Patients and methods

Study patients

This study included 20 consecutive patients with clinically obvious tophaceous gout (including 10 crystal-proven cases) and 10 consecutive control patients with other joint conditions (five with psoriatic arthritis, two with rheumatoid arthritis, one with pseudogout, one with pigmented villonodular synovitis and one with undifferentiated inflammatory arthritis). Approval by our institutional review board was obtained and informed consent was waived as this study was considered a diagnostic procedure for patient benefit.

DECT imaging evaluation

DECT scans were performed using a modified dual energy renal stone colour-coding protocol that specifically assessed the chemical composition of the material (ie, uric acid coloured in red, calcium coloured in blue).12 Patients received a DECT (Definition 64, Siemens Medical Solutions, Forchheim, Germany) scan of all peripheral joints (ie, elbows, wrists, hands, knees, ankles and feet). The Siemens Definition scanner is equipped with two x-ray tubes and two corresponding detectors, which are angled at 90° to one another on the gantry. The use of two x-ray tubes enables their simultaneous rotation at different energies (80 and 140 kV). This feature allows for the concurrent acquisition of two datasets, essentially eliminating errors due to misregistration of data or patient movement between acquisitions. The two datasets are loaded on a multimodality workstation where a three-dimensional material decomposition algorithm allows accurate characterisation of uric acid (coloured in red) below the black line, from soft tissue and calcium (coloured in blue) above the black line (online figure).

The following scanning parameters were used: tube A, 140 kV/55 mA; tube B, 80 kV/243 mA; and collimation 0.6 mm reconstructed to 0.75 mm thick slices. The visualisation algorithm was further optimised (by changing values in the advanced parameter definition table within the dual energy viewer) as needed. Using a dedicated automated volume assessment software, volumes of uric acid deposition were measured. We measured the volume of urate deposition in each affected area and obtained total uric acid volume by summing the tophus volume in hands/wrists, elbows, feet/ankles and knees. We calculated the prevalence of urate deposition by DECT (coded red) with 95% confidence intervals in our study patients. The number of urate deposits was compared between clinical examination and DECT with the Wilcoxon signed-rank test.

Results

The mean age of the 20 gout patients was 63 years and 15 were male (75%) (online table). Serum uric acid levels around the time of DECT scans ranged from 302 to 701 μmol/l. Seventeen patients (85%) experienced acute gout attacks in the year before the study and the average monthly rate of flares varied between 0 and 3. The mean age of the 10 control patients was 57 years and six were male.

Dual source imaging findings

Representative DECT scan images from our study patients are illustrated in figs 1 and 2. All 20 patients with gout showed red colour-coded urate deposits on their DECT scans (prevalence 100%; 95% CI 83% to 100%) including all aspiration-proven, affected sites in 10 patients. Images of single energy scans taken on the same patients showed an increase in attenuation, a non-specific finding (fig 1). None of the 10 control patients demonstrated urate deposition (prevalence 0%; 95% CI 0% to 31%) (fig 1).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

Demonstration of the implementation of the three material decomposition algorithm in dual energy CT (DECT) scans: (A) with and (B) without the algorithm of the knee joint in a patient with gout; (C) with a sagittal T1-weighted MRI view of the same knee joint; (D) with and (E) without the algorithm for a control patient without gout. The soft tissue mass associated with erosion of the patella (solid arrows) was confirmed to be a uric acid tophus by aspiration/polarised microscopy examination. There is another large uric acid deposit along the posterior cruciate ligament (dashed arrows). The white-circled area in image (A) demonstrates an overlay value of −19.8 (colour-coded red), meaning that it is below the black line in the online figure, representing uric acid. The white-squared area demonstrates an overlay value of +32.3 (colour-coded blue), meaning that it is above the black line in the online figure, representing calcium.

• Download figure
• Open in new tab
• Download powerpoint

Figure 2

Dual energy CT (DECT) images of uric acid deposits in various anatomical locations: (A) hand and wrist, (B) elbow, (C) knee, (D) foot and ankle, (E) metatarsophalangeal joints. With the application of the three material decomposition algorithm, uric acid deposits are depicted in red, whereas calcium in bone is depicted in blue. Lower panel views represent volume-rendered images of DECT scans in various locations: (F) hand/wrist view displaying numerous large tophi (depicted in red) along the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints; (G) elbow joint view showing large tophi in the olecranon bursa of the elbow and other locations (dashed arrows); (H) knee joint view displaying urate deposits in the patellar tendon and prepatellar bursa and other locations (dashed arrows); (I) foot/ankle views illustrating large tophaceous deposits at the first metatarsophalangeal joints and along the right Achilles tendon (arrowheads); (J) corresponding automated tophus volume calculations of the metatarsophalangeal joints.

