Datasets for the reporting of primary tumour in bone: recommendations from the International Collaboration on Cancer Reporting (ICCR).

BACKGROUND AND OBJECTIVES: Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. METHODS AND RESULTS: According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and a radiologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were bone tumour experts affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the datasets, including a synoptic reporting guide, were published on the ICCR website. CONCLUSION: These first international datasets for bone sarcomas are intended to promote high-quality, standardised pathology reporting. Their widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve management of bone sarcoma patients.

Comparison between 1.5T and 3.0T MRI: both field strengths sensitively detect subclinical inflammation of hand and forefoot in patients with arthralgia.

OBJECTIVE: Magnetic resonance imaging (MRI) of small joints sensitively detects inflammation. This inflammation, and tenosynovitis in particular, has been shown to predict rheumatoid arthritis (RA) development in arthralgia patients. These data have predominantly been acquired on 1.0-1.5 T MRI. However, 3.0 T is now commonly used in practice. Evidence on the comparability of these field strengths is scarce and has never included subtle inflammation in arthralgia patients or tenosynovitis. Therefore, we assessed the comparability of 1.5 T and 3.0 T in detecting subclinical inflammation in arthralgia patients. METHOD: A total of 2968 locations (joints, bones, tendon sheaths) in the hands and forefeet of 28 patients with small-joint arthralgia, at risk for RA, were imaged on both 1.5 and 3.0 T MRI. Two blinded readers independently scored erosions, osteitis, synovitis, and tenosynovitis, in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS). Features were summed into inflammation (osteitis, synovitis, tenosynovitis) and RAMRIS (inflammation and erosions). Agreement was assessed with intraclass correlation coefficients (ICCs) for continuous scores and after dichotomization into presence or absence of inflammation, on patient and location levels. RESULTS: Interreader ICCs were excellent (> 0.90). Comparing 1.5 and 3.0 T revealed an ICC of 0.90 for inflammation and RAMRIS. ICCs for individual inflammation features were: tenosynovitis 0.87 (95% confidence interval 0.74-0.94), synovitis 0.65 (0.24-0.84), and osteitis 0.96 (0.91-0.98). Agreement was 83% for inflammation and 89% for RAMRIS. Analyses on the location level showed similar results. CONCLUSION: Agreement on subclinical inflammation between 1.5 T and 3.0 T was excellent. Although synovitis scores were slightly different, synovitis often occurs simultaneously with other inflammatory signs, suggesting that scientific results on the predictive value of MRI-detected inflammation for RA, obtained on 1.5 T MRI, can be generalized to 3.0 T MRI.

Personalising sarcoma care using quantitative multimodality imaging for response assessment.

Over the last decades, technological developments in the field of radiology have resulted in a widespread use of imaging for personalising medicine in oncology, including patients with a sarcoma. New scanner hardware, imaging protocols, image reconstruction algorithms, radiotracers, and contrast media, enabled the assessment of the physical and biological properties of tumours associated with response to treatment. In this context, medical imaging has the potential to select sarcoma patients who do not benefit from (neo-)adjuvant treatment and facilitate treatment adaptation. Due to the biological heterogeneity in sarcomas, the challenge at hand is to acquire a practicable set of imaging features for specific sarcoma subtypes, allowing response assessment. This review provides a comprehensive overview of available clinical data on imaging-based response monitoring in sarcoma patients and future research directions. Eventually, it is expected that imaging-based response monitoring will help to achieve successful modification of (neo)adjuvant treatments and improve clinical care for these patients.

Effusion attenuates the effect of synovitis on radiographic progression in patients with hand osteoarthritis: a longitudinal magnetic resonance imaging study.

