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The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method for detecting and quantifying joint damage in RA. However, radiographs only show late disease manifestations as joint space narrowing and bone erosions, whereas it cannot detect synovitis and bone marrow oedema, i.e., inflammation in the synovium or the bone, which may be visualized by magnetic resonance imaging (MRI) months to years before erosions develop. Furthermore, MRI allows earlier visualization of bone erosions than radiography. In order to allow early treatment initiation and optimal guidance of the therapeutic strategy, there is a need for methods which are capable of early detection of inflammatory joint changes. In this review, we will discuss available data, advantages, limitations and potential future of MRI in RA.

Objective: To investigate the distribution of an ultrasound-guided intra-articular (IA) injection in the wrist joint of patients with rheumatoid arthritis (RA)., Methods: An ultrasound-guided IA drug injection into the wrist joint was performed in 17 patients with 1 ml methylprednisolone (40 mg/ml), 0.5 ml Lidocaine (5mg/ml) and 0.15 ml gadolinium (Omniscan 0.5 mmol/ml). The drug solution was placed in the central proximal part of the wrist between the distal radius and the lunate bone. Coronal and axial MRI sequences were performed after the injection to visualize the distribution. Carpal distribution (radio-carpal, inter-carpal, and carpo-metacarpal) as well as radio-ulnar distribution was recorded. Full distribution in one compartment was given the value 1, partial distribution 0.5 and no distribution 0. A sum of the total distribution for all four compartments was calculated and correlated to the clinical parameters and the MRI OMERACT scores., Results: No uniform pattern was seen in the distribution of the contrast. Only two patients had full contrast distribution to all four compartments, and the mean distribution count for all patients was 2.4 (range 0.5-4). The distribution count correlated with the MRI OMERACT synovitis score (r=0.60, p=0.014), but not with the erosions, bonemarrow oedema scores or any clinical parameters., Conclusion: The distribution of contrast on MRI showed patient specific and random patterns after IA injections in active RA wrist joints. The degree of distribution increased with the MRI synovitis score, while no association was found with the erosion- and bonemarrow oedema score. These results indicate that a single injection into a standard injection site in the proximal part of the wrist cannot be assumed to distribute--and treat--the whole joint.

Objective: To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome., Methods: pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions., Results: Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03)., Conclusion: Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response.

Objective: To assess the magnetic resonance imaging (MRI) and ultrasound (US) changes in the wrist of patients with rheumatoid arthritis (RA) 4 weeks after an US guided intraarticular (IA) injection., Methods: Contrast enhanced MRI and US-Doppler were performed at baseline and 4 weeks after IA injection of either 40 mg methylprednisolone (n = 12) or 25 mg etanercept (n = 13) in 25 patients with RA taking disease modifying antirheumatic drugs with a therapy-resistant wrist joint. All injections were US guided., Results: There was an improvement in swollen target joint score (p < 0.001), tender target joint score (p < 0.002), and physician visual analog scale score (p < 0.001) after 4 weeks. Baseline MRI synovitis score was mean 5.08 (range 3-9) and was unchanged at followup in the whole group (p = 0.52) and between treatment groups (p = 0.43). MRI edema score (mean 4.46, range 0-29) in the total group was unchanged after 4 weeks (p = 0.13), whereas MRI erosion score increased in the total group from baseline, 17.88 (range 7-40), to 4 weeks, 18.25 (range 7-40) (p < 0.001). Neither US-Doppler color fraction (0.07) nor Resistive Index (RI) (p = 0.36) changed from baseline to 4 week followup., Conclusion: In contrast to the clinical evaluation, imaging measures of relevance for the estimation of inflammation, US-Doppler, US RI, MRI synovitis, and bone-marrow edema did not change 4 weeks after a single IA injection of either methylprednisolone or etanercept in the wrist. Within the same period, erosive progression in some patients suggested that joints with active disease may deteriorate within as little as 1 month, and that this development is not arrested by 1 injection. Given the small sample size of our study further studies are required to confirm our results.

A fully automated method for quantitative analysis of dynamic contrast-enhanced MRI data acquired with low and high field scanners, using spin echo and gradient echo sequences, depicting various joints is presented. The method incorporates efficient pre-processing techniques and a robust algorithm for quantitative assessment of dynamic signal intensity vs. time curves. It provides differentiated information to the reader regarding areas with the most active perfusion and permits depiction of different disease activity in separate compartments of a joint. Additionally, it provides information on the speed of contrast agent uptake by various tissues. The method delivers objective and easily reproducible results, which have been favourably viewed by a number of medical experts.

