Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: a comparative study

OBJECTIVE: To compare the quantitative and qualitative information obtained by Doppler ultrasound (US) measurements of the wrist joints and the small joints of the hand with the information obtained by postcontrast magnetic resonance imaging (MRI) and to correlate the imaging results with clinical observations in patients with rheumatoid arthritis (RA). METHODS: Twenty-nine consecutive RA patients were studied; 196 joints (29 wrist and 167 finger joints) were examined by both US and MRI. Parameters of inflammation were the color fraction and the resistance index (RI) obtained with color Doppler US and the thickness of enhanced synovium (in mm) and the MRI score obtained with postcontrast MRI. Clinical examination and measurements of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were performed on the same day as the imaging studies. RESULTS: There was a highly significant association between US indices of inflammation and postcontrast MRI scores. The mean values for both the color fraction and the RI were significantly different in the group without joint swelling compared with the other groups. The mean RI values were significantly different in the group without joint tenderness compared with the other groups. The mean thickness of enhanced synovium on postcontrast MRI was significantly different between the group without joint swelling and the other groups, but this difference was statistically significant only for the comparison of the group without joint tenderness versus the group with maximum tenderness. No association between the MRI or US estimates of inflammation and values on the visual analog scale for pain, Health Assessment Questionnaire, duration of morning stiffness, ESR, or CRP was found. CONCLUSION: Estimates of synovial inflammatory activity by Doppler US and postcontrast MRI were comparable. Estimation of synovial inflammatory activity by the RI and color fraction parameters of US appears to be a promising method of detecting and monitoring inflammatory activity in patients with RA.     

Magnetic resonance imaging of the craniovertebral junction in rheumatoid arthritis

Conventional radiography and magnetic resonance imaging (MRI) of the craniovertebral junction were evaluated in 12 patients with longstanding rheumatoid arthritis (RA) and neck pain with or without other neurologic signs or symptoms of cervical myelopathy. MRI demonstrated abnormal soft tissue masses thought to represent pannus in 9 patients. Three patients showed cord or brainstem compression due to pannus or atlantoaxial subluxation. The 3 patients with MRI evidence of cord or brainstem compression had neurologic signs or symptoms of cervical myelopathy, and appropriate therapy was instituted based on these findings. This study indicates that MRI is able to detect abnormal soft tissue masses which probably represent pannus and their relationship to the spinal cord or brainstem, and confirms the utility of the procedure in the management of craniovertebral involvement in RA.     

Magnetic resonance imaging for the study of cervical myelopathy in rheumatoid arthritis

Cervical myelopathy is found fairly often with rheumatoid arthritis. It is one of the worst complications of the disease and can lead to tetraplegia or even to sudden death. However, when we consider the high incidence of involvement of the cervical spine in rheumatoid arthritis, the number of cases of cervical myelopathy, even of slight degree, is not very high. We have used magnetic resonance to identify the condition of the cervical structures, especially the nerve structures, in 15 patients with rheumatoid arthritis, with involvement of the cervical articulations but without neurological symptoms. We found anterior compression of the spinal cord caused by the odontoid process of the epistropheus in 13 cases. One case had lateral deviation of the spinal cord and another had compression of a vertebral artery. In another the lumen of the nasopharynx was decreased and one had posterior compression of the spinal cord by the posterior arch of the atlas. Magnetic resonance also makes it possible to detect a rheumatoid pannus on the affected articulations. We conclude that magnetic resonance is at present a useful instrument for evaluation of the presence of cervical myelopathy in rheumatoid arthritis patients, to prevent more serious complications.     

Magnetic resonance imaging in early rheumatoid arthritis: a multicenter,prospective study

To identify the magnetic resonance imaging (MRI) features of hands and wrists in early rheumatoid arthritis (RA). A total of 129 early arthritis patients (≤1 year) were enrolled in the study. At presentation, MRI of the hands was performed, with clinical and laboratory analyses. After a 1-year follow-up, clinical diagnosis of early RA or non-RA was confirmed by two rheumatologists. The characteristics of MRI variables at baseline in RA patients not fulfilling ACR 1987 criteria [RA-87(?)] were compared with those fulfilling ACR1987 criteria [RA-87(+)] and non-RA. In the 129 early arthritis patients, 90 were diagnosed with RA in a 1-year follow-up. There were 47.8 % (43/90) of the RA patients not fulfilling ACR 1987 criteria [RA-87(?)]. The scores of synovitis in RA-87(?) patients were similar with those in RA-87(+) [Synovitis score, 14.0 (IQR, 4.0–25.0) vs. 14.0 (IQR, 10.0–25.0), p?>?0.05]. Compared with those in non-RA, RA-87(?) patients had higher synovitis scores and occurrence of synovitis in proximal interphalangeal (PIP) joints [synovitis score, 14.0 (IQR, 4.0–25.0) vs. 6.0 (IQR, 2.0–14.5), p?=?0.046; occurrence of PIP synovitis: 53.5 vs. 27.3 %, p?=?0.02]. There was no significant difference of bone marrow edema, bone erosion, and tenosynovitis between RA-87(?) and non-RA. Synovitis in PIP joints was independent predictor for RA-87(?) [OR, 3.1 (95 %CI 1.2–8.1)]. High synovitis scores and synovitis in PIP joints on MRI were important in early RA, especially those not fulfilling ACR 1987 criteria.     

