CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis.

Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition. Biopsy-based single-cell RNA-sequencing analyses in experimental arthritis show that FAP signal reduction reflects a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalization) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalization). Spatial transcriptomics of human joints indicates that pro-resolving niches of CD200+DKK3+ fibroblasts cluster with type 2 innate lymphoid cells, whereas MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid cell phenotype and induced resolution of arthritis via CD200-CD200R1 signaling. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

How AI May Transform Musculoskeletal Imaging.

While musculoskeletal imaging volumes are increasing, there is a relative shortage of subspecialized musculoskeletal radiologists to interpret the studies. Will artificial intelligence (AI) be the solution? For AI to be the solution, the wide implementation of AI-supported data acquisition methods in clinical practice requires establishing trusted and reliable results. This implementation will demand close collaboration between core AI researchers and clinical radiologists. Upon successful clinical implementation, a wide variety of AI-based tools can improve the musculoskeletal radiologist's workflow by triaging imaging examinations, helping with image interpretation, and decreasing the reporting time. Additional AI applications may also be helpful for business, education, and research purposes if successfully integrated into the daily practice of musculoskeletal radiology. The question is not whether AI will replace radiologists, but rather how musculoskeletal radiologists can take advantage of AI to enhance their expert capabilities.

Erosive hand osteoarthritis and sarcopenia: data from Osteoarthritis Initiative cohort.

OBJECTIVES: There is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study pioneers the exploration of the association between EHOA and sarcopenia, both of which are predominantly observed in the older adults. METHODS: Using the Osteoarthritis Initiative cohort, we selected hand OA (modified Kellgren and Lawrence (grade ≥2 in ≥1 hand joint) participants with radiographic central erosions in ≥1 joints (EHOA group) and propensity score-matched hand OA participants with no erosion (non-EHOA group). MRI biomarkers of thigh muscles were measured at baseline, year 2 and year 4 using a validated deep-learning algorithm. To adjust for 'local' effects of coexisting knee OA (KOA), participants were further stratified according to presence of radiographic KOA. The outcomes were the differences between EHOA and non-EHOA groups in the 4-year rate of change for both intramuscular adipose tissue (intra-MAT) deposition and contractile (non-fat) area of thigh muscles. RESULTS: After adjusting for potential confounders, 844 thighs were included (211 EHOA:633 non-EHOA; 67.1±7.5 years, female/male:2.9). Multilevel mixed-effect regression models showed that EHOA is associated a different 4-year rate of change in intra-MAT deposition (estimate, 95% CI: 71.5 mm2/4 years, 27.9 to 115.1) and contractile area (estimate, 95% CI: -1.8%/4 years, -2.6 to -1.0) of the Quadriceps. Stratified analyses showed that EHOA presence is associated with adverse changes in thigh muscle quality only in participants without KOA. CONCLUSIONS: EHOA is associated with longitudinal worsening of thigh muscle composition only in participants without concomitant KOA. Further research is needed to understand the systemic factors linking EHOA and sarcopenia, which unlike EHOA is modifiable through specific interventions.

Osteoarthritis year in review 2023: Imaging.

PURPOSE: This narrative review summarizes the original research in the field of in vivo osteoarthritis (OA) imaging between 1 January 2022 and 1 April 2023. METHODS: A PubMed search was conducted using the following several terms pertaining to OA imaging, including but not limited to "Osteoarthritis / OA", "Magnetic resonance imaging / MRI", "X-ray" "Computed tomography / CT", "artificial intelligence /AI", "deep learning", "machine learning". This review is organized by topics including the anatomical structure of interest and modality, AI, challenges of OA imaging in the context of clinical trials, and imaging biomarkers in clinical trials and interventional studies. Ex vivo and animal studies were excluded from this review. RESULTS: Two hundred and forty-nine publications were relevant to in vivo human OA imaging. Among the articles included, the knee joint (61%) and MRI (42%) were the predominant anatomical area and imaging modalities studied. Marked heterogeneity of structural tissue damage in OA knees was reported, a finding of potential relevance to clinical trial inclusion. The use of AI continues to rise rapidly to be applied in various aspect of OA imaging research but a lack of generalizability beyond highly standardized datasets limit interpretation and wide-spread application. No pharmacologic clinical trials using imaging data as outcome measures have been published in the period of interest. CONCLUSIONS: Recent advances in OA imaging continue to heavily weigh on the use of AI. MRI remains the most important modality with a growing role in outcome prediction and classification.

