Specifically, two types of calcifications have been commonly identified in osteoarthritic knees: basic calcium phosphate (BCP) and calcium pyrophosphate (CPP). However, their pathological significance remains largely unclear. Characterizing differences between the calcification types and their deposition patterns inside the meniscus could help in their identification with <em>in vivo</em> imaging modalities and provide a better understanding of the role of meniscal calcifications in the OA disease process.</div></div><div><h3>OBJECTIVE</h3><div>1) Identify the two different types of calcifications in human meniscus <em>ex vivo</em> in 3D using µCT; 2) Describe the different deposition patterns observed in BCP and CPP calcifications.</div></div><div><h3>METHODS</h3><div>From the MENIX biobank in Lund, Sweden, we collected 82 posterior horns of medial and lateral menisci from 20 total knee replacement (TKR) patients and 21 deceased donors (50/50% female/male, average age 71 years) for the study. A 5-mm-thick subsection was dissected from the posterior horn, fixed in formalin, dehydrated, and treated with hexamethyldisilazane (HMDS) before air-drying at room temperature overnight. Subsequently, the HMDS-treaded section was imaged with a desktop µCT imaging (SkyScan 1272, Bruker, micro-CT) with the following settings: 60 kV, 166 µA, 2.0 µm voxel size, 3500 ms exposure time, random movement 25 voxels, and without an additional filter. Two different image reconstruction settings were used to maximize the image quality of meniscal soft tissue and calcifications. Pieces of meniscus adjacent to the µCT underwent histological processing and Alizarin Red staining. Calcification types from the histological sections were identified using Raman micro-spectroscopy.</div></div><div><h3>RESULTS</h3><div>We successfully imaged both meniscal calcification types together with soft tissue in 3D using high-resolution µCT (Figure 1). Based on Raman spectral analysis, out of the 82 menisci, 39 had at least one calcification: 28 had BCP calcifications, 8 had CPP calcifications, and 3 had both. In µCT, BCP calcifications were quantitatively denser, morphologically sharper, more punctuated, smaller in size as well as number, and more spherical than CPPs. Unlike CPPs, BCPs were mainly deposited in the periphery of meniscal tissue, inside complex 3D tears or fibrillations. In contrast, the CPP calcifications formed long rod-like structures, mainly inside the meniscal tissue.</div></div><div><h3>CONCLUSION</h3><div>Based on the 3D µCT images, BCP calcifications were not found inside the meniscal tissue but in the peripheral area. This could suggest that larger clusters of BCP calcifications found in the meniscus come from the synovial fluid and possibly originate from articular cartilage or bone. Meanwhile, the likely place for CPPs to accumulate and expand within the meniscal tissue is","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524184","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}
H. Harandi , F.W. Roemer , S. Mastbergen , J. Collins , A. Guermazi , C.K. Kwoh , T. Neogi , M. Loggia , R. Edwards , E. Duscova , M. Kloppenburg , F.J. Blanco , I.K. Haugen , F. Berenbaum , M.P. Jansen , M. Jarraya
{"title":"PAIN PHENOTYPE AS AN EFFECT MODIFIER: EXPLORING THE ROLE OF PAIN-DETECT IN THE ASSOCIATION BETWEEN WOMAC SCORES AND MRI-DETECTED STRUCTURAL DAMAGE","authors":"H. Harandi , F.W. Roemer , S. Mastbergen , J. Collins , A. Guermazi , C.K. Kwoh , T. Neogi , M. Loggia , R. Edwards , E. Duscova , M. Kloppenburg , F.J. Blanco , I.K. Haugen , F. Berenbaum , M.P. Jansen , M. Jarraya","doi":"10.1016/j.ostima.2025.100289","DOIUrl":"10.1016/j.ostima.2025.100289","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>A fundamental challenge in treating patients with OA is the discordance between pain and structural abnormalities, reflecting the fact that numerous factors outside of joint pathology can contribute to the pain experience. Thus, pain in OA represents different phenotypes, including nociceptive and neuropathic-like pain. The Pain-DETECT (PD-Q) can be used to help distinguish between the two, with lower PD-Q scores suggesting nociceptive pain. While associations between different MRI-based MOAKS measures and traditional pain outcomes (such as WOMAC) have been reported, whether those associations are modified by pain phenotype (as assessed by PD-Q) is not known.