Magnetic resonance imaging of articular destruction in juvenile rheumatoid arthritis

We describe herein magnetic resonance imaging of the right knee of a patient affected by a severe form of juvenile rheumatoid arthritis. Magnetic resonance imaging findings of articular damage of the knee during the disease course and after arthroscopic synovectomy are described.     

Magnetic resonance imaging in rheumatoid arthritis advances and research priorities

This article updates the work and results of the OMERACT MRI in RA Working Group as presented at the OMERACT 7 meeting in May 2004, focusing on the development of the EULAR-OMERACT rheumatoid arthritis magnetic resonance imaging reference image atlas, and on areas for future research.     

Magnetic resonance imaging and miniarthroscopy of metacarpophalangeal joints: Sensitive detection of morphologic changes in rheumatoid arthritis

Objective

To evaluate and characterize magnetic resonance imaging (MRI) findings in the metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients macroscopically, using miniarthroscopy (MA; needle arthroscopy).

Methods

The second MCP joint of the dominant hand of 22 RA patients (13 with various RA activities/stages; 9 with early RA [≤1.5 years' duration]) was examined by MRI followed by MA. Findings were evaluated by standardized semiquantitative measures of synovial and bony pathologic changes of the MCP joint, and were compared with the clinical and conventional radiologic findings.

Results

Erosions and pre‐erosions were detected in 17 of 22 patients by MRI; 2 of the other 5 patients (all early RA) displayed bony changes on MA. All 10 joints with pre‐erosions on MRI (grade I bony alterations on MRI) exhibited significant cartilaginous and bony pathology on MA. Synovial membrane pathology was detected in all but 1 patient by MRI and in all patients by MA, although findings of plain radiography were normal in 6 of the 22 patients and another 9 patients had a Larsen score of 1. Semiquantitative analysis of synovial findings of MRI revealed gadolinium diethylenetriaminepentaacetic acid enhancement as a significant marker of macroscopically varied synovial vascularity and hyperemia, both of which strongly correlated with clinical activity (as measured by the Disease Activity Score). The extent of synovitis/synovial proliferation shown by MA and MRI were significantly correlated with each other, but not with any other activity or damage parameter analyzed.

Conclusion

In RA, both MRI and MA findings support early detection and staging of synovial changes. Ongoing longitudinal studies are aimed at evaluating the value of synovial proliferation as visualized by both methods.

     

Magnetic resonance imaging in rheumatoid arthritis: current status and future directions

The performance of alternative imaging endpoints in clinical trials can be compared in terms of validity, rate of change, measurement precision, and convenience and cost. With respect to technical performance, magnetic resonance imaging (MRI) appears to show greater sensitivity than radiography for detecting bone abnormalities in rheumatoid arthritis (RA). In addition to monitoring changes in the bones, cartilage, and synovium, MRI can directly visualize the full spectrum of tendon pathology, and has been shown to identify tendonitis and tendon rupture with greater accuracy than clinical examination. MRI is currently regarded to be the most sensitive imaging technique for identifying trauma, infection, ischemia, and primary and secondary neoplasia of bone. Several studies have also shown MRI to be highly sensitive for detecting what appear to be bone erosions in the hands and wrists of patients with RA. MRI shows remarkable promise as a tool for identifying and monitoring structural damage in the joints of patients with RA. MRI appears to be able to identify bone erosions with greater sensitivity than radiography, and to disclose edema-like changes in the marrow, which may precede actual erosion formation. As new therapies with structure modifying capabilities enter the clinic, the ability to identify patients appropriate for those therapies and then to monitor the effectiveness and safety of treatment become increasingly important.     

Magnetic resonance imaging of the shoulder in patients with rheumatoid arthritis.

