Rheumatoid Arthritis: Ultrasound Versus MRI

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1 Musculoskeletal Imaging Review Rowbotham and Grainger Imaging Rheumatoid Arthritis Musculoskeletal Imaging Review FOCUS ON: Emma L. Rowbotham 1 Andrew J. Grainger Rowbotham EL, Grainger AJ Keywords: erosions, rheumatoid arthritis, synovitis DOI: /AJR Received March 4, 2011; accepted after revision May 19, Both authors: Department of Radiology, Chapel Allerton Hospital, Leeds, LS7 4SA, United Kingdom. Address correspondence to A. J. Grainger (andrew.grainger@leedsth.nhs.uk). AJR 2011; 197: X/11/ American Roentgen Ray Society Rheumatoid Arthritis: Ultrasound Versus MRI Objective. Rheumatoid arthritis is a predominantly joint-based disease affecting approximately 1% of the world s population. This article will address the increasing use of both ultrasound and MRI in the diagnosis and monitoring of rheumatoid arthritis and will highlight both the strengths and weaknesses of these two imaging modalities, with particular reference to bone erosions and synovitis. Conclusion. Because they can detect early disease, both ultrasound and MRI will become increasingly important in the diagnosis and management of rheumatoid arthritis. Future studies with increased patient numbers will be necessary if one of these two modalities is to emerge as a clear winner as the imaging modality of choice. R heumatoid arthritis is a predominantly joint-based disease affecting approximately 1% of the world s population. It is a chronic systemic autoimmune disorder that primarily affects the synovium and if left untreated leads to disorganization and destruction of the joints. In turn, joint destruction results in severe deformity and disability. Synovial hypertrophy and angioneogenesis develop in the chronic phase of the condition, the hypertrophied synovium becoming locally invasive at the synoviumcartilage interface where it is thought to be responsible for causing bone erosions and subsequent joint destruction. Radiographs have traditionally been the mainstay for imaging patients with rheumatoid arthritis; findings such as soft-tissue swelling, periarticular osteopenia, joint space loss, joint subluxation, and marginal erosions are all features that may be seen. However, information regarding the synovium is much more difficult to assess on radiographs. Up until recent advances in medical management of rheumatoid arthritis, radiographic diagnosis and follow-up of the condition were considered adequate. With the increasing use of disease-modifying antirheumatic drugs, early diagnosis is now of paramount importance and disease progression is assessed regularly to monitor efficacy of the treatment. The introduction of these new therapies has placed increased importance on imaging, particularly on the identification of early changes, with the emphasis now on early diagnosis and treatment of rheumatoid arthritis before irreversible joint damage occurs [1]. In 1987, radiographic erosions were included in the diagnostic criteria for rheumatoid arthritis by the American College of Rheumatology and were thought to be both sensitive and specific for the condition [2]. However, patients increasingly present with a presumed early-stage diagnosis of rheumatoid arthritis, termed undifferentiated arthritis, with normal radiographic results. This early presentation has been encouraged with the recognition that great benefits to the patient exist if treatment is commenced early. The 1987 criteria were recognized as being relatively insensitive to the diagnosis of early disease and, as a result, revised criteria were drawn up in 2010 that notably did not include radiographic erosions in the scoring system [3]. This reflects the observation that erosions represent a late stage in the disease process. One of the earliest detectable changes in patients with rheumatoid arthritis is proliferation of the synovium the rheumatoid pannus. Both ultrasound and MRI are sensitive for the detection of synovitis, and both are superior to radiography. This article will address the increasing use of both ultrasound and MRI in the diagnosis and monitoring of rheumatoid arthritis and will highlight both the strengths and weaknesses of these two imaging modalities, with particular reference to bone erosions and synovitis. AJR:197, September

2 Rowbotham and Grainger Clinical Presentation Patients most frequently present with pain and stiffness in one or multiple joints. The wrists, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints are the most commonly affected joints, but any synovial joint can be affected. Involvement is usually bilateral and symmetric, and women are more commonly affected than men. In the hands, characteristic deformities may be seen. Spinal involvement is also common, and the atlantoaxial junction is an area frequently affected. In addition to joint-based pathology, patients may present with extraarticular manifestations of the disease, such as rheumatoid nodules, enthesopathy, bursitis, tenosynovitis, and tendon rupture. Rheumatoid factor (RF) is an immunoglobulin commonly found in patients with rheumatoid arthritis and is usually routinely measured in patients presenting with symptoms and signs of rheumatoid disease. It is not, however, specific to rheumatoid arthritis and may be elevated in other autoimmune disorders. Some patients with rheumatoid arthritis may remain negative for RF throughout the course of their condition, and these patients are described as having seronegative rheumatoid arthritis. Classification criteria have been