The diverse clinical states and sites of pathology in gout provide challenges when considering the features apparent on imaging. Ideally, an imaging modality should capture all aspects of disease including monosodium urate crystal deposition, acute inflammation, tophus, tissue remodelling and complications of disease. The modalities used in gout include conventional radiography, ultrasonography, magnetic resonance imaging, computed tomography and dual-energy computed tomography. This review discusses the role of each of these imaging modalities in gout, focussing on the imaging characteristics, role in gout diagnosis and role for disease monitoring. Ultrasonography and dual-energy computed tomography are particularly promising methods for both non-invasive diagnosis and monitoring of disease. The observation that ultrasonographic appearances of monosodium urate crystal deposition can be observed in patients with hyperuricaemia but no other clinical features of gout raises important questions about disease definitions.
Gout: disease states
The central feature of gout is deposition of monosodium urate (MSU) crystals. These crystals form in the context of elevated urate concentrations above saturation levels (>6.8 mg dl −1 at physiological temperature and pH) . MSU crystals frequently deposit within the joint, coating articular cartilage . These crystals may be observed in joints of patients with asymptomatic hyperuricaemia and in clinically uninvolved joints of patients with previous gout attacks . However, these crystals can induce an acute inflammatory response, leading to the clinical presentation of acute gouty arthritis, an exquisitely painful condition that typically resolves spontaneously over 10–14 days. In some patients, gouty tophi also develop within joints, periarticular structures or subcutaneous tissue. Tophi represent a chronic foreign-body granulomatous response to MSU crystals , and may invade bone, leading to development of bone erosion and tissue remodelling . In advanced disease, complications of disease include severe bone and joint damage, superimposed soft-tissue and bone infection and tendon rupture.
The diverse states and sites of disease provide challenges when considering the imaging appearances of gout. Ideally, an imaging modality should capture all aspects of disease including MSU crystal deposition, acute inflammation, tophus, tissue remodelling and complications of disease ( Table 1 ). The most commonly used imaging modalities for gout are conventional radiography (CR), ultrasonography (US), magnetic resonance imaging (MRI), computed tomography (CT) and dual-energy CT (DECT). Each modality has strengths and weaknesses in the assessment of gout ( Table 2 ). This review will discuss the role of each of these imaging modalities in gout, focussing on the imaging characteristics and role in gout diagnosis and in disease monitoring.
| MSU crystals | Bone erosion | Joint space narrowing | Tophus | Synovitis | Bone marrow oedema | Tendon disease | |
|---|---|---|---|---|---|---|---|
| Conventional radiography (CR) | – | + | + | +/− | – | – | – |
| Ultrasonography (US) | – | + | – | + | + | – | + |
| Magnetic resonance imaging (MRI) | – | + | + | + | + | + | + |
| Conventional computed tomography (CT) | – | + | + | + | – | – | + |
| Dual-energy computed tomography (DECT) | + | + | + | + | – | – | + |
| Imaging modality | Strengths | Weaknesses |
|---|---|---|
| Conventional radiography (CR) | Inexpensive Widely available High specificity for gout | Low sensitivity Less accurate than MRI or US for detection of erosions Characteristic features occur late in disease, when diagnosis is usually established Unable to detect many features of disease including MSU crystal deposition |
| Ultrasonography (US) | Increasing availability in clinic High specificity for gout diagnosis (double contour sign and tophus) Excellent inter-reader agreement for tophus Able to detect subcutaneous and deep tissue tophi | Operator dependent Low sensitivity Abnormalities may be evident in patients with asymptomatic hyperuricaemia (significance unknown) |
| Magnetic resonance imaging (MRI) | Able to detect subcutaneous and deep tissue tophi | Expensive Requires specialised equipment Patient acceptability Unable to directly visualise MSU crystal deposition |
| Conventional computed tomography (CT) | Able to detect subcutaneous and deep tissue tophi Short scanning time | Expensive Requires specialised equipment Use of ionising radiation Unable to directly visualise MSU crystal deposition |
| Dual-energy computed tomography (DECT) | Able to directly visualise MSU crystal deposition Excellent inter-reader agreement | Expensive Requires specialised equipment, not widely available Use of ionising radiation Sensitivity in early gout not established |
Conventional radiography (CR)
The basic conventional radiography (CR) technique of passing X-rays through a body part onto a flat detector and thus generating a projectional image has not changed substantially since Roentgen discovered it in 1895. The first description of the CR appearances of gout was in the 19th century, soon after discovery of CR . For almost a century, CR was the dominant method of gout imaging, and the typical CR characteristics of disease are well characterised. Recent decades have seen the introduction of digital detection systems rather than films and these are now standard across much of the world. Digital radiographs do provide improved dynamic range and thereby contrast definition, especially for soft tissues, compared with traditional film radiography .