To evaluate the ability of magnetic resonance imaging (MRI) to detect shoulder abnormalities 18 patients (36 shoulders) with rheumatoid arthritis (RA) and shoulder complaints were studied. Osseous abnormalities of the glenoid and humeral head were readily detected with MRI. The imaging planes used were not suitable for the evaluation of acromioclavicular joint involvement. Magnetic resonance imaging depicted soft tissue abnormalities that were not clearly visualised by plain film radiography, such as involvement of rotator cuff tendons and subacromial bursae, joint effusion, and muscular atrophy. Magnetic resonance imaging appears to be a sensitive method for evaluation of glenohumeral joint changes in patients with RA.     

Magnetic resonance imaging and miniarthroscopy of metacarpophalangeal joints: sensitive detection of morphologic changes in rheumatoid arthritis.

OBJECTIVE: To evaluate and characterize magnetic resonance imaging (MRI) findings in the metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients macroscopically, using miniarthroscopy (MA; needle arthroscopy). METHODS: The second MCP joint of the dominant hand of 22 RA patients (13 with various RA activities/stages; 9 with early RA [< or = 1.5 years' duration]) was examined by MRI followed by MA. Findings were evaluated by standardized semiquantitative measures of synovial and bony pathologic changes of the MCP joint, and were compared with the clinical and conventional radiologic findings. RESULTS: Erosions and pre-erosions were detected in 17 of 22 patients by MRI; 2 of the other 5 patients (all early RA) displayed bony changes on MA. All 10 joints with pre-erosions on MRI (grade I bony alterations on MRI) exhibited significant cartilaginous and bony pathology on MA. Synovial membrane pathology was detected in all but 1 patient by MRI and in all patients by MA, although findings of plain radiography were normal in 6 of the 22 patients and another 9 patients had a Larsen score of 1. Semiquantitative analysis of synovial findings of MRI revealed gadolinium diethylenetriaminepentaacetic acid enhancement as a significant marker of macroscopically varied synovial vascularity and hyperemia, both of which strongly correlated with clinical activity (as measured by the Disease Activity Score). The extent of synovitis/synovial proliferation shown by MA and MRI were significantly correlated with each other, but not with any other activity or damage parameter analyzed. CONCLUSION: In RA, both MRI and MA findings support early detection and staging of synovial changes. Ongoing longitudinal studies are aimed at evaluating the value of synovial proliferation as visualized by both methods.     

Magnetic resonance imaging applications in early rheumatoid arthritis diagnosis and management

Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is a sensitive modality that can assess both inflammatory and structural lesions. MRI can assist in following the disease course in patients treated with traditional disease-modifying antirheumatic drugs and biological therapies both in the clinic and in research trials. Therefore, it is anticipated that MRI becomes the diagnostic imaging modality of choice in RA clinical trials while remaining a useful tool for clinicians evaluating patients with RA.     

Magnetic resonance imaging of rheumatoid arthritis: the evolution of clinical applications through clinical trials

Powerful techniques are being developed for evaluating rheumatoid arthritis with magnetic resonance imaging (MRI). Much of this development is being driven by the pharmaceutical and biotechnology industries searching for novel therapies for this disease. Accordingly, the imaging tools that ultimately will be used to direct patients to specific therapies and then to monitor treatment effectiveness and safety are currently being refined and validated in rigorous multicenter and multinational clinical trials aimed at gaining regulatory approval of these new therapies. As these trials approach completion, rheumatologists can anticipate an increased demand for expertise and experience in evaluating disease progression and treatment response with these techniques and the emergence of MRI systems specifically designed for this market. The following discussion reviews this novel pathway for evolving imaging techniques for clinical use through clinical drug trials, lists the most promising MRI markers available today for evaluating joint destruction in rheumatoid arthritis, and speculates on how these techniques will find their way into clinical practice.     

Chemokines in synovial inflammation in rheumatoid arthritis: basic and clinical aspects

Abstract

The mechanism by which anti-DNA antibodies cause glomerulonephritis in systemic lupus erythematosus (SLE) has not been fully elucidated. However, not a few recent studies suggest the pivotal role of nucleosomal histones in the binding of immune complexes to the glomerular basement membrane. Some antibodies cross-react with both double-stranded (ds) DNA and nucleosome, but antibodies exclusively specific to the nucleosome have also been described. In lupus model mice, anti-nucleosome antibodies are reported to emerge even before the production of anti-dsDNA antibodies. BK virus T antigen, bacterial DNA, a DNA binding protein nucleobindin and autoreactive helper T cells specific to nucleosome or anti-DNA antibody-derived peptides have been shown to induce or enhance anti-DNA antibody production in normal or lupus-prone animals. These new experimental models are expected to be helpful in the exploration of the true antigen that elicits autoimmune reactions in SLE.     