An exploratory study to determine the role of effusion, i.e., fluid in the joint, in pain, and radiographic progression in patients with hand osteoarthritis. Distal and proximal interphalangeal joints (87 patients, 82% women, mean age 59 years) were assessed for pain. T2-weighted and Gd-chelate contrast-enhanced T1-weighted magnetic resonance images were scored for enhanced synovial thickening (EST, i.e., synovitis), effusion (EST and T2-high signal intensity [hsi]) and bone marrow lesions (BMLs). Effusion was defined as follows: (1) T2-hsi > 0 and EST = 0; or 2) T2-hsi = EST but in different joint locations. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence, increase ≥ 1 defined progression. Associations between the presence of effusion and pain and radiographic progression, taking into account EST and BML presence, were explored on the joint level. Effusion was present in 17% (120/691) of joints, with (63/120) and without (57/120) EST. Effusion on itself was not associated with pain or progression. The association with pain and progression, taking in account other known risk factors, was stronger in the absence of effusion (OR [95% CI] 1.7 [1.0-2.9] and 3.2 [1.7-5.8]) than in its presence (1.6 [0.8-3.0] and 1.3 [0.5-3.1]). Effusion can be assessed on MR images and seems not to be associated with pain or radiographic progression but attenuates the association between synovitis and progression. Key Points • Effusion is present apart from synovitis in interphalangeal joints in patients with hand OA. • Effusion in finger joints can be assessed as a separate feature on MR images. • Effusion seems to be of importance for its attenuating effect on the association between synovitis and radiographic progression.

18F-FDG PET-CT versus MRI for detection of skeletal metastasis in Ewing sarcoma.

OBJECTIVE: To determine the level of discrepancy between magnetic resonance imaging (MRI) and 18F-FDG PET-CT in detecting osseous metastases in patients with Ewing sarcoma. METHODS: Twenty patients with histopathologically confirmed Ewing sarcoma between 2000 and 2017 who underwent 18F-FDG PET-CT and MRI within a 4-week range were included. Each imaging modality was evaluated by a separate observer. Reference diagnosis of each lesion was based on histopathology or consensus of an expert panel using all available data, including at least 6 months' follow-up. Sensitivity, specificity, and predictive values were determined. Osseous lesions were analyzed on a patient and a lesion basis. Factors possibly related to false-negative findings were evaluated using Pearson's Chi-squared or Fisher's exact test. RESULTS: A total of 112 osseous lesions were diagnosed in 13 patients, 107 malignant and 5 benign. Seven patients showed no metastases on either 18F-FDG PET-CT or MRI. Forty-one skeletal metastases (39%) detected with MRI did not show increased 18F-FDG uptake on 18F-FDG PET-CT (false-negative). Lesion-based sensitivities and specificities were 62% (95%CI 52-71%) and 100% (48-100%) for 18F-FDG PET-CT; and 99% (97-100%) and 100% (48-100%) for MRI respectively. Bone lesions were more likely to be false-negative on 18F-FDG PET-CT if hematopoietic bone marrow extension was widespread and active (p = 0.001), during or after (neo)-adjuvant treatment (p = 0.001) or when the lesion was smaller than 10 mm (p < 0.001). CONCLUSION: Although no definite conclusions can be drawn from this small retrospective study, it shows that caution is needed when using 18F-FDG PET-CT for diagnosing skeletal metastases in Ewing sarcoma. Poor contrast between metastases and active hematopoietic bone marrow, chemotherapeutic treatment, and/or small size significantly decrease the diagnostic yield of 18F-FDG PET-CT, but not of MRI.

Assessment of osteoarthritic features in the thumb base with the newly developed OMERACT magnetic resonance imaging scoring system is a valid addition to standard radiography.

