Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 Contents lists available at SciVerse ScienceDirect Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh 7 How to interpret plain radiographs in clinical practice Dr Andrew K. Brown, MBChB, MRCP, FHEA, PhD a, b, * a Senior Lecturer in Medical Education & Rheumatology, Hull York Medical School, University of York, United Kingdom Consultant Rheumatologist, York Teaching Hospital, NHS Foundation Trust, York, United Kingdom b a b s t r a c t Keywords: X-ray Plain radiographs Conventional radiography Rheumatoid arthritis Osteoarthritis Ankylosing spondylitis Psoriatic arthropathy Gout Calcium pyrophosphate deposition In this article I will consider the basic principles of requesting, acquiring, interpreting and reporting plain radiographs of joints, including assessment of the distribution of joint abnormalities, and specific pathological changes that may occur in bone, cartilage and soft tissues. I will then move on to a more specific discussion of the major arthropathies and the role of radiographs in the diagnosis and assessment in each condition as well as reviewing the combined abnormalities that may be visible on radiographs and how these relate to underlying pathological processes. Ó 2013 Elsevier Ltd. All rights reserved. Introduction Conventional radiography (plain radiographs or X-rays) has been used by physicians to provide additional information in patients with musculoskeletal symptoms for over a century. Despite advances in other imaging technologies such as ultrasonography (US), magnetic resonance imaging (MRI), computed tomography (CT) and nuclear scintigraphy, including single photon emission computed tomography (SPECT) and positron emission tomography (PET), plain radiographs remain an important and widely used first-line investigation by health professionals in primary and secondary care. This chapter will discuss the application of plain radiographs in the investigation and management of patients with arthritis. * Medical Education & Rheumatology, Hull York Medical School, University of York, York YO10 5DD, United Kingdom. Tel.: þ44 1094 726308. E-mail address: andrew.brown@hyms.ac.uk. 1521-6942/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.berh.2013.03.004 250 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 Advantages and disadvantages of plain radiography It is worth first considering some of the potential advantages and disadvantages of conventional radiography. One of the main advantages is that it is probably the most readily available and least expensive imaging modality. This means that a wide range of health professionals are able to readily access these data and almost all local patient populations are within a short distance of being able to have an X-ray performed. All medical professionals have received at least some basic training in X-ray interpretation and so this immediate access to information can generally be used by the requesting physician to aid diagnosis and management in a time efficient fashion. A wide range of pathological changes in bones, joints and cartilage can be evaluated with conventional radiography. However, it is also important to consider that many soft tissue structures, including the synovium, are not well visualised with plain radiographs and so X-rays cannot necessarily be relied upon to provide the most sensitive information for diagnostic or therapeutic decision making in patients with inflammatory arthritis. Other modalities such as US or MRI have a number of advantages in this context. In addition, it is important to recognise that a radiograph effectively provides a two-dimensional picture obtained from one slice through a three-dimensional structure. Therefore, the plane of assessment is crucial in order to provide as much information as possible, as there may be a danger of missing abnormalities if they are not caught in the path of the X-ray beam. For example, it is for this reason that plain radiography may provide less sensitive information compared with topographical techniques in the assessment of bone erosions in rheumatoid arthritis (RA). Performing and receiving a radiographic assessment is a well-regulated process and it is generally considered safe, although it does involve ionising radiation and the amount of radiation exposure varies dependent on the structure being visualised. For example an X-ray of the pelvis involves considerably more radiation exposure than an examination of a single limb joint, and the number of views and images obtained are proportional to the amount of radiation received. Data are generally regarded as reproducible as there are widely recognised standards for the acquisition of images and increasingly there are also validated conventions and scoring systems for interpreting and reporting various pathological processes, all of which are aimed at improving the reliability and reproducibility of radiographic acquisition and interpretation. This is important as radiographs are often used for repeated serial evaluation and follow-up, for example, in the assessment of progression of joint damage in RA. However, local variations remain relatively common. Basic principles of requesting plain radiographs of joints Which structures? Before requesting the test, it is important to consider the capabilities of radiographs, that is, what structures and pathology may be visualised using this modality and whether an alternative imaging technique may provide more useful information. For example, radiographs can be used to evaluate changes in joint and cartilage surfaces, bone pathology, joint space narrowing, fracture, subluxation and dislocation. However, soft tissue structures such as tendons, ligaments and synovium are not well visualised and alternative imaging may provide more sensitive and specific information. Often X-rays are performed as a standard baseline imaging investigation but discussion with a musculoskeletal radiologist may help to select the most appropriate subsequent test if additional information is still required. Correlation with clinical findings and information from other investigation and imaging results is always important and radiographs should not be interpreted in isolation. Which joints? In most cases, the choice of site of radiograph will be strongly influenced by a prior clinical assessment, and an X-ray requested of the patient’s symptomatic joint or joints. Exceptions to this may include a patient with RA where X-rays of both hands and feet may be used to evaluate extent of disease or structural damage which may be repeated serially over time, or a skeletal survey in an A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 251 oncology setting, looking for evidence of sub-clinical malignant disease, such as myeloma. Nevertheless, a fundamental principle of requesting any imaging investigation is that any findings need to be interpreted in clinical context, and it is therefore imperative that any X-ray request is accompanied by comprehensive clinical information. Which views? Consideration should also be applied as to which views or plains are requested of the joint. Usually it is appropriate to obtain two views at 90 apart, typically in antero-posterior (AP) and lateral or oblique plains. This is particularly important in the setting of trauma but may be less crucial in the assessment of arthropathy. There are a number of established techniques and protocols which have been developed to provide optimal imaging of most joints and for particular indications. However, it is important to remember that these only represent a two-dimensional ‘slice’ through a joint and so are likely to be less sensitive than a three-dimensional or topographical assessment. In addition, specialist views have been developed for particular indications. For example, a ‘ball-catchers’ view can be helpful to visualise more of the cartilage surfaces in the finger joints and a ‘skyline view’ may be useful for more accurate assessment of the patella-femoral joint. Compare sides and review previous radiographs It can often be helpful to compare findings in a symptomatic joint with those in a contralateral asymptomatic joint. For example in a patient with osteoarthritis (OA), an AP X-ray of the pelvis allows some comparison between both hip joints or in a patient with RA, an X-ray of both hands allows comparison between finger, hand and wrist joints. If there is an old X-ray of the area of interest, reviewing and comparing these images can also help to improve diagnostic certainty and evaluate any progression over time. Patient position The position of the patient can also be important. For example, requesting weight-bearing views can be much more informative in evaluating cartilage loss in the knees of a patient with OA or in providing additional information concerning biomechanical changes in the feet. Correlation with clinical and other imaging findings This is an important principle, as mentioned earlier. Any radiographic findings need to be interpreted in clinical context. Additionally further imaging may be required to provide more specific information. Discussion with a radiologist can often be helpful and a regular musculoskeletal radiology meeting can be a useful forum for specialist clinicians and radiologists to formally discuss and review more challenging cases. Important safety considerations It is important to remember that performing a plain radiograph exposes a patient to ionising radiation. This is particularly important in women of child-bearing age. Radiographs of deeper structures, such as the lumbar spine or pelvis, subject the patient to greater exposure than more superficial structures. It is important to be able to justify any radiation exposure on the basis of potential risk and benefit. The Department of Health Policy [1], (IR (ME)R 2000) covers this aspect in detail (www.dh.gov/ health/2012ionising-radiation-ragulations/). Basic principles of examining and reporting plain radiographs of joints Most clinicians will have a straightforward strategy for reviewing and interpreting skeletal X-rays, and this section aims to reprise some basic principles supplemented with the author’s experience and present some ideas that may help further develop a systematic approach. 252 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 Clearly a knowledge and understanding of anatomy and pathological effects on bone, cartilage, joints and soft tissues is crucial. Also it is important to be able to describe any obvious abnormality using simple descriptive language, words and phrases, for example, name the bone and describe the location and site of any abnormality, for example, right or left; proximal, middle or distal; head, neck or shaft and cortex or medulla. One should start by making sure that the radiographic and patient demographic data correspond and the correct image is being viewed. Is it the correct date; is it the right or left side of the body; has the region of interest been included and is positioning optimal and is there more than one view to assess? It may be that there is an obvious abnormality visible on the radiograph, in which case I would probably move straight on to describing and interpreting this. If not (and it is probably good practice to still do this, in case there is an additional, perhaps less obvious abnormality present), a coordinated systematic approach of formally looking at specific structures can be useful. This mental checklist should ensure that the likelihood of missing any abnormalities is reduced. 1. Consider bony alignment – are there any changes that may suggest fracture or dislocation? 2. Consider bone cortices – follow the outline of each bone as any breach in the cortex may indicate a fracture or arthropathy. 3. Consider bone texture – normally one expects to see a trabecular pattern within the substance of bones but any distortion of this may indicate pathology. 4. Joint space – a careful look at the joint space may demonstrate changes such as joint space narrowing due to cartilage loss or calcification of the cartilage (chondrocalcinosis), or new bone formation, for example, osteophytes. 5. Soft tissues – changes in the soft tissue densities adjacent to a joint may indicate a joint effusion. It is important to also review adjacent non-musculoskeletal structures looking for any pathological changes. Remember to look at all views, compare both sides and adjacent joints, review any previous images, consider clinical findings and correlate with other imaging and test results. Ask for a second opinion if any uncertainty, particularly a musculoskeletal radiologist, or consider presenting the case at a multidisciplinary radiology conference. A summary of the important factors to consider when interpreting a musculoskeletal radiograph is provided in Table 1. Radiographic abnormalities in bone, cartilage and soft tissues In each of the major arthropathies, different pathological processes can cause changes to bone, cartilage and soft tissue structures which may be demonstrable on radiographs. Whilst some of these pathological changes may be specific, one should recognise an overlap across different types of arthritis. In bone, changes include osteopenia, erosion, osteophyte and new bone formation, subchondral sclerosis and cyst development. There may be cartilage loss and calcification (chondrocalcinosis). Soft tissue swelling, calcification and deformity may be visible. Many of these changes may be in evidence on radiographs of affected joints in the different forms of arthritis (Table 2). Table 1 How to interpret a musculoskeletal radiograph – checklist. Check patient demographic details Is the image quality satisfactory? Are viewing angles optimal? Describe the obvious abnormality using simple descriptive language e.g. name the bone and describe the location and site of any abnormality Use a systematic approach - start with the bones (alignment, cortices, texture) then joints, cartilage, soft tissues Look at all views Compare both sides / adjacent joints / previous images Consider clinical findings Correlate with other imaging Ask for a second opinion – discuss case and clinical context with a specialist musculoskeletal radiologist A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 253 Table 2 Radiographic pathology in bone, cartilage and soft tissues in each major arthropathy. RA OA PsA AS Gout CPPD Bone Periarticular osteopenia Erosions adjacent to the joint New bone proliferation Erosion Periostitis Osteolysis New bone formation Erosion Erosion away from the joint Cartilage Joint space loss (usually uniform) Subchondral cysts Subchondral sclerosis Osteophytes Joint space loss (usually asymmetric) Subchondral cysts Subchondral sclerosis Osteophytes Chondrocalcinosis Joint space loss Soft tissue Soft tissue swelling Joint Ankylosis Deformity Bony remodelling Deformity Enthesitis Dactylitis Enthesitis Ankylosis Deformity Ankylosis Deformity Preserved unless severe Soft tissue swelling Tophi Deformity Calcification Soft tissue swelling RA – rheumatoid arthritis; OA – osteoarthritis; PsA – psoriatric arthritis; AS – ankylosing spondylitis; CPPD – calcium pyrophosphate crystal deposition. Assessment of distribution of joint abnormalities When