A perspective on the evolution of semi-quantitative MRI assessment of osteoarthritis: Past, present and future.

OBJECTIVE: This perspective describes the evolution of semi-quantitative (SQ) magnetic resonance imaging (MRI) in characterizing structural tissue pathologies in osteoarthritis (OA) imaging research over the last 30 years. METHODS: Authors selected representative articles from a PubMed search to illustrate key steps in SQ MRI development, validation, and application. Topics include main scoring systems, reading techniques, responsiveness, reliability, technical considerations, and potential impact of artificial intelligence (AI). RESULTS: Based on original research published between 1993 and 2023, this article introduces available scoring systems, including but not limited to Whole-Organ Magnetic Resonance Imaging Score (WORMS) as the first system for whole-organ assessment of the knee and the now commonly used MRI Osteoarthritis Knee Score (MOAKS) instrument. Specific systems for distinct OA subtypes or applications have been developed as well as MRI scoring instruments for other joints such as the hip, the fingers or thumb base. SQ assessment has proven to be valid, reliable, and responsive, aiding OA investigators in understanding the natural history of the disease and helping to detect response to treatment. AI may aid phenotypic characterization in the future. SQ MRI assessment's role is increasing in eligibility and safety evaluation in knee OA clinical trials. CONCLUSIONS: Evidence supports the validity, reliability, and responsiveness of SQ MRI assessment in understanding structural aspects of disease onset and progression. SQ scoring has helped explain associations between structural tissue damage and clinical manifestations, as well as disease progression. While AI may support human readers to more efficiently perform SQ assessment in the future, its current application in clinical trials still requires validation and regulatory approval.

Thigh muscle composition changes in knee osteoarthritis patients during weight loss: Sex-specific analysis using data from osteoarthritis initiative.

OBJECTIVES: Sex of patients with knee osteoarthritis (KOA) may impact changes in thigh muscle composition during weight loss, the most well-known disease-modifying intervention. We investigated longitudinal sex-based changes in thigh muscle quality during weight loss in participants with KOA. METHODS: Using Osteoarthritis Initiative (OAI) cohort data, we included females and males with baseline radiographic KOA who experienced > 5 % reduction in Body Mass Index (BMI) over four years. Using a previously validated deep-learning algorithm, we measured Magnetic Resonance Imaging (MRI)-derived biomarkers of thigh muscles at baseline and year-4. Outcomes were the intra- and inter-muscular adipose tissue (Intra-MAT and Inter-MAT) and contractile percentage of thigh muscles between females and males. The analysis adjusted for potential confounders, such as demographics, risk factors, BMI change, physical activity, diet, and KOA status. RESULTS: A retrospective selection of available thigh MRIs from KOA participants who also had a 4-year weight loss (>5 % of BMI) yielded a sample comprising 313 thighs (192 females and 121 males). Female and male participants exhibited a comparable degree of weight loss (females: -9.72 ±â€¯4.38, males: -8.83 ±â€¯3.64, P-value=0.060). However, the changes in thigh muscle quality were less beneficial for females compared to males, as shown by a less degree of longitudinal decrease in Intra-MAT (change difference,95 %CI: 783.44 mm2/4-year, 505.70 to 1061.19, P-value<0.001) and longitudinal increase in contractile percentage (change difference,95 %CI: -3.9 %/4-year, -6.5 to -1.4, P-value=0.019). CONCLUSIONS: In participants with KOA and 4-year weight loss, the longitudinal changes in thigh muscle quality were overall beneficial but to a less degree in females compared to males. Further research is warranted to investigate the underlying mechanisms and develop sex-specific interventions to optimize muscle quality during weight loss.

Primary anterior cruciate ligament repair-morphological and quantitative assessment by 7-T MRI and clinical outcome after 1.5 years.

