Review
FOCUS ON: Musculoskeletal Imaging
August 23, 2013

Advanced Imaging in Gout

Abstract

OBJECTIVE. 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.
Acute gouty arthritis of the first metatarsophalangeal joint, termed “podagra,” was first identified by Egyptians in 2640 B.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). At 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. Although 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 [57]. 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 2007–2008; the prevalence of hyperuricemia was much greater (21.4%).

Cause and Associations

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].
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 inter-leukin-1 mediated [16]. MSU crystals trigger interleukin-1β production in macrophages by activating the NALP3 inflammasome pathway [1719]. 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 [2123], diabetes mellitus [24], and premature death [22, 25]. Reduction in morbidity in gout can be brought about by early definitive diagnosis and effective management. Assessment 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 WBC 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]. “Atypical” 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. Soft-tissue 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.
Fig. 1 —57-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).
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). Although 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. According to other studies, the sensitivity of this finding in patients with gout ranges from 25% to 95% [3438]. 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].
Fig. 2A —65-year-old man who presented with gout and pain of right great toe.
A, 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.
Fig. 2B —65-year-old man who presented with gout and pain of right great toe.
B, Ultrasound image of contralateral asymptomatic great toe shows normal appearance of hyaline cartilage (arrows). Small joint effusion (asterisk) is also noted.
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.
Fig. 3 —80-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).
Erosions are seen in long-standing gout, usually next to tophi (Fig. 4). Tophi can activate 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. Active 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).
Fig. 4A —68-year-old woman with great toe pain and history of gout.
A, 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.
Fig. 4B —68-year-old woman with great toe pain and history of gout.
B, 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.

Ultrasound Findings: Bursa and Subcutaneous Tissues

Ultrasound is able to clearly depict tophaceous deposits in bursa, tendons, ligaments, and soft tissues. A 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]. A 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%). A small proportion of the patients had primarily intratendinous deposits. Knowledge of preferred tendon involvement can also be helpful in the diagnosis of gout. The Achilles and pero-neal 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.
Fig. 5A —61-year-old man with gout deposition in ankle tendons.
A, Long-axis ultrasound image of Achilles (A) and peroneus brevis (B) tendons show hyperechoic deposits (arrows) within substance of tendon. Peroneus longus is partially visualized.
Fig. 5B —61-year-old man with gout deposition in ankle tendons.
B, Long-axis ultrasound image of Achilles (A) and peroneus brevis (B) tendons show hyperechoic deposits (arrows) within substance of tendon. Peroneus longus is partially visualized.
Fig. 6A —66-year-old man with knee pain.
A, 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.
Fig. 6B —66-year-old man with knee pain.
B, Axial T1-weighted MRI shows intermediate-signal-intensity tophus involving popliteus tendon (large arrows) and erosion of popliteus groove (small arrows).
Fig. 6C —66-year-old man with knee pain.
C, Anteroposterior radiograph shows tophus as increased soft-tissue density (large arrows) adjacent to erosion of popliteus groove (small arrows).

