Advanced Imaging in Gout

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1 Musculoskeletal Imaging Review Girish et al. Imaging of Gout Musculoskeletal Imaging Review Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved FOCUS ON: Gandikota Girish 1 Katrina N. Glazebrook 2 Jon. Jacobson 1 Girish G, Glazebrook KN, Jacobson J Keywords: academic research faculty, dual-energy low-kilovoltage CT, gout, hospital, MRI, musculoskeletal imaging, musculoskeletal system appendicular DOI: /JR Received February 14, 2013; accepted after revision pril 8, Department of Radiology, University of Michigan Hospitals, 1500 E Medical Center Dr, TC 2910, nn rbor, MI ddress correspondence to G. Girish (ggirish@umich.edu). 2 Department of Radiology, Mayo Clinic, Rochester, MN. JR 2013; 201: X/13/ merican Roentgen Ray Society dvanced Imaging in Gout OJECTIVE. The purpose of this article is to describe the role of advanced imaging using ultrasound, CT, and MRI in the assessment and diagnosis of gout. CONCLUSION. Dual-energy CT can quantitatively identify monosodium urate crystal deposits with high sensitivity and specificity within joints, tendons, and periarticular soft tissues. There are several characteristic ultrasound imaging findings, which include visualization of echogenic monosodium urate crystal deposition, tophus, and adjacent erosions. MRI is sensitive in showing soft-tissue and osseous abnormalities of gout, although the imaging findings are not specific. Gout commonly involves specific joints and anatomic structures, and knowledge of these sites and imaging appearances are clues to the correct diagnosis. cute gouty arthritis of the first metatarsophalangeal joint, termed podagra, was first identified by Egyptians in 2640.C. and continues to be a medical health problem today [1]. The hallmark of gout is hyperuricemia with subsequent deposition of monosodium urate (MSU) crystals, which leads to inflammation and symptoms. Improved understanding of the pathophysiology of gout and significant advances in imaging technology in the last decade has led to multiple noninvasive imaging techniques for the diagnosis of gout. The management of gout and its associated morbidities are expected to be transformed with the expanded role of ultrasound and dual-energy CT (DECT). t ultrasound, the combination of joint effusion, tophus, erosion, and the double contour sign is said to be diagnostic of gout in 97% of cases [2]. DECT has been used to reveal the distribution and quantity of deposited MSU crystals in gout. lthough further research is required, it may be possible to obviate joint aspiration for diagnosis in certain cases on the basis of the presence of imaging findings, thereby affecting treatment decisions [3]. MRI is another imaging method that may be used in the evaluation of gout [4]. The purpose of this article is to review recent advances in imaging of gout and its clinical applications. Epidemiology Gout is the most common inflammatory arthritis affecting men in the developed world and is also the most common crystalline arthropathy [5 7]. The prevalence of gout in the United States doubled between the 1960s and 1990s and continues to increase along with increasing obesity and hypertension in the general population [8, 9]. Zhu et al. [10] reported the prevalence of gout diagnosed by health professionals to be 3.9% among United States adults according to the National Health and Nutrition Examination Survey ; the prevalence of hyperuricemia was much greater (21.4%). Cause and ssociations The symptoms of gout are due to the body s reaction to the deposited MSU crystals. Supersaturation and deposition of MSU crystals in the joints and soft tissues are linked to high serum uric acid concentrations. Diet, genetics, and possibly weather play a role in this process. Research implicates the role of excessive dietary purines (present in meat and alcohol) in gout [11]. The intake of animal-based purines and fats that release fatty acids in the circulation have also been implicated [11, 12]. Most (about 80%) patients with gout also have a positive family history or hyperuricemia [13]. The highest incidence of gouty attacks is reported in the spring [14, 15]. JR:201, September