assessing a patient with arthropathy, it is often useful to consider not only which joints are affected but also the pattern of distribution of joint involvement (Table 3). This can provide helpful information not only in the initial stages of diagnosis but also when thinking about prioritising which joints to assess during subsequent follow-up. These typical distributions of joint abnormalities are also Table 3 The typical distribution joint involvement in the more common types of arthritis. Type of arthropathy Distribution of pathology Rheumatoid arthritis Typically an inflammatory polyarthritis affecting the small joints of the hands, feet and wrists in a symmetrical distribution. A mono, oligo or polyarthritis typically affecting DIP and PIP joints, first CMC joint, axial skeleton and large weight bearing joints e.g. hips and knees. Usually one of five sub-types: 1. predominant DIP joint involvement; 2. asymmetrical mono or oligoarthritis usually involving the knee and small peripheral joints; 3. symmetrical peripheral polyarthritis resembling RA; 4. axial spondyloarthropathy/spondylitis; 5. arthritis mutilans associated with destruction, osteolysis and telescoping of the fingers. Usually involves the axial skeleton (sacroiliac joints and spine) (axial spondylitis). May have asymmetrical involvement of medium and large joints particularly shoulders and hips (peripheral spondylitis). Inflammation at sites of bone insertion of tendons and ligaments is common (enthesitis) e.g. iliac crests, gluteal and tibial tuborosities and heels. Typically asymmetrical mono or oligoarthritis of weight bearing lower limb joints, but other joints may be involved and may present as a polyarthritis. Usually a monoarthritis, most commonly first MTP joint, then mid-foot, ankle and knee; lower limb > upper limb. Usually a monoarthritis, most commonly knee then wrist, shoulder, ankle and elbow joints. Usually an oligoarthritis, most commonly knee then wrist, shoulder, elbow, hip, midtarsal and MCP joints. Osteoarthritis Psoriatic arthritis Ankylosing spondylitis Reactive arthritis Gout Acute calcium pyrophosphate arthritis “pseudogout” OA with CPPD (previously often called chronic pyrophosphate arthropathy) Septic arthritis Usually a monoarthritis most commonly affecting lower limb large/medium joints e.g. knee or less commonly hip although upper limb joints may be affected. May occasionally present as a polyarthritis if immunocompromised or underlying arthropathy such as RA. DIP – distal interphalangeal; PIP – proximal interphalangeal; CMC – carpometacarpal; MCP – metacarpophalangeal; MTP – metatarsophalangeal; CPPD – calcium pyrophosphate crystal deposition; OA – osteoarthritis; RA – rheumatoid arthritis. 254 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 important to take into account when choosing which joints to evaluate with plain radiographs and also when interpreting these images. Combined radiographic abnormalities that may occur with each major arthropathy Rheumatoid arthritis Plain radiography remains the gold standard for the assessment of structural joint damage in RA even though this may not necessarily be the most sensitive imaging investigation in this setting. Nevertheless, radiographs remain very important in the evaluation of these patients and have been historically used as a primary outcome measure in RA. Indeed, much of the evidence we commonly apply in the diagnosis and management of our RA patients continues to be based on longitudinal radiographic information [7]. When a patient with inflammatory arthritis is initially assessed in the rheumatology outpatient clinic, as well as a clinical, biochemical and immunological investigations, it is usual to perform plain radiographs of the hands and feet. This is supported by most national rheumatology guidelines [8]. Even if symptoms are predominantly in the hands, it is important not to neglect the feet and perform a radiographic assessment of the hands, wrists and feet, and any other affected joints at the physician’s discretion, as erosive changes may be present in the feet and not the hands in early disease [9]. This may improve the diagnostic utility of radiographs in the baseline evaluation of patients with early disease. Large joint radiographs of RA patients have been less frequently studied; however, studies including large joints of patients with established disease indicate good correlation between radiographic erosions of large and small joints [10]. This information can be useful to not only help establish a diagnosis but also determine the extent of disease and help ascertain risk of progression and prognosis. For example, the presence of radiographic erosions often confers more severe disease and worse prognosis [2] and a number of studies have demonstrated a correlation between joint damage seen on radiographs and disability in long-standing RA, although this link is perhaps less strong in patients with early disease [3]. It is important to note that X-rays are often normal at onset and during the early stages of the condition and the more characteristic radiographic features may only develop in more established disease. Studies have estimated that less than half of new RA patients attending their first rheumatology clinic visit may have visible radiographic erosions and in the remainder of patients X-rays are often normal [12,13]. Moreover, a third of new RA patients may not develop radiographic erosions within the first 2 years of disease onset [11]. It is therefore important to also evaluate other nonradiographic markers of disease severity when planning individual patient management. This has led to some authors questioning the utility of radiographs in the assessment of early RA, as bony changes visible on X-ray often lag behind clinically detectable joint and soft tissue inflammation. In addition, studies comparing radiographs with other imaging techniques such as US, MRI and CT have all confirmed the reduced sensitivity of X-rays at detecting early erosive changes [14–16]. Other studies suggest that the majority of patients will have developed some radiographic changes within 2 years of diagnosis [17,18] and most national recommendations support the value of a baseline radiographic assessment although caution should be applied when interpreting the significance of normal X-rays in this situation. Radiographs may therefore perhaps be more usefully applied in the serial assessment of joints affected by RA, looking for evidence of progression of joint damage over time. Nevertheless, most specialists would suggest that radiographs of hands and feet should be performed at baseline and every 6–12 months in early RA and perhaps every 1–2 years in more established disease. This is reflected in recent modifications to the RA classification criteria. Previous criteria, which included radiographic changes [4], were mainly applied to clinical and epidemiological research studies but have only been shown to be sensitive and specific for the diagnosis of active, established RA. Their sensitivity may be low in early RA, particularly <12 weeks duration [5], as the classical features of RA such as radiographic erosions and rheumatoid nodules, which are included in these criteria, are often absent at disease onset. In response to this, a collaborative initiative undertaken by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) was launched A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 255 Fig. 1. Early rheumatoid arthritis. Bone erosions are visible in the left index finger MCP joint and left middle finger PIP joint. which has resulted in the publication of the 2010 Rheumatoid Arthritis Classification [6], which focusses on features at an earlier stage of disease, rather than defining the disease by late stage features, and does not include radiographic changes. A range of pathological abnormalities may be visualised radiographically in RA. These include soft tissue swelling, periarticular (juxta-articular) osteopenia, erosions, joint space narrowing (usually uniform) and deformity such as subluxation and dislocation (Figs. 1 and 2). It is important to remember that radiographs only provide limited information on soft tissue structures and US or MRI are the Fig. 2. Severe established rheumatoid arthritis. There is advanced destructive arthropathy with erosive disease predominantly affecting the MCP and wrist joints bilaterally. This is most marked on the right with marked MCP joint damage, subluxation and deformity with ulnar deviation. Joint space and cartilage loss is demonstrated throughout. There has been severe destruction and ankylosis of the carpal bones bilaterally. There is pronounced osteopenia throughout. 