devised for diagnosing rheumatoid arthritis to differentiate patients with this condition from those with undifferentiated inflammatory synovitis. Along with clinical criteria blood tests including RF, anticitrullinated protein antibodies and acute phase response measures erythrocyte sedimentation rate and C-reactive protein tests will usually be performed to aid and confirm the diagnosis [3]. Ultrasound Versus MRI Ultrasound and MRI both have advantages and disadvantages that should be taken into consideration when deciding which modality to use in any particular patient. Ultrasound allows the operator to make a clinical assessment of the patient at the time of imaging along with easily allowing examination of the contralateral side or additional joints. Ultrasound is more readily available in many centers and has fewer financial constraints relative to MRI. However, among the potential difficulties with ultrasound assessment of the joints are the inability to compare temporal changes directly at the time of scanning, nonvisualization of internal bone structure, inability to assess bone edema, and inherent operator dependence of the technique. Ultrasound can also be time consuming and has a long learning curve for the inexperienced operator. MRI has the advantage of providing a more global view of the joint, including the articular surfaces and internal bone structure. The disadvantages of using MRI include motion artifact, the increased time necessary for the examination, and potentially invasive administration of a contrast agent. MRI is also of relatively low resolution compared with ultrasound, and because contrast administration is required to reliably distinguish synovium from effusion the imaging of multiple joints can be difficult. Contraindications to MRI also remain a problem in some patients, and in these cases ultrasound and radiography will be required. Fig. 2 T1-weighted gadolinium-enhanced axial image through level of metacarpophalangeal (MCP) joints shows florid synovitis at fourth MCP joint (arrow) in 48-yearold woman. There is also tenosynovitis of middle finger flexor digitorum tendon seen as high signal within tendon sheath (arrowhead). Fig. 1 Rheumatoid arthritis affecting hip in 65-yearold woman. Sagittal T1-weighted fat-suppressed MR image shows enhancing synovium within joint capsule (arrows). Large erosion is seen in posterior femoral head (arrowhead). Synovitis Proliferative synovitis is the earliest pathologic change seen in rheumatoid arthritis and is usually but not exclusively bilateral and symmetric. Both ultrasound and MRI can detect preerosive synovitis and each has merits and disadvantages. Both have been shown to be superior to clinical assessment in detecting the presence of synovitis [4]. Definitions for synovitis on imaging have been produced by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) initiative [5]. On MRI, the OMERACT definition of synovitis is a thickened area of synovial compartment that shows greater than normal enhancement on gadolinium-enhanced T1- weighted images [5] (Figs. 1 and 2). Although a number of sequences can usefully show the presence of synovitis, it is recognized that the reference standard involves the use of gadolinium-enhanced T1-weighted images. Although synovitis is often less bright on fluid-sensitive sequences compared with joint fluid, without contrast administration, joint fluid and proliferative synovitis cannot be easily differentiated. Quantitative measurements of synovial volume are possible using MRI, and several studies have been published indicating that the volume of synovium correlates with disease activity in a given joint. The volume of synovitis present has also been shown to reduce within only 2 weeks of commencing methotrexate in some patients [6]. There is emerging evidence to suggest that dynamic contrast-enhanced MRI (DCE-MRI) is a more sensitive marker of disease activity than volumetric measurement of synovium [7]. Currently DCE-MRI is predominantly a research-based technique involving assessment of the rate of contrast uptake by the synovium. The knee, wrist, and MCP joints have been most commonly studied with this technique, and results suggest DCE-MRI is predictive of future erosive change and progression [8, 9] and response to treatment [7 9]. Differentiation of synovium from the adjacent cartilage is readily achieved on MRI, 542 AJR:197, September 2011

3 Imaging Rheumatoid Arthritis A B Fig. 3 Wrist synovitis in rheumatoid arthritis shown on ultrasound in 36-year-old woman. A, Long axis (coronal) ultrasound image along radial aspect of wrist shows low-reflective synovitis (asterisk). Parts of scaphoid (S) and abductor pollicis longus tendon (arrowhead) are also seen. R = radial styloid. B, Power Doppler ultrasound image shows vascularity within synovitis. a distinction that can be difficult using ultrasound. Thus, MRI is often still considered the imaging reference standard for synovial imaging. A potential drawback is that MRI appearances of synovitis are sometimes seen in healthy volunteers. Currently, there is no proposed pathophysiologic explanation for this finding [10]. The OMERACT definition of synovitis using ultrasound is abnormal hypoechoic (relative to subdermal fat but sometimes isoechoic or hyperechoic) intraarticular tissue that is nondisplaceable and poorly compressible and that may exhibit Doppler signal [11] (Fig. 3). The nondisplaceable nature of synovitis on ultrasound is important because this characteristic distinguishes joint fluid from synovial thickening; however, these two