Imaging characteristics
In patients with early disease, radiographs may be entirely normal, or show periarticular soft-tissue or joint effusion at the time of an acute flare . In advanced gout, tophi may be observed as asymmetrical, lobulated soft-tissue masses with or without calcification . The consequences of tophus deposition within or adjacent to articular structures may also be apparent using CR, including characteristic bone erosion ( Fig. 1 ). Erosions and other CR features of chronic gout may be present before clinically apparent subcutaneous tophi develop . In gout, bone erosion may be observed in both intra- and extra-articular sites, and are typically characterised by well defined borders, with sclerotic margins and overhanging edges. Typically, the erosions are located at or even beyond the margins of the articular cartilage and synovial attachments. Subchondral erosions are usually a later feature. In advanced tophaceous gout, erosions may coalesce, leading to the appearance of joint space widening, subchondral collapse, osteolysis and telescoping digits. In contrast to other erosive inflammatory arthropathies such as rheumatoid arthritis (RA), periarticular osteopaenia is not a major feature of gout. New bone formation including spurs, sclerosis, periosteal new bone formation and osteophytes may also be present, often in association with bone erosion . Joint space narrowing is a relatively late feature of gout, but does occur, particularly in the context of severe erosive disease. Ankylosis and subluxation are late features of advanced gout. Intraosseous calcification occurs in around 6% of patients with gout, usually in the hands and feet . Such calcification occurs within urate deposits that, in most cases, arise from the adjacent joint and penetrate through cartilage into the underlying trabecular bone .
The vast majority (86%) of patients with CR abnormalities of gout have abnormalities in the feet . As with the clinical presentation of gout, the 1st metatarsophalangeal joint (MTPJ) is most frequently affected on CR, , followed by the 5th MTPJ and midfoot. The hands and wrists are less frequently affected; hand and wrist abnormalities are present in approximately two-thirds of patients with CR features of gout.
CR can detect some complications of disease, including bone erosion and cartilage loss, as outlined above. Involvement of soft tissues is not well defined by CR, although the consequences of ligament disruption may be observed, for example scapholunate dissociation at the wrist . Inflammatory changes in synovium and bone and deposition of MSU crystals are not well observed using CR.
Role in gout diagnosis
Although CR does not allow direct observation of MSU crystals, this modality is included in the current (1977) American Rheumatology Association classification criteria for gout . The CR features included in these criteria are asymmetric swelling within a joint, and sub-cortical cysts without erosions. It should be noted that these features frequently occur in other rheumatic diseases. In a study of patients with suspected gout, CR features suggestive of gout (defined as soft-tissue opacifications with densities between soft-tissue and bone, articular and periarticular bone erosions and osteophytes at the margins of opacifications or erosions) were found to have a low sensitivity (31%) but high specificity (93%) for a clinical diagnosis of gout . The issue of diagnostic sensitivity is particularly relevant in patients with recent onset of disease, where acute gout attacks may be infrequent and CR is frequently normal. This issue has been highlighted in a study of the value of hand radiographs in patients with early arthritis that reported that hand radiographs were unable to predict gout .