2 Girish et al. Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved The presence of deposited MSU crystals does not always lead to clinical symptoms or signs of inflammation and may also be seen in asymptomatic hyperuricemia. The activation of the inflammatory pathway by MSU crystals is the subject of current research. Gouty inflammation appears to be primarily interleukin-1 mediated [16]. MSU crystals trigger interleukin-1β production in macrophages by activating the NLP3 inflammasome pathway [17 19]. With a better understanding of the pathophysiology of gout, the advent of new biologic agents and improved dose regimen of known therapeutic drugs provide more effective options for the treatment of gout and control of acute gout symptoms [20]. Patients with gout have significant morbidity (specifically pain), and gout has a strong association with metabolic syndrome [8], myocardial infarction [21 23], diabetes mellitus [24], and premature death [22, 25]. Reduction in morbidity in gout can be brought about by early definitive diagnosis and effective management. ssessment of treatment response will be an integral part of effective management. Imaging has the potential to play an important supportive role in definitive diagnosis and assessment of treatment response. Diagnosis Traditionally, and even to this day, gout is largely diagnosed clinically, often by nonspecialists. Identification of MSU crystals in the joint aspirate is considered the reference standard in the diagnosis of gout but may not be identifiable in up to 25% of acute gout cases [26]. Ideally, aspirate should be sent for analysis of crystals, as well as WC count and culture to exclude infection. MSU crystals are thin and needle-shaped and have negative birefringence on polarized microscopy. Formalin should not be used in the transporting medium because the MSU crystals dissolve in formalin, creating false-negative results. For some clinicians, especially nonspecialists, aspiration and analysis may not be a practical or feasible option in their clinical practice. Hyperuricemia, which is considered to have a strong association with gout, may not be present in up to 42% of patients with acute gout attacks [27]. typical presentations of gout mimicking other disease processes are being more frequently encountered. Given these diagnostic challenges, gout is often suboptimally managed [20, 28]. Recent advances in diagnostic imaging of gout, specifically in the field of ultrasound and DECT, have a great potential in helping clinicians with more accurate assessment and diagnosis of gout. Radiography Radiography has historically been used to confirm suspected gout; however, classic findings seen on radiography, such as marginal erosions with overhanging edges and sclerotic margins, occur late in the disease process. Softtissue nodules (tophi) are also a feature of longstanding gout. The use of high-frequency ultrasound, DECT, and MRI can reveal findings supportive of gout, even early in the disease process, thus potentially securing a definitive role in early diagnosis and management of gout. Ultrasound High-frequency transducers (12 MHz and higher) provide high-resolution imaging that is well-suited for the evaluation of gout. The increased use of ultrasound machines in clinics and outpatient centers and by the bedside is related to the portability of ultrasound machines and their relatively decreased cost compared with larger more conventional cart-based ultrasound units. Unlike CT, ultrasound uses no ionizing radiation and, unlike MRI, it is relatively less expensive. Color Doppler imaging in ultrasound can assess vascularity without the use of contrast agents. The use of 3D ultrasound may have a future role in the evaluation of gout, which allows multiplanar imaging and reconstruction, analogous to volume imaging in CT or MRI [29]. Ultrasound is, however, very operator dependent and does have a long learning curve. Ultrasound examination of an extremity such as the foot can be accomplished in a relatively short time (< 15 minutes) with an approach that targets the most common site of involvement (the medial distal first metatarsal) and any symptomatic site when the sonographer is familiar with the sonographic features of gout. Ultrasound Findings: Joint Ultrasound findings in gout include joint effusion, synovitis, and erosions. MSU crystals are known to deposit in the joint, over the hyaline cartilage, and within the capsular soft tissues. Ultrasound is more sensitive than clinical examination in detecting joint effusion in gout [30, 31]. The characteristic hyperechoic floating aggregates of MSU crystals (microtophi) can sometimes be seen in the joint, described as a snowstorm appearance [32] (Fig. 1). However, the ultrasound appearances may be nonspecific. Rettenbacher et al. [32] and de Miguel et al. [33] found these hyperechoic foci to be very specific for gout and asymptomatic hyperuricemia, whereas Wright et