entities frequently coexist within one joint. Volumetric measurements on ultrasound are much more difficult to perform and are much less reproducible than using MRI and are therefore not routinely performed at present. Power Doppler ultrasound has been shown to have improved sensitivity for synovial inflammation compared with color Doppler ultrasound and is preferred for this reason. Positive power Doppler signal on ultrasound has been shown to correlate well with clinical disease activity within a joint and can be used as a quantitative A Fig year-old man with rheumatoid arthritis. A, Coronal T1-weighted image of wrist shows extensive erosions in triquetrum (arrowhead) and ulna (arrow). Smaller erosions are also seen in scaphoid and hamate. B, STIR image in same position shows marrow edema, particularly associated with sites of erosion. Note also synovitis (arrowhead) seen as intermediate signal on T1- weighted and high signal tissue on STIR imaging. B AJR:197, September

4 Rowbotham and Grainger Fig. 5 Transverse image across dorsum of third metacarpal base in 59-year-old woman with rheumatoid arthritis. Prominent erosion is seen (arrow). Extensor tendon to middle finger is seen overlying erosion (asterisk). indication of synovial inflammation [12]. Ultrasound has the advantage of clinical correlation and dynamic assessment of the joints at the time of scanning and is increasingly being performed by rheumatology clinicians in the outpatient setting. However, there are pitfalls the operator should be aware of when imaging for synovitis. Movement and noise artifact can occur and may be interpreted as false-positive power Doppler signal and the probe must be used with care, applying only slight pressure to avoid compression of the vessels, which produces a false-negative power Doppler signal. A study comparing the use of ultrasound and MRI in the fingers of patients with rheumatoid arthritis has shown a high degree of correlation of both B-mode synovitis and power Doppler signal with MRI [13]. Several published studies document the high level of agreement between MRI-reported synovitis and pathologic findings [14 16]. For this reason, MRI has often been used as the reference standard in studies assessing the accuracy of ultrasound detection of synovitis. Backhaus et al. [17] reported that ultrasound was more sensitive than MRI in detecting synovitis in a series of 60 patients who underwent multimodality imaging of the finger joints. A more recent study again examining interphalangeal joints with both ultrasound and MRI as well as with conventional radiography and clinical examination showed good agreement between ultrasound and MRI in the detection of synovitis (86.5%) and concluded that ultrasound was a reliable and valid method of assessment of synovitis [18]. Fig. 7 Transverse ultrasound at level of third (3) and fourth (4) metacarpal bases in 33-year-old woman with rheumatoid arthritis. Extensor digitorum tendons (arrowheads) are seen surrounded by mixed echogenicity fluid and synovitis that distends tendon sheath and represents severe tenosynovitis. Fig. 6 Ultrasound image of rheumatoid nodule overlying dorsal surface of proximal ulna in forearm in 42-year-old woman. Extensor surface is in typical location. Nodule is seen as heterogeneous low-reflective elongated mass (arrowheads) with ulna (U) seen deep in relation to it. Erosions Erosions are a common finding in rheumatoid arthritis and have been shown to be present in up to 97% of patients with the condition. The presence of bone erosions at the time of diagnosis has been shown to be related to a poor long-term clinical outcome. The OMERACT definition of an erosion on MRI is a sharply marginated bone lesion with correct juxtaarticular location and typical signal characteristics that is visible in at least two planes with a cortical break seen in at least one plane [5] (Fig. 4). In addition to breach of the cortex, the erosion itself generally contains inflammatory tissue or fluid showing high signal on T2-weighted images. The inflammatory tissue or synovium within the erosion will usually enhance with IV gadolinium. The volume of erosions calculated on MRI has been shown to have a high correlation with the volume detected on CT. The OMERACT definition of an erosion seen on ultrasound imaging is an intraarticular discontinuity of the bone surface that is visible in two perpendicular planes [11] (Fig. 5). Studies have suggested that ultrasound detection of erosions in a bone phantom model is a valid and reliable method when the erosions are at least 1 mm deep and 1.5 mm wide [19]. One problem seen with ultrasound but not with MRI is that some parts of the joint may be relatively inaccessible, for example, examining the radial and ulnar aspects of the MCP joints. Another potential pitfall of ultrasound detection of erosions is the misinterpretation of normal anatomic variants as erosions. Depressions seen on the dorsal aspects of the metacarpal heads that may be interpreted as erosions to the unwary operator have been described in healthy volunteers. However, metacarpal head depressions will have regular margins and no discontinuity of the cortex. There is conflicting published evidence in terms of which imaging modality has the superior sensitivity in terms of detecting erosions. 544 AJR:197, September 2011

