Advances in Imaging of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common of the inflammatory arthropathies, affecting nearly 1% of the population with a female preponderance. Onset is typically between 45 and 65 years of age. While the etiology RA is unknown, it is thought to be largely autoimmune. Lack of treatment results in rapid progression of disease with significant joint destruction, pain, and loss of function.

The diagnosis of rheumatoid arthritis relies upon a well- established list of criteria that encompasses clinical, laboratory, and imaging data. The 1987 diagnostic criteria of the American College of Rheumatology (ACR) includes: morning stiffness of at least 1 hour, soft tissue swelling of three or more joints, arthritis of proximal hand joints (MCP, PIP, or carpal joints), symmetric joint swelling, subcutaneous rheumatoid nodules, positive rheumatoid factor, and radiographic evidence of disease (erosions or periarticular bone resorption). At least four of these criteria must be met. The requirement for so many criteria belies the difficulty in diagnosing RA early in the disease process. There is no single test that unequivocally establishes the diagnosis.

In rheumatoid arthritis, the primal pathologic process is centered in the synovium. This may be within joints, around tendons, or within bursae. Synovial hyperplasia (thickening) with pannus formation is the fundamental pathogenesis of RA. The resulting cascade of hyperemia and synovial proliferation leads to bone resorption (osteopenia), bone destruction (erosions), and cartilage destruction (joint space narrowing). Rapidly arresting this synovial inflammatory cascade using biologic agents and disease modifying antirheumatic drugs (DMARDS) is the central aim of therapy for rheumatoid arthritis. Toward this end, the refinement of imaging modalities to rapidly assess a patient’s response to an administered DMARD or biologic agent is a central focus of clinical rheumatoid research.

X-Rays

Historically, plain film radiography has been important in the evaluation of RA disease course. Progression of disease is recognized as radiographic progression over time, with worsening erosions, joint space narrowing, and deformity. Methodologies to score the radiographic damage were developed to provide more quantitative assessment of disease progression. The Sharp method is the most commonly used method. Initially, this method included AP radiographs of both hands and wrists and evaluated several bone changes including cortical thinning, osteoporosis, sclerosis, periosteal reaction, osteophytes, cystic changes, joint space narrowing, erosions, and ankylosis. Eventually the method was changed to only include two scores, one for erosions and a second for joint space narrowing. The van der Heijde modification of the Sharp score further refined the system. In the final van der Heijde modification, the erosion score and joint space narrowing score includes the hands, wrists, and feet at defined joint locations. The total radiographic score ranges from 0 to 448. Each joint location is given an erosion score from 0 to 5 and a joint space narrowing score from 0 to 4.

Although radiographs remain central to the diagnosis and long-term management of rheumatoid arthritis, they are limited in their ability to detect rapid changes in clinical status and disease activity. Modern therapy for RA focuses on prompt clinical response to biologic agents and DMARDs to prevent further joint damage. Unfortunately, once there are radiographic signs of disease progression, irreversable joint destruction has already occurred. Alternative imaging modalities such as magnetic resonance imaging (MRI) and ultrasound (US) are now finding roles in the early diagnosis of RA as well as assessing progression of disease before the advent of bone destruction.

Magnetic Resonance Imaging

Magnetic resonance imaging is the most sensitive modality for detecting the earliest changes of rheumatoid arthritis. Small field of view images of the hands and wrists are obtained with dedicated surface coils to maximize image detail. The stronger the magnet, the better the anatomic detail, with high field 3 Tesla magnets providing an incrementally better anatomic picture as compared to 1.5 Tesla machines. The Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) MR imaging study group has attempted to standardize techniques and scoring systems for MR imaging of RA. The MR imaging studies require two-plane (coronal and axial) T1 weighted images, two-plane fluid sensitive sequences (either fat-saturated T2 or STIR), and two-plane gadolinium enhanced fat-saturated T1 weighted images. Synovitis is the earliest finding in RA. Normally, synovial tissue is too thin to be visible on routine MR images. With synovitis, the synovium will thicken, show increased signal on T2 images, and enhance avidly after gadolinium administration. The OMERACT group defines synovitis as an area in the synovial compartment with increased enhancement whose thickness exceeds the width of the normal synovium. The OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) assesses synovitis in three wrist and hand regions and scores synovitis from zero (normal) to three (severe). MR has been shown to be more accurate in the evaluation of synovitis as compared to clinical evaluation.