al. [34] found that hyperechoic foci were also seen in healthy control subjects in equal numbers when compared with patients with gout. The ultrasound appearance of MSU crystal deposition on hyaline cartilage is characteristic. The deposits are found on the most superficial layer of the hyaline articular cartilage and appear as an irregular hyperechoic line over the anechoic cartilage. This hyperechoic line together with another underlying hyperechoic line caused by subchondral bone give the appearance of a double contour sign [2] (Fig. 2). lthough this is a specific sign for the diagnosis of gout and asymptomatic hyperuricemia, it is not very sensitive. Filippucci et al. [35] estimated its sensitivity and specificity to be 43.7% and 99%, respectively. ccording to other studies, the sensitivity of this finding in patients with gout ranges from 25% to 95% [34 38]. Interreader reliability of diagnosing this sign is also reported to be excellent [35, 36, 39]. This sign can disappear with successful urate-lowering therapy, and ultrasound can document this change [40]. Care should be taken not to misinterpret the normal cartilage interface sign as the double contour sign of gout. The cartilage interface sign, in which the surface of the hyaline cartilage is more reflective when associated with overlying fluid, depends on the angle of insonation, disappears where the cartilage curves away from the horizontal plane, and is not perpendicular to the sound beam. The double contour sign should also be differentiated from hyperechoic foci within the substance of the cartilage, seen with calcium pyrophosphate deposition [41]. Synovitis in gout tends to be heterogeneous but predominantly hyperechoic (Fig. 3) because of MSU deposits. Synovitis may also show intrinsic hypoechoic streaks and a hypoechoic peripheral rim with increased vascularity that likely corresponds to inflammatory areas [32]. Synovitis can also be nodular and masslike. On the other hand, synovitis in rheumatoid arthritis is commonly hypoechoic and less concentric, with more fingerlike extensions, and often shows an arborizing pattern [42]. The reflective echoes of MSU deposits and characteristic involvement of the first metatarsal are other helpful features to further differentiate gout from other inflammatory diseases. Erosions are seen in long-standing gout, usually next to tophi (Fig. 4). Tophi can acti- 516 JR:201, September 2013

3 Imaging of Gout Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved vate osteoclasts and have inhibitory effect on osteoblasts in the adjacent bone, thereby resulting in bone loss [43]. The Outcome Measures in Rheumatology group, an international informal organized network formed to improve outcome measurements in rheumatology, defines an erosion on ultrasound as an intraarticular discontinuity of the bone surface that is seen in two perpendicular planes [44]. Care should be taken not to misinterpret normal variations, cortical irregularity resulting from degenerative and traumatic change, and osteophyte as erosions. Correlation with radiography is helpful to exclude underlying degenerative and traumatic changes. Importance given to cortical discontinuity, irregular margins, and depth and width of discontinuity raises the specificity for diagnosing erosions. ctive erosions can be suspected in the presence of adjacent tophi or synovitis and hyperemia on color Doppler imaging (Figs. 1 and 4). The characteristic overhanging edge of an erosion resulting from gout, when present, is a very useful finding in providing an ultrasound diagnosis (see Fig. 4). Ultrasound Findings: ursa and Subcutaneous Tissues Ultrasound is able to clearly depict tophaceous deposits in bursa, tendons, ligaments, and soft tissues. tophus is a feature of longstanding gout and is the result of the body s inflammatory response to deposited MSU crystals [45]. Tophaceous deposits appear hyperechoic, with an anechoic rim, and can have a nodular or infiltrative appearance [36, 42]. The term tophus has been loosely used in the ultrasound literature, with no clear distinction drawn from intraarticular synovial hypertrophy [11, 46]. gouty tophus may show posterior acoustic shadowing due to sound-beam attenuation and possible calcification. The presence of calcification associated with a tophus may suggest concomitant disturbance in calcium metabolism [13]. With appropriate and effective treatment, primarily involving urate-lowering drugs, a tophus may reduce in size and completely resolve [47]. The olecranon bursa is a site that is commonly involved with gout [13]. Deposition of MSU crystals may also involve tendons. de Ávila Fernandes et al. [48] examined 138 different areas of tendon involvement with gout and found that MSU deposits most commonly enveloped the tendon (45%). small proportion of the patients had primarily intratendinous deposits. Knowledge of preferred tendon involvement can also be helpful in the diagnosis of gout. The chilles and peroneal tendons are common sites of involvement in the foot [49] (Fig. 5). The popliteus tendon (Fig. 6) and intercondylar groove involving the cruciate ligaments are common intraarticular locations in the knee [50]. The patellar tendon and infrapatellar fat pad are preferred sites in the extensor region of the knee. CT CT allows excellent 2D and 3D representation of the bone and soft tissues. Tophi are seen as discrete masses with a density of HU, which is higher than that of adjacent soft tissues. Tophi can be seen within the bone, about joints, within tendons, and in the soft tissues. CT also defines the well-demarcated corticated erosions with overhanging margin at intraarticular and extraarticular sites, which are often associated with tophi (Fig. 7). Dalbeth et al. [51] studied paired radiographs and CT scans in 798 individual hand and wrist joints in 20 patients. Where an erosion was present, 82% of joints showed adjacent tophi, and this proportion increased to 100% for larger erosions (> 7.5 mm). Intraosseous tophi were well seen, either being entirely within the bone or having a cortical breach and erosion [51, 52]. DECT has been shown to reliably identify uric acid kidney stones by exploiting the photon energy dependent attenuation of different materials, and the same technique can be used to identify uric acid crystals in the joints or in the periarticular structures [53, 54]. y analyzing the difference in attenuation observed in tissue exposed to two different x-ray spectra simultaneously (80 and 140 kvp, respectively) the composition of materials can be determined (Figs. 7 and 7C). This can be achieved with two x-ray tubes scanning simultaneously. Second-generation scanners use a tin filter for the high-energy 140-kVp tube, which increases the separation of the two x-ray spectra. lternatively, a single-source scanner can be used with rapid switching between the two kilovoltage energies. Choi et al. [55] evaluated 20 patients with gout (10 with aspiration-proven gout), and multiple color-coded urate deposits were identified, whereas no urate deposition was present in the 10 control patients with other forms of arthritis. DECT was able to find 440 areas of urate deposition in the 20 patients, compared with only 111 areas found by physical examination. Nicolaou et al. [56] found DECT to be a useful diagnostic tool in the management of gout in the acute setting. In five clinically challenging cases presenting to the emergency department, four patients had positive DECT scans, despite normal serum uric acid levels in three patients, and the diagnosis was confirmed with aspiration of uric acid crystals. Glazebrook et al. [57] evaluated the accuracy of DECT in detecting MSU crystals in patients with suspected gout, using joint aspiration within 1 month of DECT as the reference standard. Two readers who were blinded to the aspiration results classified the DECT as positive or negative. The sensitivity was 100% (95% CI, %), and specificity was 79 89% (95% CI, 54 99%). There was nearly perfect agreement between the two readers (κ = 0.87; 95% CI, ). In a prospective validation study, Choi et al. [58] used DECT to evaluate 40 patients with crystalproven gout and 40 control subjects. Specificity and sensitivity were 0.93 (95% CI, ) and 0.78 (95% CI, ), respectively. The lower sensitivity may be due to frequent use of urate-lowering therapy in the patients with gout. Interobserver and intraobserver intraclass correlation coefficients for DECT volume measurements of tophi were 1.00 (95% CI, ) and 1.00 (95% CI, ), respectively. ongartz et al. [59] performed a prospective accuracy and diagnostic yield study. To assess the sensitivity and specificity of DECT for diagnosing gout, two cohorts were used: a control cohort with no history of gout who underwent synovial aspiration for other types of joint disease and a cohort of patients with active gout diagnosed with positive polarizing and electron microscopy who were stratified according to joint location and duration of symptoms (either less than 6 weeks or 6 weeks or more). The sensitivity and specificity of DECT were 0.93 (95% CI, ) and 0.95 (95% CI, ), respectively. ll three falsenegative