</div></div><div><h3>OBJECTIVE</h3><div>To test whether the association between WOMAC scores and MRI-detected OA structural pathology is modified by PD-Q score.</div></div><div><h3>METHODS</h3><div>We performed a pooled cross-sectional analysis with repeated measures using data from all 4 visits of the IMI-APPROACH cohort (baseline, 6-, 12-, and 24-months), where participants were administered the total WOMAC and PD-Q. For each participant, an index knee with OA was selected based on ACR clinical criteria. MRI of the index knee was obtained for all participants and visits, and scored using MOAKS, including bone marrow lesions (BML); Hoffa’s synovitis and effusion-synovitis. WOMAC scores ranged from 0-96. Participants with no symptoms or functional limitation (WOMAC = 0) were excluded to avoid floor effect. <strong>We conducted the analysis in 3 steps: Step 1:</strong> We fit linear mixed-effects models with random intercepts for each participant to account for multiple observations per participant and included a MOAKS × PD-Q interaction term to test for effect modification. The MOAKS features we tested included: presence of full-thickness cartilage loss, presence of osteophytes ≥ grade 2, total number of BML, sum of total scores of BML, presence of BML ≥ grade 2, presence of effusion ≥grade 2 and grade 3 separately, presence of synovitis ≥ grade 2 and grade 3 separately, presence of any meniscus tear. <strong>Step 2:</strong> for each MOAKS measure identified as significant in step 1 (using a liberal threshold of p<0.2) we conducted a Johnson–Neyman (J-N) analysis to locate PD-Q regions where the conditional association between MOAKS and square root of WOMAC (sqrtWOMAC) changed from being statistically significant (using the 95% CI) to non-significant. <strong>Step 3:</strong> for each MOAKS measure identified in step 1, we stratified the cohort into two PD-Q subgroups (at the J-N cutoff identified in step 2) and refitted stratified linear mixed-effects models to estimate the MOAKS–sqrtWOMAC association within each subgroup.</div></div><div><h3>RESULTS</h3><div>We included 287 participants (mean age 66.5 (SD=7.2), 77.7% female, mean/median PD-Q score 9.36 / 9), who contributed 949 observations. Significant effect modification was observed for sum of BML siz","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522429","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":"FEASIBILITY OF NON-CONTRAST MRI TO DETECT CHANGES IN SYNOVITIS AFTER ACL RECONSTRUCTION SURGERY","authors":"F. Kogan , K. Stevens , A. Williams , C. Chu","doi":"10.1016/j.ostima.2025.100298","DOIUrl":"10.1016/j.ostima.2025.100298","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Synovitis is a recognized risk factor for post-traumatic osteoarthritis post-ACL reconstruction (ACLR). The reference standard for imaging synovitis is contrast enhanced MRI, but this adds time and cost and may be contraindicated in some patients, which may limit evaluation of this important finding. Recently, several non-contrast MRI methods have shown strong agreement with CE-MRI for semiquantitative assessment of synovitis.</div></div><div><h3>OBJECTIVE</h3><div>To evaluate the feasibility of quantitative double-echo in steady-state (qDESS) as a non-contrast MR technique to detect changes in synovitis in patients pre- and post-ACLR.</div></div><div><h3>METHODS</h3><div>14 males and 4 females (age:27±6 years, BMI:24±3 kg/m<sup>2</sup>) with ACL tears underwent ACLR surgery (mean time from injury to surgery 10±5 weeks) and were scanned on a 3T MR scanner at three timepoints: (1) baseline post ACL tear but before reconstruction, (2) 6-weeks and (3) 6-months after ACLR. At each time point, a 3D qDESS acquisition was performed with parameters: TR/TE1/TE2 = 20.5/6.4/34.6 ms; acquisition resolution = 0.4 × 0.4 × 1.5 mm<sup>3</sup>; 80 slices; Flip Angle = 20. qDESS synovitis hybrid images were created by a weighted subtraction of the 2<sup>nd</sup> echo signal from the 1<sup>st</sup> echo to null signal from joint fluid in order to provide contrast to the synovium. Synovitis was scored in the knee overall and in 4 regional locations by a blinded radiologist on a scale of 0-3 (0 = none to 3 = severe).