OBJECTIVE: To investigate the construct validity of the new thumb base OA magnetic resonance imaging (MRI) scoring system (TOMS) by comparing TOMS scores with radiographic scores in patients with primary hand OA. DESIGN: In 200 patients (83.5% women, mean (SD) age 61.0 (8.4) years), postero-anterior radiographs and MR scans (1.5 T) of the right first carpometacarpal (CMC-1) and scaphotrapeziotrapezoid (STT) joints, were scored using the OARSI atlas and TOMS, respectively. The distributions of the TOMS scores (specified in results section) were stratified for the OARSI scores of corresponding radiographic features and investigated using boxplots and non-parametric tests. Furthermore, Spearman's rank or Phi correlation coefficients (ρ/φ) were calculated. RESULTS: For all features, especially for erosions and osteophytes, the prevalence found with MRI was higher than with radiography. TOMS osteophyte and cartilage loss scores differed statistically significant between corresponding OARSI scores in CMC-1 (0 vs 1; 1 vs 2). TOMS scores were positively correlated with radiographic scores in CMC-1 for osteophytes (coefficient [95% confidence interval], ρ = 0.75 [0.69; 0.81]), cartilage loss/joint space narrowing (ρ = 0.70 [0.62; 0.76]), subchondral bone defects (SBDs)/erosion-cyst (ρ = 0.41 [0.29; 0.52]), bone marrow lesions (BMLs)/subchondral sclerosis (ρ = 0.65 [0.56; 0.73]) and subluxation (φ = 0.65 [0.57; 0.73]); and in STT for osteophytes (ρ = 0.30 [0.17; 0.42]) and cartilage loss/joint space narrowing (ρ = 0.53 [0.42; 0.62]). CONCLUSIONS: In patients with hand OA, TOMS scores positively correlated with radiographic scores, indicating good construct validity. However, the prevalence of features on MR images was higher compared to radiographs, suggesting that TOMS might be more sensitive than radiography. The clinical meaning of these extra MR detected cases is currently still unknown.

Severity classification of Tenosynovial Giant Cell Tumours on MR imaging.

AIM: Current development of novel systemic agents requires identification and monitoring of extensive Tenosynovial Giant Cell Tumours (TGCT). This study defines TGCT extension on MR imaging to classify severity. METHODS: In part one, six MR parameters were defined by field-experts to assess disease extension on MR images: type of TGCT, articular involvement, cartilage-covered bone invasion, and involvement of muscular/tendinous tissue, ligaments or neurovascular structures. Inter- and intra-rater agreement were calculated using 118 TGCT MR scans. In part two, the previously defined MR parameters were evaluated in 174 consecutive, not previously used, MR-scans. TGCT severity classification was established based on highest to lowest Hazard Ratios (HR) on first recurrence. RESULTS: In part one, all MR parameters showed good inter- and intra-rater agreement (Kappa≥0.66). In part two, cartilage-covered bone invasion and neurovascular involvement were rarely appreciated (<13%) and therefore excluded for additional analyses. Univariate analyses for recurrent disease yielded positive associations for type of TGCT HR12.84(95%CI4.60-35.81), articular involvement HR6.00(95%CI2.14-16.80), muscular/tendinous tissue involvement HR3.50(95%CI1.75-7.01) and ligament-involvement HR4.59(95%CI2.23-9.46). With these, a TGCT severity classification was constructed with four distinct severity-stages. Recurrence free survival at 4 years (log rank p < 0.0001) was 94% in mild localized (n56, 1 recurrence), 88% in severe localized (n31, 3 recurrences), 59% in moderate diffuse (n32, 12 recurrences) and 36% in severe diffuse (n55, 33 recurrences). CONCLUSION: The proposed TGCT severity classification informs physicians and patients on disease extent and risk for recurrence after surgical treatment. Definition of the most severe subgroup attributes to a universal identification of eligible patients for systemic therapy or trials for novel agents.

Comparison of histological and morphometrical changes underlying subchondral bone abnormalities in inflammatory and degenerative musculoskeletal disorders: a systematic review.

OBJECTIVE: Subchondral bone abnormalities (SBAs) on magnetic resonance imaging (MRI) are observed frequently and associated with disease course in various musculoskeletal disorders. This review aims to map the existing knowledge of their underlying histological features, and to identify needs for future research. DESIGN: We conducted a systematic review following PRISMA guidelines until September 2017, including all studies correlating histological features to on MRI defined SBAs in patients with osteoarthritis (OA), rheumatoid arthritis (RA), spondyloarthritis (SpA) and degenerative disc disease (DDD). Two authors independently retrieved articles and assessed study quality. RESULTS: A total of 21 studies (466 patients) correlated histological features to SBAs in OA (n = 13), RA (n = 3), ankylosing spondylitis (AS) (n = 1) and DDD (n = 4). Reported changes in OA were substitution of normal subchondral bone with fibrosis and necrosis, and increased bone remodeling. In contrast, in RA, AS or DDD fibrosis was not reported and SBAs correlated to an increase in inflammatory cell number. In DDD necrosis was observed. Similar to OA, increased bone remodeling was shown in RA and DDD. The risk of bias assessment showed a lack in described patient criteria, blinding and/or adequate topographic correlation in approximately half of studies. There was heterogeneity regarding the investigated histological features between the different disorders. CONCLUSIONS: Current studies suggest that SBAs correlate to various histological features, including fibrosis, cell death, inflammation and bone remodeling. In the majority of studies most quality criteria were not met. Future studies should aim for high quality research, and consistency in investigated features between different disorders.