cases were in patients with acute podagra of less than 6 weeks duration and no prior episodes of joint pain. In these patients, the MSU deposits may be too small to register. The two false-positive cases were in knees with advanced osteoarthritis, and DECT signal indicated intracartilaginous uric acid deposition. This has been shown to occur pathologically but does not signify clinical gout. third cohort of patients, with high clinical suspicion of gout but in whom an aspiration could not be obtained or who had a negative aspiration result, was also studied. DECT showed evidence for MSU crystal deposition in 14 of 30 patients (47%). Ultrasound-guided reaspiration of areas with positive DECT findings confirmed the presence of MSU crystals in 11 of 12 patients. Entheses were a common location for MSU de- JR:201, September

4 Girish et al. Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved position in patients with previously negative aspiration: chilles tendon, plantar fascia, patellar tendon, or triceps tendon insertion sites. Dalbeth et al. [49] also found frequent tendon involvement, most commonly the chilles tendon and enthesis, in patients with long-standing tophaceous gout. DECT can be used for identification of MSU deposits to guide aspiration and improve diagnostic yield. Dalbeth et al. [60] identified several methods of tophus assessment in clinical trials of chronic gout. Physical measurements were more feasible than advanced imaging methods in the general practice setting; however, they do not allow assessment of intraarticular or deep tophi. DECT can accurately assess these deeper tophi, and, with the use of dedicated automated volume assessment software, can measure MSU crystal volumes in the extremities. Direct quantitative measurement of MSU volume can be made with DECT software, so reduction in actual MSU burden following successful treatment can be documented with serial DECT scans [62]. DECT scans of patients receiving urate-lowering therapy still show the soft-tissue tophaceous masses, corresponding to the residual inflammatory response to the MSU crystals, whereas the MSU crystals themselves have been dissolved (Fig. 8). IV contrast agent can be administered to evaluate for inflammatory change. DECT bone removal and iodine mapping can be used to aid in the visualization of synovitis and tenosynovitis. rtifacts occur, particularly in the feet and ankles, with green pixels in the skin of the heel and in the nails due to dense callous and thickened nails, particularly in the great toe (Fig. 9). These do not interfere with diagnostic confidence, because they are superficial and not periarticular in location. The technique is not accurate in large joints, such as the shoulder or hip, or in the thoracic spine because the low-peak-kilovoltage images (80 or even 100 kvp) have too much noise. Motion or metal artifact can also cause artifactual green pixilation. DECT can have false-negative scans in very early acute gout if there is insufficient uric acid crystal volume or if the tophi are too small to be detected [62]. DECT has the potential to differentiate gout from other crystal deposition, such as calcium pyrophosphate deposition disease or pseudogout [55, 56]. Subclinical MSU deposits may also be seen in patients without clinical evidence for acute gout. MRI Underutilization of MRI in the diagnosis and management of gout may be due to the limited availability of MRI and its relatively high cost. The true diagnostic accuracy of MRI in gout is yet to be determined [63]. MRI is effective in evaluation of extremity abnormalities because it can show abnormalities of both soft-tissue and osseous structures. One advantage of MRI over ultrasound is that deeper structures and other areas not visible by ultrasound, including intraosseous gout deposits, are easily identified. lthough MRI is indeed very sensitive in the identification of a soft-tissue or bone abnormality, the findings may not be specific for one diagnosis, as is often the case with gout [38]. MRI cannot specifically identify MSU crystals. Often it is the site of involvement, distribution, and history that are clues to the correct diagnosis. The MRI features of gout are variable (Fig. 10). Tophi have intermediate or low signal intensity on T1-weighted images and heterogeneous signal intensity on T2-weighted or fluid-sensitive sequences, possibly because of the presence of variable amounts of calcium [4, 64]. Tophi can show uniform enhancement or show a nonenhancing center [4, 65]. one erosions adjacent to tophi can produce cortical destruction