OBJECTIVES: The purpose of this study was to assess morphological and quantitative changes of the anterior cruciate ligament (ACL) and cartilage after ACL repair. METHODS: 7T MRI of the knee was acquired in 31 patients 1.5 years after ACL repair and in 13 controls. Proton density-weighted images with fat saturation (PD-fs) were acquired to assess ACL width, signal intensity, elongation, and fraying. T2/T2* mapping was performed for assessment of ACL and cartilage. Segmentation of the ACL, femoral, and tibial cartilage was carried out at 12 ROIs. The outcome evaluation consisted of the Lysholm Knee Score and International Knee Documentation Committee (IKDC) subjective score and clinical examination. RESULTS: ACL showed a normal signal intensity in 96.8% and an increased width in 76.5% after repair. Fraying occurred in 22.6% without having an impact on the clinical outcome (Lysholm score: 90.39 ± 9.75, p = 0.76 compared to controls). T2 analysis of the ACL revealed no difference between patients and controls (p = 0.74). Compared to controls, assessment of the femoral and tibial cartilage showed a significant increase of T2* times in all ROIs, except at the posterolateral femur. Patients presented a good outcome in clinical examination with a Lysholm score of 87.19 ± 14.89 and IKDC of 80.23 ± 16.84. CONCLUSION: T2 mapping results suggest that the tissue composition of the ACL after repair is similar to that of a native ACL after surgery, whereas the ACL exhibits an increased width. Fraying of the ACL can occur without having any impact on functional outcomes. T2* analysis revealed early degradation at the cartilage. CLINICAL RELEVANCE STATEMENT: MRI represents a noninvasive diagnostic tool for the morphological and compositional assessment of the anterior cruciate ligament after repair, whereas knowledge about post-surgical alterations is crucial for adequate imaging interpretation. KEY POINTS: • There has been renewed interest in repairing the anterior cruciate ligament with a proximally torn ligament. • T2 times of the anterior cruciate ligament do not differ between anterior cruciate ligament repair patients and controls. • T2 mapping may serve as a surrogate for the evaluation of the anterior cruciate ligament after repair.

Imaging Biomarkers of Osteoarthritis.

Currently no disease-modifying osteoarthritis drug has been approved for the treatment of osteoarthritis (OA) that can reverse, hold, or slow the progression of structural damage of OA-affected joints. The reasons for failure are manifold and include the heterogeneity of structural disease of the OA joint at trial inclusion, and the sensitivity of biomarkers used to measure a potential treatment effect.This article discusses the role and potential of different imaging biomarkers in OA research. We review the current role of radiography, as well as advances in quantitative three-dimensional morphological cartilage assessment and semiquantitative whole-organ assessment of OA. Although magnetic resonance imaging has evolved as the leading imaging method in OA research, recent developments in computed tomography are also discussed briefly. Finally, we address the experience from the Foundation for the National Institutes of Health Biomarker Consortium biomarker qualification study and the future role of artificial intelligence.

Modern low-field MRI.

This narrative review explores recent advancements and applications of modern low-field (≤ 1 Tesla) magnetic resonance imaging (MRI) in musculoskeletal radiology. Historically, high-field MRI systems (1.5 T and 3 T) have been the standard in clinical practice due to superior image resolution and signal-to-noise ratio. However, recent technological advancements in low-field MRI offer promising avenues for musculoskeletal imaging. General principles of low-field MRI systems are being introduced, highlighting their strengths and limitations compared to high-field counterparts. Emphasis is placed on advancements in hardware design, including novel magnet configurations, gradient systems, and radiofrequency coils, which have improved image quality and reduced susceptibility artifacts particularly in musculoskeletal imaging. Different clinical applications of modern low-field MRI in musculoskeletal radiology are being discussed. The diagnostic performance of low-field MRI in diagnosing various musculoskeletal pathologies, such as ligament and tendon injuries, osteoarthritis, and cartilage lesions, is being presented. Moreover, the discussion encompasses the cost-effectiveness and accessibility of low-field MRI systems, making them viable options for imaging centers with limited resources or specific patient populations. From a scientific standpoint, the amount of available data regarding musculoskeletal imaging at low-field strengths is limited and often several decades old. This review will give an insight to the existing literature and summarize our own experiences with a modern low-field MRI system over the last 3 years. In conclusion, the narrative review highlights the potential clinical utility, challenges, and future directions of modern low-field MRI, offering valuable insights for radiologists and healthcare professionals seeking to leverage these advancements in their practice.

Comparison of 3T and 7T magnetic resonance imaging for direct visualization of finger flexor pulley rupture: an ex-vivo study.