</div></div><div><h3>RESULTS</h3><div>Figure 1 shows a representative case of qDESS synovitis-weighted hybrid images at the three timepoints and their corresponding scores. Figure 2a shows a table of the % of patients (out of 18) that were scored to have improved or worsened synovitis between baseline and 6-weeks post-ACLR and between 6-weeks and 6-months post-ACLR. Overall, there was a clear trend towards synovitis worsening 6-weeks after ACLR and then improving between 6-weeks and 6-months post-surgery. Furthermore, when the 6-week and 6-month timepoints for each patient were compared directly but blinded to order, an improvement in assessed synovitis was observed in a further 82% of overall impressions that were previously scored as no change in blinded and randomized assessments (Figure 2b). Repeated synovitis scoring assessments showed very strong agreement (Gwets AC2>0.80) in overall and sub-region assessments.</div></div><div><h3>DISCUSSION</h3><div>While ground-truth synovitis measures were not available, the qDESS hybrid method was able to detect both worsening synovitis that is expected after ACLR surgery and improvement in synovitis that is expected during the following 5 months of recovery. The lack of differentiation of synovitis changes between timepoints may partly be attributed to the coarseness of the 4-point semi-quantitative Likert-scale which is based on synovial hypertrophy and nodularity In overall a","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521548","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}
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}
{"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}
E. Nevanranta , V.-P. Karjalainen , M. Brix , I. Hellberg , A. Turkiewicz , B. Shakya , P. Önnerfjord , S. Ylisiurua , A. Sjögren , K. Elkhouly , V. Hughes , J. Tjörnstrand , S. Saarakkala , M. Englund , M.A.J. Finnilä
{"title":"CHARACTERIZING MENISCAL CALCIFICATIONS WITH PHOTON COUNTING-BASED DUAL-ENERGY COMPUTED TOMOGRAPHY","authors":"E. Nevanranta , V.-P. Karjalainen , M. Brix , I. Hellberg , A. Turkiewicz , B. Shakya , P. Önnerfjord , S. Ylisiurua , A. Sjögren , K. Elkhouly , V. Hughes , J. Tjörnstrand , S. Saarakkala , M. Englund , M.A.J. Finnilä","doi":"10.1016/j.ostima.2025.100303","DOIUrl":"10.1016/j.ostima.2025.100303","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Meniscal calcifications, including basic calcium phosphate (BCP) and calcium pyrophosphate (CPP), are commonly associated with OA and may disrupt meniscal function, contributing to joint degeneration. However, the role of specific calcification types in OA is not fully understood due to the lack of non-invasive imaging techniques that can differentiate them <em>in vivo</em>. While Raman spectroscopy accurately distinguishes BCP from CPP, it is limited to 2D and requires destructive histological processing. In contrast, dual-energy computed tomography (DECT) has shown potential for differentiating calcifications in both <em>in vivo</em> and <em>ex vivo</em>, but its performance varies across previous studies. The integration of photon-counting detectors (PCD) in CT imaging improves spatial resolution and enables multi-energy acquisition, enhancing <em>in vivo</em> calcification characterization.</div></div><div><h3>OBJECTIVE</h3><div>We evaluated the capability of dual-energy computed tomography with a photon counting detector (PCD-DECT) to differentiate BCP and CPP calcification deposits in the posterior horns of human menisci <em>ex vivo</em>, using Raman spectroscopy as the reference.</div></div><div><h3>METHODS</h3><div>This study included 82 medial and lateral meniscus samples from 21 deceased donors without known knee OA and 20 TKR patients with medial compartment OA. Samples were imaged using an experimental cone-beam CT setup with PCD, operating at 120 kVp and 0.2 mA. Low energy (LE) data were collected in the 20-50 keV range, and high energy (HE) data in the 50-120 keV range, with a final voxel size of 37 µm. Only calcified samples identified using Raman spectroscopy (n = 36), 8 CPP and 28 BCP samples, were included to the analysis. Calcifications were segmented and divided between BCP and CPP groups. Subsequently, LE, HE, and Dual Energy Index (DEI) values were measured for each calcification. We used linear mixed models to estimate associations between LE and HE variables and the calcification type, and to compare the DEI values between the calcification types. Estimates are presented with 95% confidence intervals.