Extent and distribution of urate deposition according to DECT

DECT scans revealed a total of 440 areas of urate deposition in 20 patients, whereas physical examination showed 111 areas of uric acid deposition (mean, 22 vs 6 per patient, respectively, p<0.001) (table 1). The difference was also apparent in all individual joint areas (p values ⩽0.006). The common locations of uric acid deposition were the metatarsophalangeal joints (85%), knees (85%), ankles (70%), followed by upper extremity joints—wrists (50%), metacarpophalangeal joints (45%) and elbows (40%). Urate deposits were also present in the superficial/deep hand flexor tendons, cruciate and collateral knee ligaments, knee extensor mechanism, and within the mid-foot tarsal articulations (figs 1 and 2).

Computerised quantitative assessment of tophus volume

The apparent colour-coded information of urate deposits on the DECT scans allowed for a computer automated procedure to measure tophi volume. Representative volume-rendered, three-dimensional DECT images of urate deposits are displayed in fig 2. Table 1 summarises tophus volume measured by computerised assessment in each involved area, as well as the total tophus volume in each patient. The total volume in a given patient ranged from 0.63 cm³ to 249.13 cm³ and the mean was 40.20 cm³.

Discussion

In this study of 20 consecutive patients with tophaceous gout, we found that all patients had obvious colour-coded evidence of urate deposition by DECT scans, whereas 10 controls with other types of arthritis did not. DECT scans revealed approximately four times more loci of urate deposits than physical examination. These findings suggest that DECT can be useful in the evaluation of urate deposits in gouty patients, in particular, identifying subclinical tophi. Furthermore, the apparent colour-coded information of the urate deposits in DECT scans allowed for a computer automated procedure to measure the volume of each clinical or subclinical tophus, which can be summed to produce a total volume of urate deposition in peripheral joints of a given patient.

DECT scans carry several potential advantages as a follow-up imaging tool over MRI, which was recently evaluated to quantify tophus size.6 These advantages include a lower cost (∼1/6), a shorter scan time (∼15 min for all peripheral joints), simultaneous scanning of multiple joints, obvious colour-differential display of crystals and minimal influence of positioning. Furthermore, the MRI volume measurement of tophus size involves manual tracing of consecutive MR images.6

The radiation exposure of DECT for peripheral joints imaging is estimated to be minimal. At our institution, the DECT radiation dose is 0.5 mSv of dose per scanned region and the total amount for all peripheral joints per patient ranges from 2 to 3 mSv, which is similar to the annual global per caput average dose due to natural radiation sources (2.4 mSv).13 Furthermore, the fact that the target image areas for gout are radio-insensitive peripheral joints, and the vast majority of patients with gout are predominately middle-aged or elderly men,3 14 provides further support for a minimal risk of radiation associated with this potential modality for gout at a practical level.

The potential applications of this novel technology include establishing the extent of gout by identifying subclinical intra- and extra-articular tophi, evaluation of nodular lesions, diagnosing the concurrent presence of gout in patients with other arthropathies, identifying urate deposits in challenging and atypical anatomical sites of gout, understanding the anatomical distribution of the disease and monitoring the response to treatment through measurement of individual tophus volume and total tophus burden. Of note, OMERACT has proposed tophus regression as a core domain for outcome measures in chronic gout.15 Finally, the obvious colour display and dramatic three-dimensional volume-rendered imaging of the disease allows information to be easily and clearly communicated to clinicians and patients.

While this preliminary study focused on patients with tophaceous gout, future, larger-scale studies to precisely define the sensitivity and specificity of DECT in confirming the presence of urate crystals at various stages of gout would be valuable. Furthermore, prospective determination of intra- and inter-rater reproducibility of DECT in measuring tophus volumes should be done, involving more than one musculoskeletal radiologist at multiple centres. Evaluating DECT as a follow-up tool in actual clinical care of tophaceous gouty patients, specifically in following the treatment response to urate-lowering agents, would also help fulfil the OMERACT filter of truth, discrimination and feasibility.15

In conclusion, our data suggest that DECT scans can produce obvious colour displays for urate deposits and help identify subclinical tophus deposits. Furthermore, tophus volume can be measured by DECT scans through an automated volume estimation procedure.