In thumb base osteoarthritis structural damage is more strongly associated with pain than synovitis.

OBJECTIVE: Osteoarthritis in thumb base joints (first carpometacarpal (CMC-1), scaphotrapeziotrapezoid (STT)) is prevalent and disabling, yet focussed studies are scarce. Our aim was to investigate associations between ultrasonographic and magnetic resonance imaging (MRI) inflammatory features, radiographic osteophytes, and thumb base pain in hand osteoarthritis patients. DESIGN: Cross-sectional analyses were performed in cohorts with MRI (n = 202) and ultrasound measurements (n = 87). Pain upon thumb base palpation was assessed. Radiographs were scored for CMC-1/STT osteophytes. Synovial thickening, effusion and power Doppler signal in CMC-1 joints were assessed with ultrasound. MRIs were scored for synovitis and bone marrow lesions (BMLs) in CMC-1 and STT joints using OMERACT-TOMS. Associations between ultrasound/MRI features, osteophytes, and thumb base pain were assessed. Interaction between MRI features and osteophytes was explored. RESULTS: In 289 patients (mean age 60.2, 83% women) 139/376 thumb bases were painful. Osteophyte presence was associated with pain (MRI cohort: odds ratio (OR) 5.1 (2.7-9.8)). Ultrasound features were present in 25-33% of CMC-1 joints, though no associations were seen with pain. MRI-synovitis and BMLs grade ≥2 were scored in 25% and 43% of thumb bases, and positively associated with pain (OR 3.6 (95% CI 1.7-7.6) and 3.0 (1.6-5.5)). Associations attenuated after adjustment for osteophyte presence. Combined presence of osteophytes and MRI-synovitis had an additive effect. CONCLUSIONS: Ultrasonographic and MRI inflammatory features were often present in the thumb base. Osteophytes were more strongly associated with thumb base pain than inflammatory features, in contrast to findings in finger OA studies, supporting thumb base osteoarthritis as a distinct phenotype.

Bone marrow lesions on magnetic resonance imaging in hand osteoarthritis are associated with pain and interact with synovitis.

OBJECTIVE: To determine the association between bone marrow lesions (BMLs) and (teno)synovitis as assessed on magnetic resonance (MR) imaging in patients with pain in hand osteoarthritis (OA). METHODS: In 105 consecutive primary hand OA patients (83% women, mean age 59 years), who were diagnosed by rheumatologists and included in the HOSTAS (Hand OSTeoArthritis in Secondary care) cohort, contrast enhanced MR imaging of right distal and proximal interphalangeal joints were obtained. In 92 patients joint site specific pain upon palpation was assessed within 3 weeks of magnetic resonance imaging (MRI) examination. MR features were scored (0-3) following the Oslo hand OA score: BMLs, synovitis, cysts, flexor tenosynovitis (FTS). Additionally, extensor tendon inflammation (ETI) (0-3) was scored. Odds ratios (OR, 95% confidence interval (CI)) were calculated using generalized estimating equations for MR features with joint pain, adjusted for putative confounders. Stratified analyses were performed to investigate interaction. RESULTS: BMLs, synovitis, cysts, FTS and ETI were demonstrated in 56%, 90%, 22%, 16% and 30% of patients, respectively. BMLs (grade 2/3 vs 0: 3.5 (1.6-7.7)) and synovitis (3 vs 0: OR 3.6 (95% CI 1.9-6.6)) were severity-dependent associated with joint pain, but FTS and ETI were not. Stratified analyses showed that BMLs did not associate with pain in the absence of synovitis, whereas synovitis was associated with pain in the absence of BMLs. Interaction was seen between BMLs and synovitis grade 2 or 3. CONCLUSION: In hand OA patients severe synovitis is associated with joint pain, which is worsened when BMLs co-occur, suggesting synovitis as primary target of treatment.