</div></div><div><h3>RESULTS</h3><div>Figure 1A-C shows a 3D visualization of menisci with and without different calcifications. The results showed that CPP calcifications had consistently lower LE values than BCP for corresponding HE values. The difference increased with higher HE values, peaking at 500 HU with a difference of 166.1 HU (95% CI: 73.4, 258.8), while the smallest difference occurs at -100 HU, where the difference is 33.81 HU (95% CI: -40.38, 107.99) HU. The differences between LE and HE values are shown in Figure 1D-E. Additionally, estimated mean DEI values were higher in BCP calcifications compared to CPP, with an estimated difference of 0.035 (95%CI: 0.011, 0.059). Detailed results are shown in Table 1.</div></div><div><h3>CONCLUSION</h3><div>Our findings show that BCP and CPP m","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100303"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524188","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}
Z. Zhou , X. He , Y. Hu , H.A. Khan , F. Liu , M. Jarraya
{"title":"AUTOMATED QUANTIFICATION OF MENISCUS EXTRUSION IN MRI VIA AI FOUNDATION MODEL: PROOF OF CONCEPT USING A TRAINING-FREE FEW-SHOT SEGMENTATION APPROACH","authors":"Z. Zhou , X. He , Y. Hu , H.A. Khan , F. Liu , M. Jarraya","doi":"10.1016/j.ostima.2025.100333","DOIUrl":"10.1016/j.ostima.2025.100333","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Manual assessment of meniscus extrusion (ME) in magnetic resonance (MR) images is time-consuming and prone to variability, limiting efficiency in clinical and research settings. While deep learning methods have shown promise in MR image segmentation, their reliance on task-specific training and large annotated datasets limits scalability and adaptability.</div></div><div><h3>OBJECTIVE</h3><div>Building upon our previously developed AI foundation model, we aim to establish a fully automated pipeline for quantifying ME in knee MRI with our model training and eliminate the need for large annotated datasets.</div></div><div><h3>METHODS</h3><div>By providing a support set including a minimal number of segmentation examples, the AI Foundation Model enables accurate segmentation of knee anatomy and reliable ME measurement in a training-free, few-shot manner. In the study, we analyzed 3T MR images acquired using either T2-weighted or proton density MR sequences from 10 patients with mild osteoarthritis. Manual segmentations of femur, tibia, medial, and lateral menisci were performed by experts. Two patients, one with T2-weighted and one with proton density images, were randomly selected to build the support set. The remaining 8 patients comprised the testing set, which was used for both automated segmentation and model evaluation. Segmentation performance was assessed using the Dice Coefficient. For ME evaluation, an experienced radiologist manually identified the slice containing the tibial spine and measured extrusion as the reference. Automated ME measurement was computed from the segmentation by detecting the femoral condyle and tibial plateau edge, then measuring the distance from the most medial point of the medial meniscus to a reference line connecting the femoral condyle and tibial plateau edge.</div></div><div><h3>RESULTS</h3><div>The average Dice Coefficient was 94.07 ± 3.97% for the femur, 97.09 ± 0.93% for the tibia, 82.91 ± 6.72% for the medial meniscus, and 85.49 ± 5.24% for the lateral meniscus. ME measurements predicted by the model were also compared with ground truth values. The human measured ME was 4.26 ± 1.46 mm, while the model-predicted ME was 4.18 ± 1.16 mm.</div></div><div><h3>CONCLUSION</h3><div>This study demonstrates that the foundation model enables reliable and fully automated quantification of meniscus extrusion from knee MR images without requiring training or large annotated datasets. With only two support examples, the model achieved accurate segmentation and ME measurement across eight testing subjects, underscoring its efficiency and strong generalization. Its consistent performance across key anatomical structures highlights its potential for expert-level evaluation in both clinical and research settings with minimal manual effort. Further work will explore semi-automated expansion of the support set and extension to diverse MRI protocols and osteoarthritis severities, and validation on","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100333"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524261","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}