5 Imaging Rheumatoid Arthritis TABLE 1: Comparison of Modalities Ultrasound MRI Strengths Weaknesses Strengths Weaknesses Real-time and dynamic imaging Unable to image within bone Ability to image deep within the joint and bone (e.g., marrow edema) Contraindications (e.g., pacemaker) Immediately accessible Difficulties with temporal comparison More complete assessment of whole joint including all articular surfaces Allows operator to undertake clinical assessment Power Doppler imaging correlates well with disease activity Relatively easy to examine multiple body regions Conventional radiography can no longer be used as a reference standard because it has been shown to be less sensitive for detecting erosions than either ultrasound or MRI. Multiplanar CT is thought to be the most sensitive modality for detecting erosions owing to its superior resolution of bone structure and its ability to clearly delineate cortical bony margins [20] but is rarely used for the detection and monitoring of rheumatoid arthritis for a variety of reasons, including the substantial radiation dose that would accumulate over the patient s lifetime. Ultrasound has also been shown to have an increased sensitivity for early erosions compared with radiography [21]. However, its position relative to MRI remains largely undetermined. Although Hoving et al. [22] reported that MRI has significantly increased sensitivity compared with ultrasound for detection of erosions in the hand and wrist, there is also evidence to suggest that ultrasound is at least as good as MRI in detecting wrist and MCP joint erosions and may even be better for the MCP joint [23]. MRI has been reported by several authors as being superior to conventional radiography. McQueen et al. [24] described carpal erosions in 45% of patients on MRI 4 months after the onset of symptoms compared with only 15% showing erosions on radiography. However, one study using CT as the reference standard suggested that the sensitivity of both ultrasound and MRI for detecting bone erosions is relatively low. Dohn et al. [25] reported sensitivities of only 68% and 42% for MRI and ultrasound, respectively, although only 17 patients with rheumatoid arthritis were included in the study. Poor depth penetration for larger joints and difficulty accessing parts of some joints Specialist training not always available Proven correlation of synovitis and histopathology Quantitative measurement of synovium Time and patient tolerance Limited to one body region Ideally IV contrast administration needed for synovitis assessment Operator dependent Readily reproducible Potential for motion artifact Other Manifestations of Rheumatoid Arthritis Rheumatoid arthritis is a systemic disease and most patients will have extraarticular manifestations in addition to joint-based disease. Rheumatoid nodules are the most common extraarticular complication and are present in approximately 30% of patients and almost exclusively seen in those who are RF positive. They tend to present in the chronic phase of disease, particularly on extensor surfaces and will be readily detected by both ultrasound and MRI. Ultrasound imaging is perhaps a more practical way of imaging rheumatoid nodules, showing them to be well defined and hypoechoic with poor internal vascularity (Fig. 6). MRI has the advantage of showing bone edema that is associated with erosive progression and poor functional outcome [26]. The OMERACT description of bone marrow edema on MRI is a lesion within the trabecular bone that has ill-defined margins and signal intensity characteristics consistent with increased water content that may be seen alone or surrounding an erosion or some other bone abnormality [5] (Fig. 4B). Bone marrow edema is thought to be a marker of early inflammatory change as a result of cellular infiltrates into the marrow; its presence appears to correlate well with raised levels of acute-phase reactants (C-reactive protein and erythrocyte sedimentation rate) [24]. It is a potentially reversible phenomenon, which may make it a useful imaging marker for disease activity in the future, particularly given its ability to provide prognostic information relating to disease progression. Tenosynovitis is also a common complication of rheumatoid disease. It most commonly affects the hands and wrists and is seen on both ultrasound and MRI as fluid or synovitis within a tendon sheath (Fig. 7). The extensor carpi ulnaris tendon appears to be most commonly affected [27]. Thickened tenosynovium will show enhancement with IV contrast administration on MRI (Fig. 2). It has been suggested that ulestrasound may be more sensitive than MRI for tendon sheath effusions [22]. Tendon rupture is also a relatively common complication and may contribute to joint deformity and dysfunction. Any tendon may be affected, but the wrist and ankle are most commonly involved. Both ultrasound and MRI may be used to detect tendon rupture, providing useful information if surgical reconstruction is contemplated. Conclusion Rheumatoid arthritis is a potentially devastating condition affecting a large proportion of the population; treatment has significantly progressed in recent years and outcomes, particularly when disease is diagnosed and treated at an early stage, are now significantly improved. As techniques that detect early disease, both ultrasound and MRI will become increasingly important in the diagnosis and management of this condition. There are few published studies directly comparing the sensitivity and specificity of these two modalities, particularly where a valid reference standard has been used. Future studies with increased patient numbers will be necessary if one of these two modalities is to emerge as a clear winner as the imaging modality of choice. 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