Objective: To evaluate the potential utility of a dual energy CT (DECT) scan in assessing urate deposits among patients with tophaceous gout, and obtain computerised quantification of tophus volume in peripheral joints.
Methods: 20 consecutive patients with tophaceous gout and 10 control patients with other arthritic conditions were included. DECT scans were performed using a renal stone colour-coding protocol that specifically assessed the chemical composition of the material (ie, urate coloured in red, calcium coloured in blue). An automated volumetric assessment of DECT was used to measure the volume of urate deposits in all peripheral joint areas.
Results: All 20 patients with gout showed red colour-coded urate deposits on their DECT scans, whereas none of 10 controls showed urate deposits. DECT scans revealed a total of 440 areas of urate deposition in 20 patients, whereas physical examination showed 111 areas of urate deposition (mean 22 vs 6 per patient, respectively, p<0.001). Total urate volume in a given patient ranged from 0.63 cm3 to 249.13 cm3, with a mean of 40.20 cm3.
Conclusions: DECT scans can produce obvious colour displays for urate deposits and help to identify subclinical tophus deposits. Furthermore, tophus volume can be measured by DECT scans through an automated volume estimation procedure.
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Gout is a common inflammatory arthritis that is triggered by the crystallisation of uric acid within the joints and is often associated with hyperuricaemia.1 The overall disease burden of gout remains substantial and is growing.2 3 While studies have suggested the potential clinical utility of conventional imaging modalities for gout,4 5 6 7 8 9 none of these modalities specifically identifies the chemical composition of uric acid.
A specific display algorithm based on the chemical composition of uric acid by dual energy CT (DECT) scans may provide an accurate imaging tool for gout.10 Recently, DECT, an established imaging modality for detecting cardiovascular calcifications,11 has also been shown to identify uric acid renal stones and specifically differentiate these from other types of renal stones both in vivo and in vitro.12 The authors performed DECT scans using colour coding for dual energy properties of three materials (ie, uric acid (red), calcium (blue) and water (gray)) on retrieved renal calculi of known chemical composition, and showed that all uric acid stones were colour-coded in red, and all calcified stones were blue. The authors also confirmed that DECT scans provided the same colour-differential display between uric acid and calcium stones when applied to actual patients with urolithiasis.12
In this study, we evaluated the potential utility of DECT in assessing uric acid deposits among patients with tophaceous gout, and computerised quantification of tophus volume in peripheral joints.
Patients and methods
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.
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).
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.
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.
The authors thank the rheumatology and radiology faculty members of the University of British Columbia for providing patient information and valuable comments for the study.
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Funding HKC holds the Mary Pack Arthritis Society of Canada Chair in Rheumatology and has received research funding from TAP Pharmaceuticals for other research projects. In addition, HKC has received honoraria from and serves as a consultant to TAP Pharmaceuticals and Savient.
Competing interests None.
Ethics approval Approval from Vancouver General Hospital Ethics Committee.
▸ An additional table and figure are published online only at http://ard.bmj.com/content/vol68/issue10