J.T. Harvey , T.E. McAlindon , J. Baek , J. MacKay , M. Zhang , G.H. Lo , S.-H. Liu , C.B. Eaton , M.S. Harkey , J.C. Patarini , J.B. Driban
{"title":"FROM MENISCAL DEGENERATION TO OSTEOARTHRITIS: TRACKING EARLY DISEASE PROGRESSION WITH MRI-BASED COMPOSITE SCORES: DATA FROM THE OSTEOARTHRITIS INITIATIVE","authors":"J.T. Harvey , T.E. McAlindon , J. Baek , J. MacKay , M. Zhang , G.H. Lo , S.-H. Liu , C.B. Eaton , M.S. Harkey , J.C. Patarini , J.B. Driban","doi":"10.1016/j.ostima.2025.100290","DOIUrl":"10.1016/j.ostima.2025.100290","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Meniscal degeneration predisposes knees without radiographic OA to develop a future meniscal tear and an accelerated onset and progression of OA. Understanding the relationship between meniscal degeneration and OA-related biomarkers in knees without radiographic OA is essential for improving early detection, monitoring disease progression, and developing intervention strategies to prevent or slow the progression of this debilitating condition.</div></div><div><h3>OBJECTIVE</h3><div>To explore the relationship between meniscal degeneration (intrameniscal signal alteration without a tear) and future OA pathology measured by composite scores based on MRI: disease activity (BM lesion and effusion-synovitis volumes) and cumulative damage (articular cartilage damage).</div></div><div><h3>METHODS</h3><div>Our sample included 225 participants from the OAI with intact menisci (defined as normal or meniscal degeneration without tear) on MRI and no radiographic knee OA at baseline. There were 110 participants with normal menisci (77% Female, 55 [SD 7] average years of age) and 115 with meniscal degeneration (60% Female, 61 [SD 9] average years of age). We used longitudinal MRIs from an existing study to calculate disease activity and cumulative damage. Negative values represent milder disease activity or cumulative damage than the average of a reference sample, among whom 93% had moderate-severe radiographic knee osteoarthritis (KLG = 3 or 4), and the average WOMAC knee pain score was 5.0 (SD=3.6). MR images were collected at each OAI site using Siemens 3.0 Tesla Trio MR systems and knee coils. Acquisitions included a sagittal IM fat-suppressed sequence (field of view=160mm, slice thickness=3mm, skip=0mm, flip angle=180 degrees, echo time=30ms, recovery time=3200ms, 313 × 448 matrix, x-resolution=0.357mm, y-resolution=0.357mm), which was used to measure BML and effusion-synovitis volumes. Cartilage damage was quantified using a 3D DESS sequence: field of view=140mm, slice thickness=0.7mm, skip=0mm, flip angle=25 degrees, echo time=4.7ms, recovery time=16.3ms, 307 × 384 matrix, x-resolution=0.365mm, y-resolution=0.365mm. We used robust regression models with M estimation and Huber weights to assess the association between baseline meniscal degeneration (exposure) and disease activity or cumulative damage at baseline and four annual follow-up visits (outcomes), adjusting for gender, race, age, static alignment, and body mass index.</div></div><div><h3>RESULTS</h3><div>Knees with meniscal degeneration were more likely to have, on average, 0.21 greater disease activity at 12 months than knees with normal menisci (parameter estimate=0.21, 95% confidence interval [CI]=0.09, 0.33); this association persisted over time. The association between meniscal degeneration and cumulative damage only became statistically significant at the 48-month visit (parameter estimate=0.74, 95% CI=0.18, 1.31).</div></div><div><h3>CONCLUSION</h3><div>This","PeriodicalId":74378,"journal":{"name":"Osteoarthritis imaging","volume":"5 ","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522430","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}