Prevalence and clinical significance of lumbosacral transitional vertebra (LSTV) in a young back pain population with suspected axial spondyloarthritis: results of the SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVE: To determine in a cohort of young patients with suspected axial spondyloarthritis (axSpA), the prevalence of lumbosacral transitional vertebra (LSTV), its association with local bone marrow edema (BME) and lumbar spine degeneration, and the potential relationship with MRI findings and clinical signs of axSpA. MATERIALS AND METHODS: Baseline imaging studies and clinical information of patients from the SPondyloArthritis Caught Early-cohort (back pain ≥3 months, ≤2 years, onset <45 years) were used. Two independent readers assessed all patients for LSTV on radiography, and BME-like and degenerative changes on MRI. Patients with and without LSTV were compared with regard to the prevalence of MRI findings and the results of clinical assessment using Chi-squared test or t test. RESULTS: Of 273 patients (35.1% male, mean age 30.0), 68 (25%) patients showed an LSTV, without statistical significant difference between patients with and without axSpA (p = 0.327). Local sacral BME was present in 9 out of 68 (13%) patients with LSTV and absent in patients without LSTV (p < 0.001). Visual analogue scale (VAS) pain score and spinal mobility assessments were comparable. CONCLUSIONS: LSTV is of low clinical relevance in the early diagnosis of axSpA. There is no difference between patients with and without LSTV regarding the prevalence of axSpA, pain and spinal mobility, and a BME-like pattern at the pseudoarticulation does not reach the SI joints.

Bone marrow lesions and synovitis on MRI associate with radiographic progression after 2†years in hand osteoarthritis.

OBJECTIVE: To study the association of magnetic resonance (MR) features with radiographic progression of hand osteoarthritis over 2 years. METHODS: Of 87 primary patients with hand osteoarthritis (82% women, mean age 59 years), baseline distal and proximal interphalangeal joint contrast-enhanced MR images were scored 0-3 for bone marrow lesions (BMLs) and synovitis following the Oslo score. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence (KL) (0-4) and OsteoArthritis Research Society International (OARSI) scoring methods (0-3 osteophytes, joint space narrowing (JSN)). Increase ≥1 defined progression. Associations between MR features and radiographic progression were explored on joint and on patient level, adjusting for age, sex, body mass index, synovitis and BML. Joints in end-stage were excluded. RESULTS: Of 696 analysed joints, 324 had baseline KL=0, 28 KL=4 and after 2 years 78 joints progressed. BML grade 2/3 was associated with KL progression (2/3 vs 0: adjusted risk ratio (RR) (95% CI) 3.3 (2.1 to 5.3)) and with osteophyte or JSN progression, as was synovitis. Summated scores were associated with radiographic progression on patient level (RR crude BML 1.08 (1.01 to 1.2), synovitis 1.09 (1.04 to 1.1), adjusted synovitis 1.08 (1.03 to 1.1)). CONCLUSIONS: BMLs, next to synovitis, show, already after 2 years, graded associations with radiographic progression, suggesting that both joint tissues could be important targets for therapy.

Bakers' cyst and tibiofemoral abnormalities are more distinctive MRI features of symptomatic osteoarthritis than patellofemoral abnormalities.