256 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 imaging modalities of choice to directly visualise these structures and provide important objective information on pathological changes such as synovitis and tenosynovitis. For this purpose, radiographic assessment relies on the interpretation of soft tissue shadows corresponding to, for example, elevation of the fat pad in the elbow joint or suprapatellar pouch of the knee, which may suggest a joint effusion or synovitis, and is therefore not necessarily sensitive or specific for assessing inflammation. These pathological abnormalities can be observed in a range of joints with the distribution largely correlating with the established clinical pattern of a symmetrical peripheral joint polyarthritis, characteristic of RA. As such it is usually the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in the fingers, metatarsophalangeal (MTP) joints in the forefeet and all compartments of the wrists that are most commonly involved. In addition, joints in the midfoot and hindfoot, knees, glenohumeral joint at the shoulder, the elbow and cervical spine can also be affected. The most common first radiographic sign is often periarticular osteopenia as bone density is reduced adjacent to the joint as a result of local synovial inflammation. The bone may appear less dense (a darker shade on the radiograph) around the articular surfaces, although this is not necessarily a specific radiographic sign of RA and can occur in other conditions. When synovial inflammation is not controlled, through either delayed diagnosis or lack of response to therapy, then cartilage and bone destruction can occur. The inflamed synovium slowly invades adjacent structures causing damage and destruction to the cartilage and bone leading to joint space narrowing and bone erosion that can be seen on radiographs (Fig. 1). The joint space narrowing in RA tends to be uniform and concentric reflecting the generalised nature of the synovial inflammation within the joint, whereas in other conditions such as OA, it may be more uneven and asymmetric. The erosions in RA tend to be periarticular and are often described as marginal erosions as they are close to the joint and reflect the site of pathology. The most likely sites to visualise early erosive changes in RA include the radial aspects of the second and third MCP joints in the hand, the ulnar styloid at the wrist and the lateral aspect of the fifth MTP joint. If the disease remains untreated, progression inevitably occurs resulting in more extensive erosive joint damage and destruction within the joint. There may also be progressive distension of the joint capsule that increases joint instability, which causes biomechanical compromise and may also accelerate joint damage. These factors contribute to the development of joint subluxation and ankylosis and characteristic deformities such as ulnar deviation and subluxation resulting in boutonnière and swan neck deformities of the finger joints (Fig. 2). It is always important to consider the cervical spine as part of a radiographic assessment in patients with RA. In cases of established RA, up to 80% of patients may develop changes in this region, usually at the atlanto-axial joint as a result of progressive erosion and bone damage reflecting ongoing, uncontrolled inflammation and pannus formation. In extreme cases, this joint can become subluxed in either an anterior, lateral or vertical direction with potentially serious consequences of spinal cord or brainstem compression. Radiographs can be used to assess the alignment of this region using AP and lateral views with comparison of images with the neck held in a forward flexion and neutral or extended position (Fig. 3). If the anterior atlanto-dental interval (AADI) is >3 mm, then atlanto-axial subluxation should be suspected and further imaging usually in the form of an MRI scan should be performed for more accurate evaluation of inflammation and erosive damage and comprehensive assessment of bony, soft tissue and neurological structures [19]. Progression of structural damage to joints is commonly used as an outcome measure in RA. This is most commonly measured by applying scoring systems to assess radiographs of the hands, wrists and feet. Several validated scoring systems have been developed for radiographic evaluation of RA pathological features. The best known of these are the Sharp and Larson scores. They tend to be rather complex and involve summating scores for erosions and joint space narrowing in the hands, wrists and feet, perhaps limiting their utility in routine clinical practice, but they are nevertheless important in research studies, particularly as an outcome measure for measuring the efficacy of therapies and assessing longitudinal response to treatment. Extensive research has confirmed both their validity and reliability amongst appropriately trained practitioners for the measurement of disease severity and particularly progression of bone and joint destruction over time [20]. The radiographic initial score at the time of diagnosis has been shown to be a reliable predictor of future radiographic structural damage [21]. A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 257 Fig. 3. Atlanto-axial subluxation in rheumatoid arthritis. Anterior atlanto-axial subluxation is present on neck flexion as the anterior atlanto-dental interval (AADI) (arrow) measures 10 mm. Note erosive changes in the odontoid peg. AADI is measured from the postero-inferior margin of the anterior arch of the atlas to the anterior surface of the odontoid; greater than 3 mm is considered abnormal; 3–6 mm indicates early instability; greater than 9 mm is regarded by some authors as an indication for surgical stabilisation although should be correlated with clinical and MRI findings [19]. In summary, baseline radiographs may be useful in some patients to identify features of RA such as periarticular osteopenia, joint space narrowing or erosions. Repeated radiographic assessment is an established measure of disease progression, patient outcome and response to treatment. In addition, consideration should be given to radiographic assessment of other joints particularly the atlanto-axial region of the cervical spine in patients with established and particularly severe RA, to assess for evidence of bone damage and subluxation. Osteoarthritis Plain radiographs remain the standard investigation in the assessment and diagnosis of OA. In the clinical setting, imaging is usually targeted to the symptomatic joint but often