CT

CT allows excellent 2D and 3D representation of the bone and soft tissues. Tophi are seen as discrete masses with a density of 160–170 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. 7A). 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].
Fig. 7A —42-year-old man with right ankle pain.
A, Coronal multiplanar reformmated 2D CT image of right ankle and foot shows high-attenuation tophi associated with erosions in distal tibia, fibula, and talus.
Fig. 7B —42-year-old man with right ankle pain.
B, Axial 2D dual-energy CT (DECT) with color mapping shows uric acid deposits (green) in periarticular tissues of ankle, extending into erosion in anterior fibula.
Fig. 7C —42-year-old man with right ankle pain.
C, Three-dimensional DECT with color mapping shows uric acid depositions (green) within ankle joint and midfoot.
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]. By 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. 7B 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. Alternatively, 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, 74–100%), and specificity was 79–89% (95% CI, 54–99%). There was nearly perfect agreement between the two readers (κ = 0.87; 95% CI, 0.70–1.00). In a prospective validation study, Choi et al. [58] used DECT to evaluate 40 patients with crystal-proven gout and 40 control subjects. Specificity and sensitivity were 0.93 (95% CI, 0.80–0.98) and 0.78 (95% CI, 0.62–0.89), 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, 1.00–1.00) and 1.00 (95% CI, 1.00–1.00), respectively.
Bongartz 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, 0.79–0.98) and 0.95 (95% CI, 0.82–0.99), respectively. All three false-negative 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. A 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 deposition in patients with previously negative aspiration: Achilles tendon, plantar fascia, patellar tendon, or triceps tendon insertion sites. Dalbeth et al. [49] also found frequent tendon involvement, most commonly the Achilles 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.
Fig. 8A —58-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.
A, 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).
Fig. 8B —58-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.
B, Coronal (B) 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. 8C —58-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.
C, Coronal (B) 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.
Artifacts 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.
Fig. 9A —67-year-old man with history of gout.
A, 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.
Fig. 9B —67-year-old man with history of gout.
B, Surface rendering from DECT shows that artifactual green pixilation (arrows) is in skin at sites of callus.

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. Although 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]. Bone erosions adjacent to tophi can produce cortical destruction and variable bone marrow edema.
Fig. 10A —70-year-old man referred for amputation of forefoot for mass.
A, Radiograph of right foot shows soft-tissue mass (asterisks) adjacent to right first metatarsophalangeal joint (arrows).
Fig. 10B —70-year-old man referred for amputation of forefoot for mass.
B, 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).
Fig. 10C —70-year-old man referred for amputation of forefoot for mass.
C, Coronal inversion recovery (C) and contrast-enhanced spoiled gradient T1-weighted fat-saturated MRI (D) of forefoot through level of metatarsal heads show enhancing and heterogeneous soft-tissue masses (asterisks).
Fig. 10D —70-year-old man referred for amputation of forefoot for mass.
D, Coronal inversion recovery (C) and contrast-enhanced spoiled gradient T1-weighted fat-saturated MRI (D) of forefoot through level of metatarsal heads show enhancing and heterogeneous soft-tissue masses (asterisks).
Fig. 10E —70-year-old man referred for amputation of forefoot for mass.
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.
Because 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). Because cortical erosions may also be seen with osteomyelitis, the lack of an adjacent soft-tissue ulcer is an important finding that suggests the diagnosis of gout. Another common site of gout involvement is the knee (Fig. 12). As 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].
Fig. 11A —56-year-old man with foot pain and gout.
A, Coronal T1-weighted (A) and sagittal STIR (B) MRI scans show multiple tophi and erosions of tarsal bones (arrows), which appear as intermediate signal-intensity on T1-weighted and STIR images.
Fig. 11B —56-year-old man with foot pain and gout.
B, Coronal T1-weighted (A) and sagittal STIR (B) MRI scans show multiple tophi and erosions of tarsal bones (arrows), which appear as intermediate signal-intensity on T1-weighted and STIR images.
Fig. 12A —64-year-old man with knee pain and limitation of movements.
A, Sagittal T1-weighted MRI shows intermediate-to-low-signal-intensity tophi (arrows) involving cruciate ligaments.
Fig. 12B —64-year-old man with knee pain and limitation of movements.
B, Sagittal T2-weighted image with fat saturation shows tophi (arrows) at attachment site of semimembranosus tendon. Note joint effusion (small asterisk) and Baker cyst (large asterisk).
Fig. 13A —56–year-old woman with history of anterior knee mass.
A, Sagittal T1-weighted MRI shows low-to-intermediate-signal-intensity mass (asterisks) infiltrating patellar tendon.
Fig. 13B —56–year-old woman with history of anterior knee mass.
B, Sagittal T2-weighted MRI with fat saturation shows predominantly high-signal-intensity mass (asterisks). Arrow denotes joint effusion.
Fig. 13C —56–year-old woman with history of anterior knee mass.
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).