OBJECTIVE: To investigate which structural MR abnormalities discriminate symptomatic knee osteoarthritis (OA), taking co-occurrence of abnormalities in all compartments into account. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45-65 years. In 1285 participants (median age 56 years, 55% women, median body mass index (BMI) 30 kg/m(2)), MRI of the right knee were obtained. Structural abnormalities (osteophytes, cartilage loss, bone marrow lesions (BMLs), subchondral cysts, meniscal abnormalities, effusion, Baker's cyst) at 9 patellofemoral and tibiofemoral locations were scored following the knee OA scoring system. Symptomatic OA in the imaged knee was defined following the American College of Rheumatology criteria. Logistic ridge regression analyses were used to investigate which structural abnormalities discriminate best between individuals with and without symptomatic OA, crude and adjusted for age, sex and BMI. RESULTS: Symptomatic knee OA was present in 177 individuals. Structural MR abnormalities were highly frequent both in individuals with OA and in those without. Baker's cysts showed the highest adjusted regression coefficient (0.293) for presence of symptomatic OA, followed by osteophytes and BMLs in the medial tibiofemoral compartment (0.185-0.279), osteophytes in the medial trochlear facet (0.262) and effusion (0.197). CONCLUSIONS: Baker's cysts discriminate best between individuals with and without symptomatic knee OA. Structural MR abnormalities, especially in the medial side of the tibiofemoral joint and effusion, add further in discriminating symptomatic OA. Baker's cysts may present as a target for treatment.

Evolution of synovitis in osteoarthritic knees and its association with clinical features.

OBJECTIVE: To investigate the course of synovitis on contrast-enhanced magnetic resonance images (CE-MRI) in osteoarthritic knees over 2 years, and its association with pain and cartilage deterioration. DESIGN: Consecutive patients (n = 39, mean age 61 years, 79% woman, median (range) body mass index (BMI) 29 (24-48) kg/mm2) with clinical osteoarthritis (OA) were included. Baseline and follow-up CE-MRI (3 T) were scored paired in chronological order for synovitis (semi-quantitatively at 11 sites (range 0-22)), cartilage deterioration and bone marrow lesions (BMLs) (semi-quantitatively according to Knee Osteoarthritis Scoring System (KOSS)). Changes in sum scores were calculated. Cartilage deterioration was defined as change of ≥2 above the smallest detectable change (SDC). Pain was assessed by standardized questionnaires. Analysis of covariance (ANCOVA) and linear regression models were used to investigate association between synovitis change and cartilage deterioration and between synovitis change or cartilage deterioration and change in pain. RESULTS: The total synovitis score did not change over 2 years (mean change 0.2 (standard deviation (SD) 3.2)), although changes in individual patients were observed. Cartilage deterioration was observed in 51% of patients. Synovitis change score was lower in patients without compared to patients with cartilage deterioration, taking BML change in account (mean difference -2.1 (-4.1 to -0.1)). Change in synovitis was not associated with change in pain, whereas cartilage deterioration was associated with change in Intermittent and Constant OsteoArthritis Pain (ICOAP) constant pain in adjusted models (unstandardised coefficient (B) (95% confidence interval (CI)) 2.8 (0.4-5.3)). CONCLUSIONS: In individual patients synovitis fluctuates during disease course. Synovitis change was not associated with change in pain. Increase in synovitis is associated with cartilage deterioration, suggesting a role for synovitis as a target for disease-modifying treatment.

Evaluation of response after pre-operative radiotherapy in soft tissue sarcomas; the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group recommendations for radiological examination and reporting with an emphasis on magnetic resonance imaging.

At present, there is no standardised approach for the radiological evaluation of soft tissue sarcomas following radiotherapy (RT). This manuscript, produced by a European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group endorsed task force, aims to propose standardisation of magnetic resonance imaging techniques and interpretation after neoadjuvant RT for routine use and within clinical trials.

Radiographic progression of knee osteoarthritis is associated with MRI abnormalities in both the patellofemoral and tibiofemoral joint.