other joints can be affected by OA but not necessarily the symptomatic joint. The opposite situation may also be true, meaning that clinical correlation is always important. The typical distribution involves the large lower limb weight-bearing joints of the knee and hip, further up the kinetic chain in the lumbar and cervical spine, and peripheral joints including the thumb bases (especially dominant hand), proximal and distal interphalangeal joints of the fingers and first metatarsophalangeal joints in the feet. Any joint articular surface that has been subject to previous trauma or fracture may be at risk of developing premature OA. Radiographs can be used to inform a diagnosis of OA, determine disease severity, in monitoring, for example, post joint replacement, and to evaluate structural progression. However, sensitivity and specificity may be less for detecting early changes of OA. In addition, the optimal frequency of repeat radiographs to inform clinical management is not well defined. As with other types of arthritis, due consideration is needed as to the plain of assessment (e.g., a ‘sky-line’ view to assess the patella-femoral joint in the knee), positioning (e.g., X-ray the hip joint in a standing position with 15–20 of internal rotation) and correlation with clinical and other imaging findings. Post X-ray processing techniques such as digital image analysis and magnification techniques 258 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 can help. Standardised and consistently applied image acquisition techniques are clearly important to ensure reliable and reproducible images particularly to allow meaningful comparison over time, for example, post joint replacement surveillance and in the assessment of structural progression. The radiographic hallmark of OA is loss of joint space reflecting degeneration and thinning of articular cartilage. Meniscal cartilage lesions and cartilage extrusion may also contribute. Joint space narrowing is more likely to be asymmetrical reflecting localised cartilage damage rather than the more usual symmetrical appearances in inflammatory arthropathies such as RA. Weight-bearing X-rays may be useful to more accurately assess the degree of joint space narrowing, particularly in joints such as the knee and hip, to ensure that the articular surfaces are in direct contact at the time the X-ray picture is taken. The subchondral bone can be affected by excess load-bearing forces leading to cyst formation. In response to cartilage loss, a pathophysiological repair process occurs with new bone formation producing osteophytes at the joint margin, and thickening and sclerosis of the subchondral bone, visible as increased ‘whitening’ on the radiograph (Fig. 4). Eventually collapse, subluxation and bone remodelling may occur (Fig. 5) although ankylosis is uncommon. Abnormal alignment may result, for example, varus or valgus deformities affecting the knee. Erosions may be seen but unlike RA or gout these are usually centrally located within the joint, characteristically in the distal interphalangeal joints of the fingers where they have been described as a ‘seagull wing’ appearance (‘erosive’ OA). Particularly in the early phase of the disease, inflammation may contribute perhaps provoked by products of cartilage damage, causing soft tissue swelling which may be visible on the radiograph. It should be noted that other arthropathies may co-exist, particularly calcium pyrophosphate crystal deposition (CPPD), producing additional radiographic features including chondrocalcinosis, and that OA can be a secondary reaction to cartilage damage produced by inflammatory joint disease such as RA. Demineralisation (osteopenia) is usually absent and would be much more in keeping with an inflammatory arthropathy such as RA. A number of scoring systems have been developed in order to attempt to provide more objective measures as to the severity of OA. Probably one of the oldest and most well-known, but still widely used, systems is the Kellgran and Lawrence system. This may be used to classify the severity of OA according to a five-point scale: Grade 0: Normal. Grade I: Doubtful: that is, possible narrowing of the joint space and osteophytes. Fig. 4. Osteoarthritis of the hands. Joint space loss, subchondral cysts and osteophytes are present particularly at the left first CMC joint. Similar changes with the addition of subchondral sclerosis are also present in a number of DIP and PIP joints with subluxation and deformity of the right index finger DIP joint. A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 259 Fig. 5. Osteoarthritis of the hips. Advanced osteoarthritis is present in the left hip with marked joint space loss, sclerosis, osteophyte formation with remodelling and superior migration of the femoral head. Significant osteoarthritis is also present in the right hip with joint space loss, subchondral cysts and osteophytes. Note new bone formation around entheseal attachments at the greater trochanters and around the pelvis. Grade II: Minimal: that is, small osteophytes, mild narrowing of the joint space. Grade III: Moderate: that is, multiple, moderately sized osteophytes, definite joint space narrowing, some sclerotic areas and possible deformity of bone contour. Grade IV: Severe: that is, multiple large osteophytes, severe joint space narrowing, marked sclerosis and definite deformity of bone contour. Adapted from Ref. [36] In daily clinical practice a semi-quantitative scale is often employed describing pathological changes, particularly joint space narrowing, as minimal, moderate or severe. Quantitative measurement of joint space width, usually in millimetres, is often used in research studies to evaluate OA structural progression and effects of therapy on structure modification and remains the optimal recognised technique for this purpose. This is applied most commonly in the knee and also has been used in the hip and hand joints. However, it can be a challenging outcome measure with which to demonstrate any change over time and may not be a reliable surrogate for cartilage loss and subject to other confounding variables [37]. Psoriatic arthritis Plain radiographs are also an important imaging modality in the assessment of patients with psoriatic arthropathy (PsA) although the greater range of differing manifestations of this disease means that varying radiographic patterns of joint and soft tissue involvement can be observed. A range of pathological abnormalities may be visualised radiographically in PsA. Similar to RA, these may include soft tissue swelling, joint space narrowing and erosions but differentiating features include in particular proliferative new bone formation as well as periostitis, ankylosis and osteolysis. These pathological abnormalities can be observed in a range of synovial joints with changes also affecting the axial skeleton and fibrocartilaginous joints such as the sacroiliac joints and entheseal attachments of tendons and ligaments. The distribution can be much more variable with up to five recognised patterns including predominant distal interphalangeal joint involvement; asymmetrical mono- or oligoarthritis usually involving the knee and small peripheral joints; a symmetrical peripheral polyarthritis resembling RA; an axial spondyloarthropathy or spondylitis and finally arthritis mutilans associated with destruction, osteolysis and telescoping of the fingers. Up to a quarter of patients with PsA may have sacroiliitis and changes may be more extensive and are more likely to be asymmetrical in PsA and reactive arthritis than in ankylosing spondylitis (AS) [22]. Spondylitis is also relatively common and often indistinguishable from AS, although in PsA 260 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 syndesmophytes may be less extensive and are less likely to form consecutive bridging between adjacent vertebrae. Typical patterns of joint involvement in the hand include inflammatory changes in the distal and proximal interphalangeal joints or a combination of diffuse soft tissue swelling, and tenosynovitis and synovitis characteristic of dactylitis, which can also affect the toes (‘sausage-digits’) [23]. Changes in the feet often involve the MTP and interphalangeal joints, particularly the interphalangeal joints of the great toe. Phalangeal tufts can also be affected. Not uncommonly the distribution of affected joints can mimic RA with symmetrical synovial swelling of the small joints of the hands, feet and wrists which can damage and destroy joints in a similar fashion to RA [24]. Indeed, it has been suggested that PsA may be a more disabling and erosive condition than previously recognised [25]. The feet are commonly affected in PsA. An inflammatory oligoarthritis can also occur with the involvement of small and/or large joints in particular involving the ankles, knees and shoulders. Like in RA, the expression of radiographic changes in early disease is often inconsistent and it is not until the disease is established that the more characteristic radiographic changes may be seen. Up to half of patients with early PsA may have evidence of radiographic bone damage within 2 years of presentation [26]. However, there is characteristically a combination of bone destruction and new bone formation. Erosions may be seen which can be indistinguishable from those seen in early RA in that they are characteristically well defined and situated in a peri-articular location but are more likely to be asymmetric. However, in contrast to RA, these changes are usually associated with proliferative new bone formation which can give the erosion a speculated appearance particularly towards its margins (Fig. 6). Other changes that can be seen may include soft tissue swelling due to dactylitis, periostitis which can affect the bony shaft and spondylitis. If the disease does not respond to treatment and progress, the bone destruction may worsen meaning the erosions become more irregular and indistinct whilst new bone formation continues. This can result in some characteristic deformities including ‘pencil-in-cup’ changes affecting the distal interphalangeal joints with the middle phalanx taking on a pointed tip appearance through progressive erosion and osteolysis, whereas the base of the distal phalanx expands and curves laterally as new bone is formed (Fig. 7). Further bony proliferative change can occur as a result of ongoing entheseal inflammation. These can be visible on radiographs and most commonly occur in sites such as the achilles tendon and plantar fascia insertion sites at the calcaneum as well as at sites of tendinous and ligamentous attachments around the pelvis. Like the other major arthropathies, scoring methods have been developed in an attempt to quantify changes more objectively. Examples include the modified Steinbrocker score, Ratingen method for PsA, Sharp score (similar to RA) and van der Heijde modification of the Sharp method [32]. Fig. 6. Psoriatic arthropathy of the fingers. Early changes of psoriatic arthropathy affecting the interphalangeal joints of both thumbs and DIP joints of all the fingers in the right hand and the left middle finger. There is evidence of joint space loss, erosions and new bone formation. A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 261 Fig. 7. Psoriatic arthropathy of the toes. More advanced changes are present in the feet with advance erosive changes present particular at the right great to PIP joint where there has been marked osteolysis and early “pencil and cup” deformity. Ankylosing spondylitis AS almost universally affects the sacro-iliac joints as well as the axial skeleton. Bone erosion, new bone formation, ankylosis and enthesitis are common pathological features all of which may be visualised on radiographs. Radiographs remain an important tool in informing the diagnosis of AS. Usually the first radiographic changes of AS can be found in the sacroiliac joints as symmetrical sacroiliitis (Fig. 8), and such findings have a high specificity for this condition. However, although up to 95% of AS patients may Fig. 8. Ankylosing spondylitis associated sacroiliitis. Early sacroiliitis is demonstrated on this radiograph of the pelvis with loss of clarity and sclerosis in the lower third of the sacroiliac joints, particularly affecting the iliac side of the right sacroiliac joint. Hip joint appearances are normal. 262 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 develop radiographic changes, they may take up to 9 years to appear as X-rays are only able to detect more chronic bony changes [33]. The first radiographic finding of sacroiliitis is usually seen in the synovial portion of the joint which comprises the anterior and inferior one-half to two-thirds (the remainder of the joint is ligamentous). Typically appearances are bilateral and symmetrical. The iliac aspect of this region is usually the best place to look, as the articular cartilage tends to be thinner here. One should look for erosions at this site although early changes can be rather subtle. Focus on the margins of the joint and look for loss of clarity and definition of the white line of the bone cortex which can progress to give the appearance of a widened joint space. Bony proliferation then tends to occur as part of the body’s repair response producing sclerosis and increased whitening of the bone on the radiograph. As the disease process progresses, the joint can eventually fuse or ankylose (Fig. 9) and as such lose its ability to move, which can alter the load bearing and create more mechanical stresses in the adjacent structures. The ligaments holding together the posterior portion of the joint can also calcify, contributing to the sclerotic radiographic appearances of this region, often obscuring the joint itself and making interpretation more challenging. The sensitivity of radiography to detect these changes can be improved by using a specific angulated viewing position, such as the modified Ferguson view, whereby the patient lies on their back with knees and hips flexed and the X-ray tube is centred at the L5-S1 level and then angled 25–30 towards the head. One should usually not rely on a standard AP X-ray of the pelvis as the optimal method of visualising the sacroiliac joints. However, a pelvic radiograph may be beneficial to evaluate other areas which may be affected in cases of spondyloarthropathy such as the hips and pubic symphysis, looking for erosions and new bone formation, as well as ligament and tendon attachment around the pelvis, looking for changes of enthesopathy. The diagnosis of AS is usually made by applying criteria that combine clinical and radiographic findings. Amongst the most commonly used is the New York Criteria which requires demonstration of either bilateral sacroiliitis at least grade 2 (minimal sacroiliitis: loss of definition of the joint margins, minimal sclerosis, joint space narrowing and erosions) or unilateral sacroiliitis at least grade 3 (moderate sacroiliitis: definite sclerosis on both sides of the joint, erosions and loss of joint space) [31]. However, these changes may occur a few years after the development of characteristic symptoms of inflammatory back pain so their diagnostic utility may not be optimal for