Signs of inflammation and destruction in the finger joints are the principal features of rheumatoid arthritis (RA). There are few studies assessing the sensitivity and specificity of ultrasonography in detecting these signs. The objective of the present study was to investigate whether ultrasonography can provide information on signs of inflammation and destruction in RA finger joints that are not available with conventional radiography and clinical examination, and comparable to the information provided by magnetic resonance imaging (MRI). The second to fifth metacarpophalangeal and proximal interphalangeal joints of 40 RA patients and 20 control persons were assessed with ultrasonography, clinical examination, radiography and MRI. With MRI as the reference method, the sensitivity, specificity and accuracy of ultrasonography in detecting bone erosions in the finger joints were 0.59, 0.98 and 0.96, respectively; they were 0.42, 0.99 and 0.95 for radiography. The sensitivity, specificity and accuracy of ultrasonography, with signs of inflammation on T1-weighted MRI sequences as the reference method, were 0.70, 0.78 and 0.76, respectively; they were 0.40, 0.85 and 0.72 for the clinical examination. With MRI as the reference method, ultrasonography had higher sensitivity and accuracy in detecting signs of inflammation and destruction in RA finger joints than did clinical and radiographic examinations, without loss of specificity. This study shows that ultrasonography has the potential to improve assessment of patients with RA.

Objective: To compare the relationship between bone mineral density (BMD) in the metacarpal bones and forearm measured by dual X-ray absorptiometry (DXA) and digital X-ray radiogrammetry (DXR) and radiological alterations in patients with early and established rheumatoid arthritis (RA)., Patients and Methods: In each of the three disease duration groups, 11 female RA patients were included. The patients were further divided into two groups according to bone erosions. BMD in the metacarpals was evaluated by DXA and DXR., Results: A significant relationship between DXA-BMD and DXR-BMD was observed. DXR-BMD and the individually combined cortical thickness (CT) of the metacarpo-phalangeal (MCP) joints were related to disease duration and erosions. Patients with erosive disease had lower values of age- and sex-adjusted BMD measured with DXA, but most significantly with DXR., Conclusion: DXR appears to be a more sensitive method than DXA in detecting early bone loss in patients with RA. The relationship of DXR-BMD to disease duration and bone damage indicates that the DXR method may be useful in the evaluation of disease activity and progression.

Objective: To assess the applicability of serum concentrations of markers of synovial inflammation, cartilage, and bone metabolism in relation to conventional markers of disease activity, bone mineral density (BMD) of the hand, and radiographic outcome., Methods: Biochemical markers of collagen tissue metabolism were measured in 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least 4 weeks and less than 2 years. At 2 years, 51 patients fulfilled the American College Rheumatology criteria for rheumatoid arthritis (RA) and 21 patients had unclassified polyarthritis. Patients with RA were divided into groups according to the mean disease activity and to magnetic resonance imaging and radiographically detected bone erosions in the hands., Results: Patients with RA had significantly higher serum concentrations of matrix metalloproteinase-3 (MMP-3) at baseline and higher mean concentrations of serum MMP-3 and pyridinoline (Pyd) during the first 6 and 12 months than patients with unclassified polyarthritis. RA patients with persistent disease activity and erosive disease had significantly higher concentrations of serum MMP-3 and Pyd than patients with no disease activity or nonerosive disease. Significant mutual correlations between serum MMP-3 and Pyd and C-reactive protein and erythrocyte sedimentation rate were observed. The mean values of MMP-3 and Pyd correlated significantly to the alpha coefficient of the digital x-ray radiogrammetry (DXR-BMD)., Conclusion: Serum MMP-3 and Pyd varied according to disease activity, periarticular osteoporosis measured by DXR, and radiographic outcome, and thus appear to supplement the conventional markers of disease activity for monitoring patients with RA.

Objective: In a 5-year followup study, we investigated the temporal relationship between development of wrist joint erosions as visualized by magnetic resonance imaging (MRI) versus conventional radiography (CR), in patients with rheumatoid arthritis. We also evaluated the risk of erosive progression on CR associated with the presence of MRI erosions., Methods: In 10 patients with rheumatoid arthritis, MRI and CR of the dominant wrist were performed annually for 5 years. In each image set, each wrist bone (metacarpal bases, carpal bones, radius, and ulna) was assessed for the absence or presence of bone erosions., Results: Nine bones showed radiographic erosions at baseline. Twenty-seven new radiographic erosions developed during the 5-year followup period. Of these 27 new erosions, 21 were detected 1-5 years earlier by MRI than by CR, 3 were simultaneously detected by both methods, 2 were detected 1-2 years later by MRI than by CR, and 1 erosion (radiographically detected at 5-year followup) was not visualized with MRI. MRI detection of new radiographic erosions preceded CR detection by a median of 2 years. In bones with MRI erosions at baseline, the relative risk of radiographic erosions at 5-year followup was 4.5 (95% confidence interval [95% CI] 2.6-7.6), compared with bones without baseline MRI erosions. If bones with baseline radiographic erosions were excluded from the analysis, the relative risk was 4.1 (95% CI 2.2-7.5)., Conclusion: Most new radiographic bone erosions (78%) were visualized at least 1 year earlier by MRI than by CR. This illustrates that the information on joint destruction provided by CR is considerably delayed compared with that provided by MRI. A significantly increased risk of progression of radiographic erosion in bones with baseline MRI erosions was observed, demonstrating a prognostic value of MRI with respect to long-term radiographic outcome.