OBJECTIVE: To compare image quality and diagnostic performance of 3T and 7T magnetic resonance imaging (MRI) for direct depiction of finger flexor pulleys A2, A3 and A4 before and after artificial pulley rupture in an ex-vivo model using anatomic preparation as reference. MATERIALS AND METHODS: 30 fingers from 10 human cadavers were examined at 3T and 7T before and after being subjected to iatrogenic pulley rupture. MRI protocols were comparable in duration, both lasting less than 22 min. Two experienced radiologists evaluated the MRIs. Image quality was graded according to a 4-point Likert scale. Anatomic preparation was used as gold standard. RESULTS: In comparison, 7T versus 3T had a sensitivity and specificity for the detection of A2, A3 and A4 pulley lesions with 100% vs. 95%, respectively 98% vs. 100%. In the assessment of A3 pulley lesions sensitivity of 7T was superior to 3T MRI (100% vs. 83%), whereas specificity was lower (95% vs. 100%). Image quality assessed before and after iatrogenic rupture was comparable with 2.74 for 7T and 2.61 for 3T. Visualization of the A3 finger flexor pulley before rupture creation was significantly better for 7 T (p < 0.001). Interobserver variability showed substantial agreement at 3T (κ = 0.80) and almost perfect agreement at 7T (κ = 0.90). CONCLUSION: MRI at 3T allows a comparable diagnostic performance to 7T for direct visualization and characterization of finger flexor pulleys before and after rupture, with superiority of 7T MRI in the visualization of the normal A3 pulley.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

OBJECTIVE: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. METHODS: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. RESULTS: After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45-79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: - 1.85 N/year, - 3.23 to - 0.47) and specific contractile force (- 0.04 N/cm2/year, - 0.07 to - 0.01), decreased thigh muscle contractile percent (- 0.03%/year, - 0.06 to - 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. CONCLUSIONS: Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care.

Advances in osteoarthritis imaging.

PURPOSE OF REVIEW: Imaging plays a pivotal role for diagnosis, follow-up and stratification of osteoarthritis patients in clinical trials and research. We aim to present an overview of currently available and emerging imaging techniques for osteoarthritis assessment and provide insight into relevant benefits and pitfalls of the different modalities. RECENT FINDINGS: Although radiography is considered sufficient for a structural diagnosis of osteoarthritis and is commonly used to define eligibility of patients for participation in clinical trials, it has inherent limitations based on the projectional nature of the technique and inherent challenges regarding reproducibility in longitudinal assessment. MRI has changed our understanding of the disease from 'wear and tear' of cartilage to a whole organ disorder. MRI assessment of structural changes of osteoarthritis includes semi-quantitative, quantitative and compositional evaluation. Ultrasound is helpful in evaluating the degree of synovitis and has value in the assessment particularly of the patella-femoral joint. Recent development of computed tomography technology including weight-bearing systems has led to broader application of this technology in a research context. SUMMARY: Advances in MRI technology have resulted in a significant improvement in understanding osteoarthritis as a multitissue disease.

Emerging Quantitative Imaging Techniques in Sports Medicine.

This article describes recent advances in quantitative imaging of musculoskeletal extremity sports injuries, citing the existing literature evidence and what additional evidence is needed to make such techniques applicable to clinical practice. Compositional and functional MRI techniques including T2 mapping, diffusion tensor imaging, and sodium imaging as well as contrast-enhanced US have been applied to quantify pathophysiologic processes and biochemical compositions of muscles, tendons, ligaments, and cartilage. Dual-energy and/or spectral CT has shown potential, particularly for the evaluation of osseous and ligamentous injury (eg, creation of quantitative bone marrow edema maps), which is not possible with standard single-energy CT. Recent advances in US technology such as shear-wave elastography or US tissue characterization as well as MR elastography enable the quantification of mechanical, elastic, and physical properties of tissues in muscle and tendon injuries. The future role of novel imaging techniques such as photon-counting CT remains to be established. Eventual prediction of return to play (ie, the time needed for the injury to heal sufficiently so that the athlete can get back to playing their sport) and estimation of risk of repeat injury is desirable to help guide sports physicians in the treatment of their patients. Additional values of quantitative analyses, as opposed to routine qualitative analyses, still must be established using prospective longitudinal studies with larger sample sizes.