early disease. This probably relates to a number of factors including the difficulty in optimally imaging such an obliquely angled joint with its twisting articular surfaces and complex anatomy, relatively poor inter- and intra-rater reliability in image interpretation and the fact that radiographs are only able to detect established bony changes in these joints and not active inflammation [30]. This relatively poor sensitivity has led to recent modifications to the classification criteria for axial spondyloarthropathy which now allow Fig. 9. Advanced ankylosing spondylitis. Advanced AS with ankylosis or fusion of the sacroiliac joints. A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 263 identification of sacroillitis by MRI [27]. MRI can identify both inflammation and bone erosions of the sacroiliac joints and is more sensitive than conventional radiography in the detection of sacroiliitis and may detect changes despite normal X-rays [29]. Some studies have estimated that the additional rate of detection with contrast-enhanced MRI may be as much as 75% [28]. Precise MRI sequencing can help, and in particular using fat suppression techniques such as STIR sequences can improve detection of bone marrow oedema which correlates well with active inflammation. As such MRI may be a more useful imaging tool in detecting early axial spondyloarthropathy. Besides the sacroiliac joints, similar pathological changes of AS may be seen in the cervical, thoracic and lumbar spine. Radiographs may demonstrate erosions, new bone proliferation, ligamentous ossification as well as squaring and fusion of the vertebral bones. The first changes usually appear at the thoracolumbar junction with small erosions and adjacent new bone formation at the corners of the vertebral bodies. This produces a ‘shiny corner’ appearance which is called a Romanus lesion. Bony proliferation usually dominates leading to further new bone formation along the anterior aspect of the vertebral body which may cause loss of the normal concave contour giving the vertebral body a squared-off appearance. As the condition progresses, ossification and calcification can begin to affect the outer fibres of the annulus fibrosis of the intervertebral disk and the longitudinal spinal ligaments forming syndesmophytes. These specific lesions can further develop to form vertical bony spurs which may eventually form a bridge between adjacent vertebrae leading to a so-called ‘bamboo spine’ appearance, which is characteristic of severely established AS (Fig. 10). The facet joints can be similarly affected. New bone formation and ossification of other soft tissue structures can also occur, particularly the posterior interspinous ligament which in severe cases can be visualised as a solid radio-opaque white band in the midline. Similar to the sacro-iliac joints, ongoing inflammation can eventually result in portions of the spine becoming ankylosed resulting in loss of mobility and functional impairment and disability. As a result of altered biomechanics and load bearing, Fig. 10. Advanced ankylosing spondylitis. Advanced AS with bridging ostophytes affecting the thoracic and lumbar spine. 264 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 fractures may occur through an ankylosed disk or vertebral body creating a pseudo-arthrosis, often referred to as an Andersson lesion. These more chronic radiographic changes in the spine are not part of current diagnostic criteria for AS because the presence of spinal changes in association with radiographically normal sacroiliac joints is unusual. The current ASAS recommendations suggest that X-rays of the cervical and lumbar spine should be performed. Their utility is probably greatest in helping to determine extent of disease and also for following longitudinal progression. Lateral views are usually the most sensitive ones and involve less radiation exposure. ASAS recommendations suggest that although changes in the thoracic spine can be seen relatively frequently, interpretation can be more challenging due to additional shadows projected from overlying soft tissue and organ structures [34]. The frequency of repeat radiographs to assess structural progression is uncertain but most authors seem to suggest no less than every 2 years, given the usual slow rate of progression of these bony changes in AS. A number of validated scoring systems have been developed for assessment of radiographic changes of AS in the spine and include the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) which assesses 24 sites on the lateral cervical and lumbar spine for sclerosis, squaring or erosion; syndesmophytes and bony bridge formation. Other methods also exist and include the Bath Ankylosing Spondylitis Radiological Index (BASRI) which also includes the sacroiliac joints and the Stoke Ankylosing Spondylitis Spinal Score (SASSS). Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) has selected the mSASSS as the preferred method of scoring structural damage in AS, as this system is supported by data confirming good reproducibility and sensitivity to change [35]. As discussed above, diagnostic and classification criteria have evolved over time and authors often now refer to this spectrum of diseases as spondyloarthritis, subdivided into axial spondyloarthritis (with AS being the prototype disease) and peripheral spondyloarthritis [34]. Certainly, involvement of joints and entheses of the peripheral skeleton is relatively common. The distribution of joint involvement is more commonly asymmetrical, affecting medium and large joints particularly hips, shoulders and knees as well as metatarsophalangeal joints. Pathological changes may be detected radiographically. The hips are most frequently involved and changes are usually bilateral and symmetrical and the presence of hip disease may be a poor prognostic sign. Typically there is uniform narrowing of the joint space (reflecting synovial inflammation) and osteophyte formation at the junction of the femoral head and neck often forming a ‘collared’ appearance. With ongoing joint damage the femoral head may migrate upwards or there may be intra-pelvic displacement of the medial acetabular wall, referred to as ‘acetabular protrusio’. A third of patients may experience shoulder involvement and again features tend to be bilateral and symmetrical. Typical radiographic features include joint space narrowing, erosions, bony proliferation of ligament attachments and the possibility of ultimately ankylosis. Inflammation at sites insertion of tendons and ligaments into bone (enthesitis) is common are more difficult to demonstrate with radiographs until the point of new bone and enthesophyte formation. Such changes may be seen in sites such as the iliac crests, gluteal and tibial tuborosities and typical bony spurs at the achilles tendon and plantar fascia insertions in the calcaneum may also be detected. Other imaging techniques such as US and MRI may be more sensitive at detecting these entheseal changes at an earlier stage. Crystal arthropathy These are a range of arthropathies characterised by crystal deposition within joints and periarticular tissues. The most common types are gout and calcium pyrophosphate disease. The radiographic findings in both of these related conditions will be considered. i. Gout Gout is an inflammatory arthropathy associated with deposition of monosodium urate crystals in joints, resulting from chronic elevation of tissue urate levels. It is a common condition, especially in middle-aged and older men and is often associated with modifiable risk factors, for example, obesity, excessive beer