and variable bone marrow edema. ecause of the somewhat nonspecific features of gout on MRI, clues to the correct diagnosis are site of involvement and distribution of findings. The foot, more specifically the medial aspect of the distal first metatarsal, is a common site of involvement. Other potential sites of involvement in the foot include the midfoot (Fig. 11). ecause cortical erosions may also be seen with osteomyelitis, the lack of an adjacent softtissue ulcer is an important finding that suggests the diagnosis of gout. nother common site of gout involvement is the knee (Fig. 12). s stated earlier, there are specific tendons about the knee that are commonly involved with gout, such as the popliteus (Fig. 6) and patellar (Fig. 13) tendons. In the latter situation, the intratendinous tophus may present as a mass and clinically may appear as a soft-tissue malignancy. MRI also has an established role in imaging and evaluating spinal involvement in gout [66]. Summary dvanced imaging using ultrasound, DECT, and MRI can show soft-tissue and bone changes that are characteristic of gout, related to MSU crystal deposition and adjacent inflammation. In addition, both ultrasound and DECT have imaging findings that are often specific for gout, such that these noninvasive diagnostic studies may be considered an alternative to joint aspiration for the diagnosis of gout in many cases. Gout commonly involves specific joints and anatomic structures, which is often a clue to the correct diagnosis. dvanced imaging may also be potentially useful in assessing response to treatment. References 1. Schwartz S. Disease of distinction. Explore (NY) 2006; 2: Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. 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6 Girish et al. 62. Glazebrook KN, Kakar S, Ida CM, Laurini J, Moder KG, Leng S. False-negative dual-energy computed tomography in a patient with acute gout. J Clin Rheumatol 2012; 18: Dalbeth N, Doyle J. Imaging of gout: an overview. est Pract Res Clin Rheumatol 2012; 26: Chen CK, Chung C, Yeh L, et al. Carpal tunnel syndrome caused by tophaceous gout: CT and MR imaging features in 20 patients. JR 2000; 175: Popp JD, idgood WD Jr, Edwards NL. Magnetic resonance imaging of tophaceous gout in the hands and wrists. Semin rthritis Rheum 1996; 25: Hsu CY, Shih TT, Huang KM, Chen PQ, Sheu JJ, Li YW. Tophaceous gout of the spine: MR imaging features. Clin Radiol 2002; 57: Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with pain in first metacarpophalangeal joint and known history of gout. Ultrasound image along long axis of first metacarpophalangeal joint shows multiple echogenic foci (short arrows) floating in joint effusion. Echogenic tophus (asterisk) is noted causing osseous erosion (long arrows). Fig year-old man who presented with gout and pain of right great toe., Ultrasound along long axis of first metatarsophalangeal joint shows echogenic line (arrows) over anechoic articular cartilage, known as double contour sign, over metatarsal head. Small joint effusion (asterisk) is also noted., Ultrasound image of contralateral asymptomatic great toe shows normal appearance of hyaline cartilage (arrows). Small joint effusion (asterisk) is also noted. Fig year-old woman with gout. Long-axis ultrasound image of first metatarsophalangeal joint shows hyperechoic synovial hypertrophy with monosodium urate crystal deposits and peripheral anechoic rim (thick long arrows), intrinsic hypoechoic streaks (small arrows), and hyperechoic foci (thin long arrow). 520 JR:201, September 2013

7 Imaging of Gout Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old woman with great toe pain and history of gout., Long-axis ultrasound image of first metatarsophalangeal joint shows erosion (arrows) with cortical discontinuity, irregularity, and peripheral overhanging edge. Note echogenic synovitis (asterisks) and multiple hyperechoic foci (arrowheads) from monosodium urate crystal deposition., Oblique foot radiograph shows multiple erosions (arrows) and soft-tissue tophi (asterisks). Note normal bone density and relative preservation of joint space until late in disease process, in affected first metatarsophalangeal joint. Note also characteristic overhanging edges and sclerotic margins involving some of these erosions. Fig year-old man with gout deposition in ankle tendons. and, Long-axis ultrasound image of chilles () and peroneus brevis () tendons show hyperechoic deposits (arrows) within substance of tendon. Peroneus longus is partially visualized. Fig year-old man with knee pain., Long-axis ultrasound image of lateral knee shows echogenic tophi involving popliteus tendon (large asterisks) adjacent to popliteus groove (large arrow) with smaller tophi (small asterisk) involving lateral collateral ligament (LCL). Note erosion (small arrow) at femoral attachment of LCL., xial T1-weighted MRI shows intermediate-signal-intensity tophus involving popliteus tendon (large arrows) and erosion of popliteus groove (small arrows). (Fig. 6 continues on next page) JR:201, September