Summary

Advanced 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. Advanced imaging may also be potentially useful in assessing response to treatment.

References

1.
Schwartz SA. Disease of distinction. Explore (NY) 2006; 2:515–519
2.
Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford) 2007; 46:1116–1121
3.
So A, Busso N. Update on gout 2012. Joint Bone Spine 2012; 79:539–543
4.
Yu JS, Chung C, Recht M, Dailiana T, Jurdi R. MR imaging of tophaceous gout. AJR 1997; 168:523–527
5.
Agudelo CA, Wise CM. Gout: diagnosis, pathogenesis, and clinical manifestations. Curr Opin Rheumatol 2001; 13:234–239
6.
Fam AG. Gout in the elderly: clinical presentation and treatment. Drugs Aging 1998; 13:229–243
7.
Richette P, Bardin T. Gout. Lancet 2010; 375:318–328
8.
Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2007; 57:109–115
9.
Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008; 58:26–35
10.
Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum 2011; 63:3136–3141
11.
Zhang Y, Chen C, Choi H, et al. Purine-rich foods intake and recurrent gout attacks. Ann Rheum Dis 2012; 71:1448–1453
12.
Joosten LA, Netea MG, Mylona E, et al. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1beta production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum 2010; 62:3237–3248
13.
Monu JU, Pope TL Jr. Gout: a clinical and radiologic review. Radiol Clin North Am 2004; 42:169–184
14.
Davis JC Jr. A practical approach to gout: current management of an “old” disease. Postgrad Med 1999; 106:115–116, 119–123
15.
Fam AG. What is new about crystals other than monosodium urate? Curr Opin Rheumatol 2000; 12:228–234
16.
Di Giovine FS, Malawista SE, Nuki G, Duff GW. Interleukin 1 (IL 1) as a mediator of crystal arthritis: stimulation of T cell and synovial fibroblast mitogenesis by urate crystal-induced IL 1. J Immunol 1987; 138:3213–3218
17.
Agudelo CA, Schumacher HR. The synovitis of acute gouty arthritis: a light and electron microscopic study. Hum Pathol 1973; 4:265–279
18.
Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 2006; 116:2262–2271
19.
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237–241
20.
Crittenden DB, Pillinger MH. New therapies for gout. Annu Rev Med 2013; 64:325–337
21.
Abbott RD, Brand FN, Kannel WB, Castelli WP. Gout and coronary heart disease: the Framing-ham Study. J Clin Epidemiol 1988; 41:237–242
22.
Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation 2007; 116:894–900
23.
Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum 2006; 54:2688–2696
24.
Choi HK, De Vera MA, Krishnan E. Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology (Oxford) 2008; 47:1567–1570
25.
Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH. Long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med 2008; 168:1104–1110
26.
Swan A, Amer H, Dieppe P. The value of synovial fluid assays in the diagnosis of joint disease: a literature survey. Ann Rheum Dis 2002; 61:493–498
27.
Schlesinger N, Baker DG, Schumacher HR Jr. Serum urate during bouts of acute gouty arthritis. J Rheumatol 1997; 24:2265–2266
28.
Singh JA, Hodges JS, Toscano JP, Asch SM. Quality of care for gout in the US needs improvement. Arthritis Rheum 2007; 57:822–829
29.
Klauser AS, Peetrons P. Developments in musculoskeletal ultrasound and clinical applications. Skeletal Radiol 2010; 39:1061–1071
30.
Filippucci E, Meenagh G, Delle Sedie A, et al. Ultrasound imaging for the rheumatologist. Part XXXVI. Sonographic assessment of the foot in gout patients. Clin Exp Rheumatol 2011; 29:901–905
31.