or spirit intake, hypertension, diuretic use and renal impairment. The diagnosis is A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 265 usually made clinically and is confirmed by demonstration of monosodium urate crystals (negatively birefringent needles) on compensated polarised light microscopy of synovial fluid. Identification of crystals is fundamental for making the correct diagnosis and excluding other causes such as sepsis. Radiographs can be helpful in more chronic cases. A typical initial presentation is an acute, severe, self-limiting inflammatory monoarthritis involving the great toe metatarsophalangeal joint (podagra). It can also present as a monoarthrits in other joints, oligoarthritis, polyarthritis or chemical cellulitis. Chronic recurrence is common, associated with tophi formation and joint damage. Radiographs can be used as part of the diagnostic process (although not included in the diagnostic criteria) and to monitor progression. Radiographic changes are usually monoarticular and asymmetrical and are usually a legacy of recurrent disease. In acute gout, radiographs may be normal although soft tissue swelling may be visible. In cases of chronic gout (recurrent acute episodes over time) a variety of radiographic features may be visible. Often the earliest changes are bone erosions as recurrent inflammation causes damage to the bony surfaces. The classic erosion appearance is of a punched-out lesion with sclerotic margins and overhanging edges which is commonly located in the para-articular area but may be located some distance away from the joint (note different site and appearance to a rheumatoid erosion and the absence of periarticular osteoporosis and, unless severe, maintenance of the joint space). However, recurrent attacks of acute inflammation may result in progressive bony destruction with loss of joint space, erosive progression and deformity (Fig. 11). It is also important to look at the soft tissues as soft tissue densities or calcified opacities may be apparent caused by recurrent uric acid crystal deposition and formation of tophi. ii. Calcium pyrophosphate crystal deposition CPPD is characterised by deposition of calcium pyrophosphate crystals predominantly in articular hyaline and fibrocartilage (chondrocalcinosis). There are familial and sporadic forms and the condition may be associated with underlying metabolic disease. It is a common cause of acute inflammatory monoarthritis in the elderly. It has a variety of clinical manifestations: Fig. 11. Gout. This is advanced gouty arthropathy with marked erosive bone destruction and resultant deformity. Note the characteristic appearance and site of the erosion in the head of the first metatarsal bone when a slightly rotated plain is used. Tophi are visible in the soft tissues between the first and second metatarsal bones. 266 A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 asymptomatic incidental finding of chondrocalcinosis; associated with acute inflammatory mono- or oligoarthritis (acute CPP crystal arthritis – ‘pseudogout’) and chronic arthritis – OA plus CPPD (previously termed chronic pyrophosphate arthropathy). Like gout, the diagnosis is usually made clinically and is confirmed by demonstration of characteristic crystals (non-birefringent or weakly positively birefringent rods or rhomboids) on compensated polarised light microscopy of synovial fluid. Typical distribution of joint involvement includes large and medium-sized joints, commonly knees and also wrists, shoulders, ankles, elbows and others. Plain radiographs are useful to demonstrate calcification and can sometimes aid diagnosis. This can affect a variety of sites. Chondrocalcinosis is characteristic and can involve both fibrocartilage, for example, knee menisci, wrist triangular fibrocartilage and symphysis pubis, and hyaline cartilage, for example, knee, gleno-humeral joint and hip (Fig. 12). Calcification may also occur in the joint capsule and synovium, for example, in the MCP and knee joints. There may also be calcification of soft tissue structures particularly the entheses of achilles, triceps, obturator tendons and bursae in subacromial, olecranon and retrocalcaneal sites. It should be remembered that chondrocalcinosis is a relatively frequent finding in otherwise healthy people. In fact it may be present in up to a third of those aged 65– 75 with increasing incidence in older populations, the majority of whom are usually asymptomatic. Chondrocalcinosis is also associated with other metabolic conditions including hyperparathyroidism, haemochromatosis, hypophosphatasia and hypomagnesaemia. In more chronic cases, structural changes may develop. These often resemble OA with cartilage loss, sclerosis, cysts and osteophytes (Fig. 13). Features more specific to CPPD include more prominent ‘exuberant’ osteophytes and large subchondral cysts particularly at the knee and wrist joints which contribute to the so-called ‘hypertrophic’ appearance characteristic of this condition. The involvement of other joints less typically affected by OA, for example, MCP, gleno-humoral, ankle, mid-foot and radiocarpal (often associated with scaphoid-lunate dissociation), can also provide useful clues to this diagnosis. Smooth ‘pressure’ erosions may occur, for example, at the anterior distal femur, distal inferior radioulna joint and radio-carpal joint. The relatively rare variant of destructive pyrophosphate arthropathy may cause marked cartilage and bone loss over a fairly short period of time, often resulting in changes Fig. 12. Calcium pyrophosphate arthropathy associated chondrocalcinosis. There is chondrocalcinosis demonstrated within the medial and lateral compartments of the left knee joint but relative preservation of joint spaces. A.K. Brown / Best Practice & Research Clinical Rheumatology 27 (2013) 249–269 267 Fig. 13. Calcium pyrophosphate arthropathy. Chondrocalcinosis is present in the triangular fibrocartilage in the ulna-carpal regions of both wrists, particularly the right. There is joint space loss at the right index finger MCP joint. Marked subchondral sclerosis, cysts, joint space loss and osteophytes are present at both first CMC joints. resembling a Charcot joint. Occasionally CPPD deposition may occur in soft tissue structures such as tendons (calcific tendonitis) and bursae and be associated with the development of subcutaneous nodules. Summary Despite ongoing advances in imaging techniques and technologies, radiography continues to be a key investigation in the initial assessment, diagnosis and ongoing management of patients with arthropathy. 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Abbreviations AADI: anterior atlanto-dental interval ACR: American College of Rheumatology AP: antero-posterior AS: ankylosing spondylitis ASAS: Assessment of SpondyloArthritis international Society BASRI: Bath Ankylosing Spondylitis Radiological Index CMC: carpometacarpal CPPD: calcium pyrophosphate crystal deposition CT: computed tomography EULAR: European League Against Rheumatism NICE: National Institute of Clinical Excellence MCP: metacarpophalangeal MTP: metatarsophalangeal MRI: magnetic resonance imaging mSASSS: Modified Stoke Ankylosing Spondylitis Spinal Score OA: osteoarthritis OMERACT: Outcome Measures In Rheumatoid Arthritis Clinical Trials PET: positron emission tomography PIP: proximal interphalangeal PsA: psoriatic arthritis RA: rheumatoid arthritis SASSS: Stoke Ankylosing Spondylitis Spinal Score SPECT: single photon emission computed tomography STIR: short tau inversion recovery US: ultrasonography
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