Bone marrow edema is a distinctive and important finding in MR imaging of RA. It presents as high signal intensity on T2 images and low signal intensity on T1 weighted images. It does enhance after gadolinium administration. The OMERACT group defines bone edema as a lesion in the trabecular bone that has ill-defined margins and signal intensity characteristics consistent with increased water content. It may be seen alone or surrounding an erosion or other bone abnormality. Bone marrow edema is considered a precursor of erosive disease and is therefore an important marker of inflammation. It is considered reversible with effective DMARD therapy. According to RAMRIS, bone marrow edema is scored on a scale of 0 to 3 on the basis of volume of edema.

MR is much more sensitive to the detection of erosions as compared to conventional radiography. The OMERACT group defines erosions as sharply marginated bone lesions adjacent to a joint with a cortical break seen in at least one plane. The lesions are low signal on T1 images, high signal on T2 images, and enhance due to the presence of inflamed synovium in the lesion. The OMERACT RAMRIS scores erosions from 1-10 based upon the volume of the erosion with respect to the assessed bone.

Ultrasound Imaging

Ultrasound imaging has made great strides in the imaging of early rheumatoid arthritis. In grey scale, ultrasound detects the morphologic changes of synovitis with synovial thickening and hypertrophy. Synovial thickening is typically heterogeneously hypoechoic as compared to the adjacent subdermal fat. It does show blood flow whereas joint effusion does not. The OMERACT Ultrasound Task Force has defined a greyscale scoring system for synovitis. Grade zero is normal synovial thickness, grade one is synovial thickening that does not bulge over the tops of the bones, Grade two bulges over the tops of the bones, while grade three bulges over and extends along one of the bone diaphyses. The major shortcoming of ultrasound is its user dependence, but this shortcoming is becoming less pronounced as imaging protocols become standardized and ultrasound practitioners become more experienced.

In Power Doppler mode, ultrasound provides another means to assess synovitis. Synovial inflammation results in synovial hyperemia. Power Doppler is exquisitely sensitive to the presence of blood flow in tissue. The OMERACT Ultrasound Task Force has developed a grading system for Doppler signal. Grade 0 is no flow in the synovium, grade one is up to three single spots in the synovium, grade 2 is signal in less than 50% of synovial area, while grade three is signal in over 50% of synovium. Ultrasound also provides a role in detecting other findings in rheumatoid arthritis such as joint effusions, erosions, bursitis, and tenosynovitis.

Summary

Imaging plays a central role in the diagnosis and management of rheumatoid arthritis. While plain film radiography is the historical gold standard in imaging assessment of disease progression, both ultrasound and MRI have made great strides in imaging the anatomic changes in rheumatoid arthritis. Both ultrasound and MRI allow for earlier detection of disease, before irreversible damage to joints has occurred. As clinical management continues to shift toward earlier detection of disease and aggressive therapeutic management, these imaging modalities will play a greater role in both disease diagnosis as well as the rapid assessment of response to DMARDs and biologic agents. The OMERACT MR and Ultrasound task forces continue to refine scoring systems for quantifying the changes seen in rheumatoid arthritis. Established imaging scoring systems will allow a more uniform approach to determining the effectiveness of therapies targeted to rheumatoid arthritis, both in the clinical and research arenas.

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Volume 6, Issue 5: Guidance for Sponsors: Advances in Imaging of Rheumatoid Arthritis

Originally written by legacy Intrinsic Imaging Medical Director