Schueller-Weidekamm C, Schueller G, Aringer M, Weber M, Kainberger F. Impact of sonography in gouty arthritis: comparison with conventional radiography, clinical examination, and laboratory findings. Eur J Radiol 2007; 62:437–443
32.
Rettenbacher T, Ennemoser S, Weirich H, et al. Diagnostic imaging of gout: comparison of high-resolution US versus conventional X-ray. Eur Radiol 2008; 18:621–630
33.
de Miguel E, Puig JG, Castillo C, Peiteado D, Torres RJ, Martin-Mola E. Diagnosis of gout in patients with asymptomatic hyperuricaemia: a pilot ultrasound study. Ann Rheum Dis 2012; 71:157–158
34.
Wright SA, Filippucci E, McVeigh C, et al. High-resolution ultrasonography of the first metatarsal phalangeal joint in gout: a controlled study. Ann Rheum Dis 2007; 66:859–864
35.
Filippucci E, Riveros MG, Georgescu D, Salaffi F, Grassi W. Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease: an ultrasound study. Osteoarthritis Cartilage 2009; 17:178–181
36.
Howard RG, Pillinger MH, Gyftopoulos S, Thiele RG, Swearingen CJ, Samuels J. Reproducibility of musculoskeletal ultrasound for determining monosodium urate deposition: concordance between readers. Arthritis Care Res (Hoboken) 2011; 63:1456–1462
37.
Pineda C, Amezcua-Guerra LM, Solano C, et al. Joint and tendon subclinical involvement suggestive of gouty arthritis in asymptomatic hyperuricemia: an ultrasound controlled study. Arthritis Res Ther 2011; 13:R4
38.
Thiele RG. Role of ultrasound and other advanced imaging in the diagnosis and management of gout. Curr Rheumatol Rep 2011; 13:146–153
39.
Ottaviani S, Allard A, Bardin T, Richette P. An exploratory ultrasound study of early gout. Clin Exp Rheumatol 2011; 29:816–821
40.
Thiele RG, Schlesinger N. Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved. Rheumatol Int 2010; 30:495–503
41.
Filippucci E, Scire CA, Delle Sedie A, et al. Ultrasound imaging for the rheumatologist. Part XXV. Sonographic assessment of the knee in patients with gout and calcium pyrophosphate deposition disease. Clin Exp Rheumatol 2010; 28:2–5
42.
de Ávila Fernandes E, Kubota ES, Sandim GB, Mitraud SA, Ferrari AJ, Fernandes AR. Ultrasound features of tophi in chronic tophaceous gout. Skeletal Radiol 2011; 40:309–315
43.
McQueen FM, Chhana A, Dalbeth N. Mechanisms of joint damage in gout: evidence from cellular and imaging studies. Nat Rev Rheumatol 2012; 8:173–181
44.
Wakefield RJ, Balint PV, Szkudlarek M, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 2005; 32:2485–2487
45.
Dalbeth N, Pool B, Gamble GD, et al. Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum 2010; 62:1549–1556
46.
Chowalloor PV, Keen HI. A systematic review of ultrasonography in gout and asymptomatic hyperuricaemia. Ann Rheum Dis 2013; 72:638–645
47.
Perez-Ruiz F, Martin I, Canteli B. Ultrasonographic measurement of tophi as an outcome measure for chronic gout. J Rheumatol 2007; 34:1888–1893
48.
de Ávila Fernandes E, Sandim GB, Mitraud SA, Kubota ES, Ferrari AJ, Fernandes AR. Sonographic description and classification of tendinous involvement in relation to tophi in chronic tophaceous gout. Insights Imaging 2010; 1:143–148
49.
Dalbeth N, Kalluru R, Aati O, Horne A, Doyle AJ, McQueen FM. Tendon involvement in the feet of patients with gout: a dual-energy CT study. Ann Rheum Dis 2013 [Epub ahead of print]
50.
Ko KH, Hsu YC, Lee HS, Lee CH, Huang GS. Tophaceous gout of the knee: revisiting MRI patterns in 30 patients. J Clin Rheumatol 2010; 16:209–214
51.
Dalbeth N, Clark B, Gregory K, et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis 2009; 68:1290–1295