Role in disease monitoring
A key advantage of CR is its feasibility; this modality is inexpensive, widely available and does not depend to a large extent on operator skill for acquisition of images. This makes CR a potentially useful modality for monitoring of disease, both for clinical practice and in clinical trials. The key features that can be serially monitored using CR are bone erosion and joint space narrowing. A quantitative scoring system has been established for monitoring of structural damage in gout, which is a modification of the Sharp-van der Heijde method for RA scoring . This method is reproducible, and has high face and construct validity. Scores are typically higher in patients with subcutaneous tophi and in those with longer disease duration. Bone erosion scores using this method correlate highly with CT erosion scores, noting that CT is usually considered the gold standard for imaging of bone erosion . Bone and joint damage scored using this method correlates highly with measures of musculoskeletal disability , and also with circulating markers of bone resorption, including osteoclast precursor levels and serum receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations in patients with gout . To date, structure modification (such as changes in erosion or joint space narrowing) using CR has not been reported in clinical trials of gout. A 10-year longitudinal study of 39 patients with gout did not demonstrate a relationship between serum urate lowering and radiographic changes, using a qualitative method of CR assessment . Thus, a key unresolved question is whether intensive urate lowering therapy (ULT) or other treatments can prevent radiographic damage progression or even lead to healing of erosions in chronic gout as assessed by CR.
Although the CR scoring method appears to have high construct and concurrent validity, this method may underestimate the extent of bone and joint damage due to gout. The issue of sensitivity has been highlighted by comparison of CR with other forms of imaging. This is of particular relevance when monitoring for complications of disease. Both US and MRI are able to detect bone erosions that are not clinically apparent using CR .
Conventional radiography (CR)
The basic conventional radiography (CR) technique of passing X-rays through a body part onto a flat detector and thus generating a projectional image has not changed substantially since Roentgen discovered it in 1895. The first description of the CR appearances of gout was in the 19th century, soon after discovery of CR . For almost a century, CR was the dominant method of gout imaging, and the typical CR characteristics of disease are well characterised. Recent decades have seen the introduction of digital detection systems rather than films and these are now standard across much of the world. Digital radiographs do provide improved dynamic range and thereby contrast definition, especially for soft tissues, compared with traditional film radiography .
Imaging characteristics
In patients with early disease, radiographs may be entirely normal, or show periarticular soft-tissue or joint effusion at the time of an acute flare . In advanced gout, tophi may be observed as asymmetrical, lobulated soft-tissue masses with or without calcification . The consequences of tophus deposition within or adjacent to articular structures may also be apparent using CR, including characteristic bone erosion ( Fig. 1 ). Erosions and other CR features of chronic gout may be present before clinically apparent subcutaneous tophi develop . In gout, bone erosion may be observed in both intra- and extra-articular sites, and are typically characterised by well defined borders, with sclerotic margins and overhanging edges. Typically, the erosions are located at or even beyond the margins of the articular cartilage and synovial attachments. Subchondral erosions are usually a later feature. In advanced tophaceous gout, erosions may coalesce, leading to the appearance of joint space widening, subchondral collapse, osteolysis and telescoping digits. In contrast to other erosive inflammatory arthropathies such as rheumatoid arthritis (RA), periarticular osteopaenia is not a major feature of gout. New bone formation including spurs, sclerosis, periosteal new bone formation and osteophytes may also be present, often in association with bone erosion . Joint space narrowing is a relatively late feature of gout, but does occur, particularly in the context of severe erosive disease. Ankylosis and subluxation are late features of advanced gout. Intraosseous calcification occurs in around 6% of patients with gout, usually in the hands and feet . Such calcification occurs within urate deposits that, in most cases, arise from the adjacent joint and penetrate through cartilage into the underlying trabecular bone .