To evaluate MRI for assessment of inflammation, destruction and prognosis in rheumatoid arthritis (RA), 26 RA patients, randomized to disease-modifying anti-rheumatic drug (DMARD) therapy alone or in combination with oral prednisolone, were followed for one year with contrast-enhanced MRI of the dominant wrist (months zero, three, six and 12), conventional radiography and clinical and biochemical examinations. Significant synovial membrane volume reductions were observed in both groups, earliest in the DMARD + prednisolone group. The rate of erosive progression on MRI was highly correlated with baseline and area-under-curve (AUC)-values of synovial membrane volume, but not with baseline or AUC-values of local or global clinical or biochemical parameters, nor with +/- prednisolone. MRI was more sensitive than radiography as regards detection of progressive bone destruction (22 versus 12 new bone erosions). MRI may prove valuable as marker of joint disease activity and destruction and, perhaps, prognosis in RA.

Objectives: To evaluate synovial membrane hypertrophy, tenosynovitis, and erosion development of the 2nd to 5th metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints by magnetic resonance imaging in a group of patients with rheumatoid arthritis (RA) or suspected RA followed up for one year. Additionally, to compare the results with radiography, bone scintigraphy, and clinical findings., Patients and Methods: Fifty five patients were examined at baseline, of whom 34 were followed up for one year. Twenty one patients already fulfilled the American College of Rheumatology (ACR) criteria for RA at baseline, five fulfilled the criteria only after one year's follow up, whereas eight maintained the original diagnosis of early unclassified polyarthritis. The following MRI variables were assessed at baseline and one year: synovial membrane hypertrophy score, number of erosions, and tenosynovitis score., Results: MRI detected progression of erosions earlier and more often than did radiography of the same joints; at baseline the MRI to radiography ratio was 28:4. Erosions were exclusively found in patients with RA at baseline or fulfilling the ACR criteria at one year. At one year follow up, scores of MR synovial membrane hypertrophy, tenosynovitis, and scintigraphic tracer accumulation had not changed significantly from baseline; in contrast, swollen and tender joint counts had declined significantly (p<0.05)., Conclusions: MRI detected more erosions than radiography. MR synovial membrane hypertrophy and scintigraphy scores did not parallel the changes seen over time in clinically assessed swollen and tender joint counts. Although joint disease activity may be assessed as quiescent by conventional clinical methods, a more detailed evaluation by MRI may show that a pathological condition is still present within the synovium.

Purpose: To elaborate the best MR imaging protocol for studies in rheumatoid arthritis (RA) and to evaluate the sensitivity and interobserver agreement with respect to detection of bone erosions (MR and radiography) and grading of synovial membrane hypertrophy (MR imaging only)., Material and Methods: MR imaging and conventional radiography of wrist and metacarpophalangeal (MCP) joints were performed in 41 RA patients and 3 healthy controls. The following pulse sequences were applied: T1-weighted spin-echo (T1-SE) with and without contrast enhancement, T2-SE, T2-turbo-SE, T1-2D-FLASH, T1-3D-FLASH, fat-saturated-T1-SE, STIR and 3D-DESS., Results: Bone erosions were found by MR compared to radiography in 261 versus 85 bones of the wrist (ratio 3.1) and 59 versus 21 MCP joint quadrants (ratio 2.81). MR and radiography interobserver agreements were both approximately 90%. Likewise, MR scored synovial membrane hypertrophy in wrist and MCP joints with a high interobserver agreement. The most informative MR sequence appeared to be contrast-enhanced T1-SE MR, preferably with fat saturation. A STIR sequence or T2-weighted fat saturation sequence was useful in screening for joint disease., Conclusion: The sensitivity of MR is superior to conventional radiography with respect to detection of bone erosions in wrist and MCP joints. The interobserver agreement for MR and radiography was similar. Thus, MR of wrist and finger joints may become a useful supplement to conventional radiography in the evaluation of RA patients in clinical trials and clinical practice.

Objective: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA)., Methods: Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed., Results: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions)., Conclusion: MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.