52.
McQueen FM, Reeves Q, Dalbeth N. New insights into an old disease: advanced imaging in the diagnosis and management of gout. Postgrad Med J 2013; 89:87–93
53.
Primak AN, Fletcher JG, Vrtiska TJ, et al. Noninvasive differentiation of uric acid versus non-uric acid kidney stones using dual-energy CT. Acad Radiol 2007; 14:1441–1447
54.
Graser A, Johnson TR, Bader M, et al. Dual energy CT characterization of urinary calculi: initial in vitro and clinical experience. Invest Radiol 2008; 43:112–119
55.
Choi HK, Al-Arfaj AM, Eftekhari A, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis 2009; 68:1609–1612
56.
Nicolaou S, Yong-Hing CJ, Galea-Soler S, Hou DJ, Louis L, Munk P. Dual-energy CT as a potential new diagnostic tool in the management of gout in the acute setting. AJR 2010; 194:1072–1078
57.
Glazebrook KN, Guimaraes LS, Murthy NS, et al. Identification of intraarticular and periarticular uric acid crystals with dual-energy CT: initial evaluation. Radiology 2011; 261:516–524
58.
Choi HK, Burns LC, Shojania K, et al. Dual energy CT in gout: a prospective validation study. Ann Rheum Dis 2012; 71:1466–1471
59.
Bongartz T, Glazebrook K, Kavros S, et al. Diagnosis of gout using dual-energy computed tomography: an accuracy and diagnostic study. Arthritis Rheum 2011; 63(suppl 10): 1617
60.
Dalbeth N, Schauer C, Macdonald P, et al. Methods of tophus assessment in clinical trials of chronic gout: a systematic literature review and pictorial reference guide. Ann Rheum Dis 2011; 70:597–604
61.
Bacani AK, McCollough CH, Glazebrook KN, et al. Dual energy computed tomography for quantification of tissue urate deposits in tophaceous gout: help from modern physics in the management of an ancient disease. Rheumatol Int 2012; 32:235–239
62.
Glazebrook KN, Kakar S, Ida CM, Laurini JA, Moder KG, Leng S. False-negative dual-energy computed tomography in a patient with acute gout. J Clin Rheumatol 2012; 18:138–141
63.
Dalbeth N, Doyle AJ. Imaging of gout: an overview. Best Pract Res Clin Rheumatol 2012; 26:823–838
64.
Chen CK, Chung CB, Yeh L, et al. Carpal tunnel syndrome caused by tophaceous gout: CT and MR imaging features in 20 patients. AJR 2000; 175:655–659
65.
Popp JD, Bidgood WD Jr, Edwards NL. Magnetic resonance imaging of tophaceous gout in the hands and wrists. Semin Arthritis Rheum 1996; 25:282–289
66.
Hsu CY, Shih TT, Huang KM, Chen PQ, Sheu JJ, Li YW. Tophaceous gout of the spine: MR imaging features. Clin Radiol 2002; 57:919–925

Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 515 - 525
PubMed: 23971443

History

Submitted: February 14, 2013
Accepted: April 8, 2013

Keywords

  1. academic research faculty
  2. dual-energy low-kilovoltage CT
  3. gout
  4. hospital
  5. MRI
  6. musculoskeletal imaging
  7. musculoskeletal system–appendicular

Authors

Affiliations

Gandikota Girish
Department of Radiology, University of Michigan Hospitals, 1500 E Medical Center Dr, TC 2910, Ann Arbor, MI 48109-0326.
Katrina N. Glazebrook
Department of Radiology, Mayo Clinic, Rochester, MN.
Jon A. Jacobson
Department of Radiology, University of Michigan Hospitals, 1500 E Medical Center Dr, TC 2910, Ann Arbor, MI 48109-0326.

Notes

Address correspondence to G. Girish ([email protected]).

Metrics & Citations

Metrics

Citations

Export Citations

To download the citation to this article, select your reference manager software.

Articles citing this article

View Options

View options

PDF

View PDF

PDF Download

Download PDF

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media