Chemokines in synovial inflammation in rheumatoid arthritis: basic and clinical aspects

 Rheumatoid arthritis (RA) is a chronic, multisystem autoimmune disease characterized by persistent synovitis. Since chemotactic cytokines (chemokines) may play critical roles in the recruitment of leukocytes in RA, analyses of chemokines and their receptors should provide insight into events in synovial inflammation in RA. The production of chemokines is regulated by cytokines such as tumor necrosis factor (TNF)-α produced in the inflamed joint, suggesting that the efficacy of anti-TNF-α therapy is mediated at least partly by the reduction of chemokine production. Chemokines have a role in joint inflammation not only by inducing leukocyte chemotaxis, but also by activating immune cells and angiogenesis. The pathogenesis of RA has been shown to be mediated by Th1-type T cells, because Th1-related chemokine receptors are preferentially expressed on cells in synovial fluid and synovial tissue. Accordingly, antichemokine therapy may be important as a possible new approach to therapeutic intervention in RA.     

Magnetic resonance imaging appearance of the hands and feet in patients with early rheumatoid arthritis

OBJECTIVE: To describe the magnetic resonance (MRI) imaging findings of the feet in patients with early rheumatoid arthritis (RA), and to compare MRI appearance of the feet with that of the hands. METHODS: Thirty consecutive patients (18 women, 12 men; age range 19-64 yrs) with early RA underwent MRI of hands and feet. Axial fat suppressed gadolinium enhanced T1 weighted spin-echo and gadolinium enhanced 3-dimensional gradient-echo (FLASH) images were obtained. RESULTS: In the hands, MRI findings suggested active synovitis of the wrist and metacarpophalangeal (MCP) joints in 28 (93%) and 27 (90%) patients, respectively. In the feet, active synovitis was observed in 29 (97%) patients. Bone erosions were seen in the wrist joints in 24 (80%) patients. Observers found as many bony changes in the MCP as in the metatarsophalangeal joints [23 (77%) patients]. MRI detected tenosynovitis in 16 (53%) patients in the hands, and in 18 (60%) patients in the feet. Bursitis located between or beneath the metatarsal heads was a common MRI finding [19 (63%) patients]. CONCLUSION: Additional MRI of the feet may be useful when evaluation of the hands does not help identify early RA.     

Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis

OBJECTIVE: Density of sympathetic nerve fibers in synovial tissue was lower in patients with rheumatoid arthritis (RA) compared to those with osteoarthritis (OA). This was accompanied by norepinephrine (NE) release from synovial tyrosine hydroxylase positive cells (TH+ cells). We investigated the role of TH+ cells and NE in synovial inflammation. METHODS: Synovial tissue of 34 patients with RA and 36 with OA who underwent knee joint replacement surgery was characterized using immunohistochemistry and a synovial tissue superfusion technique, respectively. In culture experiments with mixed synoviocytes, the effect of NE on secretion of interleukin 6 (IL-6), IL-8, tumor necrosis factor (TNF), and matrix metalloproteinase-3 (MMP-3) was investigated. RESULTS: Tissue density of TH+ cells was higher in RA compared to OA (63.9 vs 34.2 cells/mm2; p = 0.017). Basal NE release from synovial tissue correlated highly significantly with density of TH+ cells in RA (Rrank = 0.573, p = 0.001) but not in OA (Rrank = 0.102, NS). Basal NE release correlated with the degree of inflammation in RA (Rrank = 0.420, p = 0.021) but not in OA (Rrank = 0.174, NS), and with spontaneous IL-8 secretion in RA (Rrank = 0.581, p = 0.001) but not in OA (Rrank = 0.160, NS). Only in RA, density of TH+ cells correlated positively with spontaneous secretion of IL-6, IL-8, and MMP-3. We confirmed the extensive loss of sympathetic nerve fibers in RA compared to OA (0.32 vs 3.1 nerve fiber/mm2; p < 0.001). The ratio of sympathetic to sensory nerve fibers was 1 to 5 in RA and 2 to 1 in OA. A ratio of 1.0 separates almost all patients into 2 diseases groups (RA vs OA). Prior prednisolone treatment of RA patients was related to decreased spontaneous cytokine secretion, a lower density of T cells, CD163+ macrophages and TH+ cells, a lower degree of inflammation, and reduced synovial NE secretion. NE was able to inhibit secretion of IL-6 (in OA), IL-8 (in RA), and TNF (in RA and OA) in culture experiments. CONCLUSION: TH+ cells and release of NE are strongly linked to a higher degree of synovial inflammation. Culture experiments indicate that NE has antiinflammatory properties at higher concentrations (10(-5) M). NE secretion of TH+ cells may be an antiinflammatory mechanism to counteract local inflammation. Thus, TH+ cell derived NE can be an important local factor of immunomodulation in synovial inflammation.