OBJECTIVE: To investigate patterns of MRI abnormalities in the patellofemoral (PFJ) and tibiofemoral joint (TFJ) and their association with radiographic progression, using hypothesis free analyses. DESIGN: 205 patients from the GARP study with symptomatic OA at multiple sites (mean age 60 years, 80% woman, median BMI 26 kg/m(2)), underwent knee MRI at baseline. Cartilage damage, osteophytes, cysts, bone marrow lesions (BMLs) and effusion/synovitis were scored according to a validated scoring method. Baseline and 6-year TFJ and PFJ radiographs were scored (0-3) for JSN and osteophytes according to OARSI and Burnett atlases, respectively; progression was defined as ≥1 point increase. Baseline patterns of MRI abnormalities derived from principal component analysis (PCA) were associated with progression using adjusted generalized estimating equations (GEE). RESULTS: PCA resulted in extraction of six components, explaining 69% of variance. In 29% and 29% of 133 patients with follow-up the TFJ progressed, whereas in 15% and 9% the PFJ progressed for osteophytes and JSN, respectively. Component 1 (cartilage damage of the PFJ and osteophytes of both joints) was statistically significant associated with TFJ JSN progression and PFJ osteophyte progression. Component 2 (all lateral PFJ abnormalities except osteophytes) was associated with JSN/osteophyte progression in the PFJ alone, whereas component 3 (all medial TFJ abnormalities except osteophytes) was associated with JSN and osteophyte progression in both PFJ and TFJ. CONCLUSION: Baseline structural damage and bone turnover activity, as reflected by BMLs, seem to be involved in knee OA progression. Moreover, progression in PFJ and TFJ seems to be related.

Signal intensity loss of the intervertebral discs in the cervical spine of young patients on fluid sensitive sequences.

OBJECTIVE: To evaluate the signal intensity (SI) of the intervertebral discs of the cervical spine on magnetic resonance (MR) fluid sensitive sequences, and correlate this to secondary signs of degeneration on MR and radiographs as well as to age. MATERIAL AND METHODS: A total of 265 patients aged ≥16 with back pain (≥3-months, <2-year, onset <45-years) from the SPondyloArthritis Caught Early (SPACE) cohort were included. Sagittal 1.5 T MR images and lateral radiographs of the cervical spine were independently evaluated by two readers for: SI of the intervertebral discs using a grading system based of Pfirrmann (grade 1 normal/bright SI; 2 inhomogeneous/bright SI; 3 inhomogeneous/mildly decreased SI; 4 inhomogeneous/markedly decreased SI; 5 signal void), disc herniation and Modic changes (MRI) and disc space narrowing, osteophytes and sclerosis (radiograph). Readers were blinded for clinical information. Descriptive statistics were used for characteristics and prevalence of findings, and regression analysis was used for age and grades. RESULTS: Of 265 patients (36% male, mean age 30), 221 (83%) patients had 1 to 6 discs (median 4) with decreased SI. Of 1,590 discs, 737 (46%) were grade 1; 711 (45%) grade 2; 133 (8%) grade 3; 8 (1%) grade 4 and 1 (0%) grade 5. Secondary signs of degeneration were rare and seen predominantly in C5-C7 and appear to be related to signal loss grade 3 and 4. CONCLUSION: Low signal intensity of intervertebral discs in absence of secondary degenerative signs in the cervical spine on fluid sensitive MR images might be pre-existing and part of the natural course.

Characterization of synovial mast cells in knee osteoarthritis: association with clinical parameters.

OBJECTIVE: To investigate the presence of mast cells in the osteoarthritic (OA) synovium and their association with clinical parameters in comparison with rheumatoid arthritis (RA) samples. METHOD: Synovial tissues of 56 symptomatic OA and 49 RA patients were obtained. Two to three paraffin slides were used to quantify inflammation using haematoxylin and eosin (H&E) staining (synovitis score 0-9), and numbers of mast cells (per 10 high-power fields) using double immunofluorescence for CD117 and tryptase. Average scores per patient were used for analysis. Knee radiographs of OA patients were scored according to the Kellgren and Lawrence (KL) system and pain was determined in OA patients at baseline by visual analogue scale (VAS). RESULTS: Median (range) of mast cells was significantly higher in OA samples 45 (1-168) compared to RA samples 4 (1-47) (P-value < 0.001), despite a lower median (range) synovitis score in OA (2.5 (0-6.0)) compared to 4.6 (0-8.0) in RA samples. The synovitis score was significantly correlated with the number of mast cells (in OA Spearman's rho (P-value) 0.3 (0.023) and RA 0.5 (P-value < 0.001)). Interestingly, we observed a trend towards an association between the number of mast cells and an increased KL-grade (P-value 0.05) in OA patients, independently of synovitis. No associations were found with self-reported pain. CONCLUSION: Prevalence of mast cells in OA synovial tissue is relatively high and associates with structural damage in OA patients, suggesting a role of mast cells in this disease.