Clinical Application of Ultrahigh-Field-Strength Wrist MRI: A Multireader 3-T and 7-T Comparison Study.

Background Ultrahigh-field-strength MRI at 7 T may permit superior visualization of noninflammatory wrist pathologic conditions, particularly due to its high signal-to-noise ratio compared with the clinical standard of 3 T, but direct comparison studies are lacking. Purpose To compare the subjective image quality of 3-T and 7-T ultrahigh-field-strength wrist MRI through semiquantitative scoring of multiple joint tissues in a multireader study. Materials and Methods In this prospective study, healthy controls and participants with chronic wrist pain underwent 3-T and 7-T MRI (coronal T1-weighted turbo spin-echo [TSE], coronal fat-suppressed proton-density [PD]-weighted TSE, transversal T2-weighted TSE) on the same day, from July 2018 to June 2019. Images were scored by seven musculoskeletal radiologists. The overall image quality, presence of artifacts, homogeneity of fat suppression, and visualization of cartilage, the triangular fibrocartilage complex (TFCC), and scapholunate and lunotriquetral ligaments were semiquantitatively assessed. Pairwise differences between 3 T and 7 T were assessed using the Wilcoxon signed-rank test. Interreader reliability was determined using the Fleiss kappa. Results In total, 25 healthy controls (mean age, 25 years ± 4 [SD]; 13 women) and 25 participants with chronic wrist pain (mean age, 39 years ± 16; 14 men) were included. Overall image quality (P = .002) and less presence of artifacts at PD-weighted fat-suppressed MRI were superior at 7 T. T1- and T2-weighted MRI were superior at 3 T (both P < .001), as was fat suppression (P < .001). Visualization of cartilage was superior at 7 T (P < .001), while visualization of the TFCC (P < .001) and scapholunate (P = .048) and lunotriquetral (P = .04) ligaments was superior at 3 T. Interreader reliability showed slight to substantial agreement for the detected pathologic conditions (κ = 0.20-0.64). Conclusion A 7-T MRI of the wrist had potential advantages over 3-T MRI, particularly in cartilage assessment. However, superiority was not shown for all parameters; for example, visualization of the triangular fibrocartilage complex and wrist ligaments was superior at 3 T. © RSNA, 2023 Supplemental material is available for this article.

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

OBJECTIVES: We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms. METHODS: The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM-KOA worsening association is mediated through preceding muscle degeneration. RESULTS: After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI -0.16%/year, -0.25 to -0.07, and -0.21%/year, -0.33 to -0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18-2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM. CONCLUSIONS: Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA. KEY POINTS: • Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms. • As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

Clinical, patient-reported, radiographic and magnetic resonance imaging findings 11 years after acute posterior cruciate ligament injury treated non-surgically.

BACKGROUND: Long-term consequences of posterior cruciate ligament (PCL) injury such as persistent posterior tibial translation and risk of osteoarthritis development are unclear. Additionally, little data is available describing the natural history of structural morphology of the ruptured PCL. The purpose of the study was to determine the long-term outcome after non-operatively treated PCL injury. METHODS: Over 6-years, all acute knee injuries were documented by subacute MRI (median 8 days [5-15, 25th - 75th percentile] from injury to MRI). Twenty-six patients with acute PCL injury were identified of whom 18 (69%) participated in the long-term follow-up after 11 years. Follow-up included radiographic posterior tibial translation (RPTT) determined using the Puddu axial radiograph. weight-bearing knee radiographs, MRI and KOOS (Knee injury and Osteoarthritis Outcome Score). RESULTS: On subacute MRI, 11 knees displayed total and 7 partial ruptures. At 11 (SD 1.9) years, the median RPTT was 3.7 mm (1.5-6.3, 25th - 75th percentile). Seven knees displayed radiographic osteoarthritis approximating Kellgren-Lawrence grade ≥ 2. All follow-up MRIs displayed continuity of the PCL. Patients with more severe RPTT (> 3.7 mm), had worse scores in the KOOS subscales for symptoms (mean difference 14.5, 95% CI 7-22), sport/recreation (30, 95% CI 0-65) and quality of life (25, 95% CI 13-57) than those with less severe RPTT (≤ 3.7 mm). This was also the case for the KOOS4 (22, 95% CI 9-34). CONCLUSION: Acute PCL injuries treated non-surgically display a high degree of PCL continuity on MR images 11 years after injury. However, there is a large variation of posterior tibial translation with higher values being associated with poorer patient-reported outcomes.