The vast majority (86%) of patients with CR abnormalities of gout have abnormalities in the feet . As with the clinical presentation of gout, the 1st metatarsophalangeal joint (MTPJ) is most frequently affected on CR, , followed by the 5th MTPJ and midfoot. The hands and wrists are less frequently affected; hand and wrist abnormalities are present in approximately two-thirds of patients with CR features of gout.
CR can detect some complications of disease, including bone erosion and cartilage loss, as outlined above. Involvement of soft tissues is not well defined by CR, although the consequences of ligament disruption may be observed, for example scapholunate dissociation at the wrist . Inflammatory changes in synovium and bone and deposition of MSU crystals are not well observed using CR.
Role in gout diagnosis
Although CR does not allow direct observation of MSU crystals, this modality is included in the current (1977) American Rheumatology Association classification criteria for gout . The CR features included in these criteria are asymmetric swelling within a joint, and sub-cortical cysts without erosions. It should be noted that these features frequently occur in other rheumatic diseases. In a study of patients with suspected gout, CR features suggestive of gout (defined as soft-tissue opacifications with densities between soft-tissue and bone, articular and periarticular bone erosions and osteophytes at the margins of opacifications or erosions) were found to have a low sensitivity (31%) but high specificity (93%) for a clinical diagnosis of gout . The issue of diagnostic sensitivity is particularly relevant in patients with recent onset of disease, where acute gout attacks may be infrequent and CR is frequently normal. This issue has been highlighted in a study of the value of hand radiographs in patients with early arthritis that reported that hand radiographs were unable to predict gout .
Role in disease monitoring
A key advantage of CR is its feasibility; this modality is inexpensive, widely available and does not depend to a large extent on operator skill for acquisition of images. This makes CR a potentially useful modality for monitoring of disease, both for clinical practice and in clinical trials. The key features that can be serially monitored using CR are bone erosion and joint space narrowing. A quantitative scoring system has been established for monitoring of structural damage in gout, which is a modification of the Sharp-van der Heijde method for RA scoring . This method is reproducible, and has high face and construct validity. Scores are typically higher in patients with subcutaneous tophi and in those with longer disease duration. Bone erosion scores using this method correlate highly with CT erosion scores, noting that CT is usually considered the gold standard for imaging of bone erosion . Bone and joint damage scored using this method correlates highly with measures of musculoskeletal disability , and also with circulating markers of bone resorption, including osteoclast precursor levels and serum receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations in patients with gout . To date, structure modification (such as changes in erosion or joint space narrowing) using CR has not been reported in clinical trials of gout. A 10-year longitudinal study of 39 patients with gout did not demonstrate a relationship between serum urate lowering and radiographic changes, using a qualitative method of CR assessment . Thus, a key unresolved question is whether intensive urate lowering therapy (ULT) or other treatments can prevent radiographic damage progression or even lead to healing of erosions in chronic gout as assessed by CR.
Although the CR scoring method appears to have high construct and concurrent validity, this method may underestimate the extent of bone and joint damage due to gout. The issue of sensitivity has been highlighted by comparison of CR with other forms of imaging. This is of particular relevance when monitoring for complications of disease. Both US and MRI are able to detect bone erosions that are not clinically apparent using CR .
US
The increasing availability of US within the clinic makes this a useful clinical tool for both diagnosis and monitoring. This modality has the potential to assess many aspects of the disease, including MSU crystal deposition, acute inflammatory changes and synovial, bone and soft-tissue involvement. In addition to being reasonably inexpensive and widely available, US has the advantages of using harmless sound rather than ionising radiation and can be combined with clinical examination. It also has the ability to detect and quantify blood flow, such as within inflamed synovium. Its disadvantages include a complete inability to see within or through bone and a rapid drop-off of signal and detail with increasing depth. Fortunately, in gout, most relevant lesions are near the skin surface. US is also dependent on the skill of the operator, is hard to perform in a reproducible manner and may be very time consuming if more than one or two sites are examined.