8 Girish et al. Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 6 (continued) 66-year-old man with knee pain. C, nteroposterior radiograph shows tophus as increased soft-tissue density (large arrows) adjacent to erosion of popliteus groove (small arrows). C Fig year-old man with right ankle pain., Coronal multiplanar reformmated 2D CT image of right ankle and foot shows high-attenuation tophi associated with erosions in distal tibia, fibula, and talus., xial 2D dual-energy CT (DECT) with color mapping shows uric acid deposits (green) in periarticular tissues of ankle, extending into erosion in anterior fibula. C, Three-dimensional DECT with color mapping shows uric acid depositions (green) within ankle joint and midfoot. C 522 JR:201, September 2013

9 Imaging of Gout Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old woman with 15-year history of gout and history of treatment with urate-lowering therapy who presented with acute swelling of left second toe., Coronal mixed-kilovoltage dual-energy CT (DECT) of left foot shows mineralized soft-tissue tophi at first metatarsophalangeal joint, with adjacent erosions and intraosseous tophi (arrows). and C, Coronal () and sagittal (C) DECT with color mapping images show minimal green pixilation, representing monosodium urate crystals, at first metatarsophalangeal joint tophi, consistent with treated gout. Clump of green pixilation (circles), consistent with acute gout, is seen in soft tissues of second toe. Fig year-old man with history of gout., Three-dimensional reconstruction dual-energy CT (DECT) with color mapping shows artifactual green pixilation (arrows) in region of first toe nail bed and in regions of skin callus at heel and first ray., Surface rendering from DECT shows that artifactual green pixilation (arrows) is in skin at sites of callus. C JR:201, September

10 Girish et al. Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved D E Fig year-old man referred for amputation of forefoot for mass., Radiograph of right foot shows soft-tissue mass (asterisks) adjacent to right first metatarsophalangeal joint (arrows)., Sagittal T1-weighted MRI of right forefoot shows intermediate-signal-intensity soft-tissue mass (asterisks) surrounding first metatarsophalangeal joint, with adjacent erosion in first metatarsal head (arrow). C and D, Coronal inversion recovery (C) and contrastenhanced spoiled gradient T1-weighted fat-saturated MRI (D) of forefoot through level of metatarsal heads show enhancing and heterogeneous soft-tissue masses (asterisks). E, Three-dimensional rendered dual-energy CT with color mapping shows extensive monosodium urate (MSU) crystal deposition (green) consistent with tophaceous gout about first metatarsophalangeal joint, with additional unsuspected MSU deposition in ankle and midfoot. Fig year-old man with foot pain and gout. and, Coronal T1-weighted () and sagittal STIR () MRI scans show multiple tophi and erosions of tarsal bones (arrows), which appear as intermediate signalintensity on T1-weighted and STIR images. C 524 JR:201, September 2013

11 Imaging of Gout Downloaded from by on 12/30/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with knee pain and limitation of movements., Sagittal T1-weighted MRI shows intermediate-to-low-signal-intensity tophi (arrows) involving cruciate ligaments., Sagittal T2-weighted image with fat saturation shows tophi (arrows) at attachment site of semimembranosus tendon. Note joint effusion (small asterisk) and aker cyst (large asterisk). Fig year-old woman with history of anterior knee mass., Sagittal T1-weighted MRI shows low-to-intermediate-signal-intensity mass (asterisks) infiltrating patellar tendon., Sagittal T2-weighted MRI with fat saturation shows predominantly high-signal-intensity mass (asterisks). rrow denotes joint effusion. C, Sagittal T1-weighted MRI with fat saturation after IV contrast administration shows peripheral rim enhancement (asterisks) that extends into infrapatellar fat pad of Hoffa (arrowhead) and inferior patellar pole (short arrow). Note joint effusion (long arrow). C JR:201, September