Joint interventions in osteoarthritis.

Osteoarthritis (OA) is among the most common diseases affecting both axial and appendicular joints and the lead cause of disability worldwide. OA incidence is rising due to extended life expectancy and the increasing obesity epidemic. Several joint interventions are available to manage pain and joint function in patients with OA, most of these treatments being widely applied using intra-articular injections. In this chapter, we will describe the different joint interventions available for the management of pain in OA focusing on intra-articular injections, including discussion on the evidence regarding the efficacy of these treatments, based on the most recent systematic reviews and meta-analyses available. We also discuss the importance of imaging in guiding these treatments, including the different imaging modalities available for intra-articular injection guidance, their advantages, and disadvantages. Finally, we briefly discuss safety data and the consensus regarding the most used intra-articular treatments to manage pain in OA.

Update on recent developments in imaging of inflammation in osteoarthritis: a narrative review.

Synovitis is an important component of the osteoarthritis (OA) disease process, particularly regarding the "inflammatory phenotype" of OA. Imaging plays an important role in the assessment of synovitis in OA with MRI and ultrasound being the most deployed imaging modalities. Contrast-enhanced (CE) MRI, particularly dynamic CEMRI (DCEMRI) is the ideal method for synovitis assessment, but for several reasons CEMRI is not commonly performed for OA imaging in general. Effusion-synovitis and Hoffa-synovitis are commonly used as surrogate markers of synovitis on non-contrast-enhanced (NCE) MRI and have been used in many epidemiological observational studies of knee OA. Several semiquantitative MRI scoring systems are available for the evaluation of synovitis in knee OA. Synovitis can be a target tissue for disease-modifying OA drug (DMOAD) clinical trials. Both MRI and ultrasound may be used to determine the eligibility and assess the therapeutic efficacy of DMOAD approaches. Ultrasound is mostly used for evaluation of synovitis in hand OA, while MRI is typically used for larger joints, namely knees and hips. The role of other modalities such as CT (including dual-energy CT) and nuclear medicine imaging (such as positron-emission tomography (PET) and its hybrid imaging) is limited in the context of synovitis assessment in OA. Despite research efforts to develop NCEMRI-based synovitis evaluation methods, these typically underestimate the severity of synovitis compared to CEMRI, and thus more research is needed before we can rely only on NCEMRI.

A call for screening MRI as a tool for osteoarthritis clinical trials.

Conventional radiography is the most commonly used imaging modality for the evaluation of osteoarthritis (OA) in clinical trials of disease-modifying OA drugs (DMOADs). Unfortunately, radiography has many shortcomings as an imaging technique to meaningfully assess the pathological features of OA. In this perspective paper, we will describe the reasons why radiography is not an ideal tool for structural OA assessment and why magnetic resonance imaging (MRI) should be preferred for such purposes. These shortcomings include a lack of reproducibility of radiographic joint space measurements (if conducted without using a standardized positioning frame), a lack of sensitivity and specificity, an insufficient definition of disease severity, a weak association of radiographic structural damage and pain, a lack of ability to depict many faces of OA, and incapability to depict diagnoses of exclusion. MRI offers solutions to these limitations of radiography. Several different phenotypes of OA have been recognized and it is important to recruit appropriate patients for specific therapeutic approaches in DMOAD trials. Radiography does not allow such phenotypical stratification. We will explain known hurdles for widespread deployment of MRI at eligibility screening and how they can be overcome by technological advances and the use of simplified image assessment.

Structural phenotypes of knee osteoarthritis: potential clinical and research relevance.

A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in the presence of concomitant cartilage damage. Limitations of the concept of structural phenotyping are that they are not mutually exclusive and that more than one phenotype may be present. It must be acknowledged that a wide range of views exist on how best to operationalize the concept of structural OA phenotypes and that the concept of structural phenotypic characterization is still in its infancy. Structural phenotypic stratification, however, may result in more targeted trial populations with successful outcomes and practitioners need to be aware of the heterogeneity of the disease to personalize their treatment recommendations for an individual patient. Radiologists should be able to define a joint at risk for progression based on the predominant phenotype present at different disease stages.