Association of pain in knee osteoarthritis with distinct patterns of synovitis.

OBJECTIVE: To determine possible patterns of synovitis on contrast-enhanced magnetic resonance imaging (CE-MRI) and its relation to pain and severity in patients with radiographic knee osteoarthritis (OA). METHODS: In total, 86 patients (mean age 62 years, 66% women, median body mass index 29 kg/m(2) ) with symptomatic knee OA (Kellgren/Lawrence radiographic score 3) were included. T1-weighted, gadolinium-chelate-enhanced MRI with fat suppression was used to semiquantitatively score the extent of synovitis at 11 knee sites (total score range 0-22). Self-reported pain was assessed with 3 standardized questionnaires. Principal components analysis (PCA) was used to investigate patterns (the location and severity) of synovitis. Subsequently, these patterns were assessed for associations with pain measures and radiographic severity in adjusted logistic regression models. RESULTS: Synovitis was observed in 86 patients and was found to be generally mild on CE-MRI (median total synovitis score 7, range 0-16). The median pain scores were 53 (range 0-96) on the visual analog scale for pain, 51.4 (range 2.8-97.2) on the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, 35 (range 0-75) on the Intermittent and Constant Osteoarthritis Pain (ICOAP) score for constant pain, and 40.6 (range 0-87.5) on the ICOAP score for intermittent pain. PCA resulted in extraction of 3 components, explaining 53.4% of the variance. Component 1 was characterized by synovitis at 7 sites (mainly medial parapatellar involvement) and was associated with scores on the KOOS pain subscale and the ICOAP constant pain subscale. Component 2 was characterized by synovitis at 4 sites (mainly the site adjacent to the anterior cruciate ligament), but was not associated with pain measures or with radiographic severity. Component 3, characterized by synovitis at 3 sites (mainly at the loose body site), was associated with radiographic severity. CONCLUSION: Different patterns of synovitis in knee OA were observed. The pattern that included several patellar sites was associated with pain, whereas other patterns showed no association, suggesting that pain perception in patients with knee OA is a localized response.

Concordance between inflammation at physical examination and on MRI in patients with early arthritis.

BACKGROUND: MRI is increasingly used to measure inflammation in rheumatoid arthritis (RA) research, but the correlation to clinical assessment is unexplored. This study determined the association and concordance between inflammation of small joints measured with MRI and physical examination. METHODS: 179 patients with early arthritis underwent a 68 tender joint count and 66 swollen joint count and 1.5T MRI of MCP (2-5), wrist and MTP (1-5) joints at the most painful side. Two readers scored synovitis and bone marrow oedema (BME) according to the OMERACT RA MRI scoring method and assessed tenosynovitis. The MRI data were first analysed continuously and then dichotomised to analyse the concordance with inflammation at joint examination. RESULTS: 1790 joints of 179 patients were studied. Synovitis and tenosynovitis on MRI were independently associated with clinical swelling, in contrast to BME. In 86% of the swollen MCP joints and in 92% of the swollen wrist joints any inflammation on MRI was present. In 27% of the non-swollen MCP joints and in 66% of the non-swollen wrist joints any MRI inflammation was present. Vice versa, of all MCP, wrist and MTP joints with inflammation on MRI 64%, 61% and 77%, respectively, were not swollen. BME, also in case of severe lesions, occurred frequently in clinically non-swollen joints. Similar results were observed for joint tenderness. CONCLUSIONS: Inflammation on MRI is not only present in clinically swollen but also in non-swollen joints. In particular BME occurred in clinically non-inflamed joints. The relevance of subclinical inflammation for the disease course is a subject for further studies.