Imaging characteristics
The ‘double contour’ sign has been defined as “a hyperechoic band over anechoic cartilage” and is thought to represent MSU crystal deposition on articular cartilage ( Fig. 2 A). The US appearance of cartilage affected by gout can be differentiated from calcium pyrophosphate crystal deposition, which typically appears as crystal deposition within articular cartilage and calcification of fibrocartilage . Features of acute gouty inflammation on US include joint effusion that may have a ‘snowstorm appearance’ due to free MSU crystals within synovial fluid , synovial hypertrophy and power Doppler (PD) signal consistent with hypervascularity . Hyperechoic spots in the synovium may also be observed . Features of chronic gout on US include bone erosion and tophus. The US appearance of tophus has been defined as “hypoechoic to hyperechoic, inhomogeneous material often surrounded by a small anechoic rim” ( Fig. 2 B). Tophi may be observed within joints, soft-tissue structures such as tendons, ligaments and bursae, and also invading into bone .
Role in gout diagnosis
US has several potential roles in gout diagnosis. The first role is to guide aspiration of synovial fluid for the gold standard of gout diagnosis: that is, microscopic identification of MSU crystals. This technique may assist with identification of joint effusions and selection of sites for aspiration. In addition, some US features are considered highly specific for gout, and may allow a diagnosis of gout in the absence of microscopically proven disease. This issue has been examined in a number of US studies, summarised in Table 3 . In these studies, the double contour sign has high specificity (≥0.95) for gout (either crystal proven or using clinical criteria), compared with other arthritis controls or disease free controls. However, the sensitivity for gout is lower, ranging from 0.22 to 0.92 in the studies reported to date. It should also be noted that the vast majority of studies reported have involved world experts in musculoskeletal US. Most studies have reported excellent concordance between observers in the ability to detect the double contour sign when assessing acquired images , but it remains to be seen whether such high degrees of accuracy can be maintained by those without such expertise when assessing US scans in real time.
| Sign | Gout diagnosis | Control population | Site of assessment | Sensitivity | Specificity | Reference |
|---|---|---|---|---|---|---|
| Double contour sign | Crystal proven ( n = 23) | Arthritis controls ( n = 23) | Affected joints (MTP1 predominated) | 0.92 a | 1.0 | |
| Double contour sign | Clinical diagnosis ( n = 28) or crystal proven ( n = 11) | Arthritis controls ( n = 14) and disease free controls ( n = 8) | MTP1s | 0.22 | 1.0 | |
| Double contour sign | Crystal proven ( n = 53) | Arthritis controls ( n = 50) | MTPs Knees MCPS | 0.67 0.57 0.21 | 0.98 1.0 1.0 | |
| Double contour sign | Clinical diagnosis ( n = 32) | Arthritis controls ( n = 48 with CPPD and n = 52 with other arthritis) | Knees | 0.44 | 0.99 | |
| Double contour sign or tophus | Clinical diagnosis ( n = 14) | Disease free controls ( n = 19) | Knees and MTP1s | 0.50 | 0.95 | |
| Tophus | Crystal proven ( n = 23 patients, n = 23 MTP1) | Arthritis controls ( n = 23 patients, n = 11 MTP1) | MTP1s | 1.0 | 1.0 | |
| Tophus b | Clinical diagnosis ( n = 28) or crystal proven ( n = 11) | Arthritis controls ( n = 14) and disease free controls ( n = 8) | MTP1s | 0.35 | 0.91 | |
| Tophus | Crystal proven ( n = 53) | Arthritis controls ( n = 50) | MTPs Knees MCPS | 0.74 0.42 0.23 | 1.0 1.0 1.0 | |
| Hyperechoic soft-tissue area | Clinical diagnosis or crystal proven ( n = 55) | Arthritis controls ( n = 31) | Affected joints (MTP1 predominated) | 0.79 a | 0.95 a |
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