Objectives: To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods: A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1–3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results: The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early- stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. * Correspondence: email@example.com Jin Shang and Xiao-Hu Li contributed equally to this work. Department of Radiology, The First Affiliated Hospital of Anhui Medical University, 210 Jixi Road, Hefei 230022, Anhui, China Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Shang et al. Advances in Rheumatology (2021) 61:36 Page 2 of 14 Conclusion: DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout. Keywords: Gout, Dual-energy spectral CT, Scoring method, Disease duration, Artifact, Clinical trial Introduction and 83%, respectively . However, currently most Gout is the most common form of inflammatory studies on gout were performed using dual-source arthropathy resulting from monosodium urate (MSU) DECT [8, 12–14]. and the performances of other types crystals deposition . The long-term deposition of of DECT, such as single-source rapid kilovoltage switch- MSU crystals in the joints and periarticular soft tissues ing DECT, and dual-scan single-source CT, were less can contribute to progressive joint destruction, renal studied. Thus, the present study was conducted using failure, and mortality given its association with coronary single-source rapid kilovoltage switching DECT based heart disease, metabolic syndrome, and diabetes [2, 3]. on gemstone spectral imaging (GSI) technology (includ- Early diagnosis and the timely initiation of therapy are ing Discovery CT750HD and Revolution CT, GE Health- imperative to improve the disease outcome of patients care, Milwaukee, WI, USA), in which the single tube was with gout. Gout diagnosis is based on the identification switched between 80 and 140 kVp in less than 0.05 μs. of negative birefringent MSU crystals in the joint fluid Moreover, DECT has a potential role in evaluating or tophi by polarized microscopy. However, this method MSU crystals deposition in patients with gout receiving is seldom used in clinical practice owing to many urate-lowering treatments. At present, urate deposition limitations, such as invasiveness, lack of training, and is assessed by automated volume assessment software, microscopy unavailability . Thus, the clinical but this time-consuming method could not easily meas- utilization of dual-energy computer tomography (DECT) ure the volume of specific deposition sites. Therefore, for gout diagnosis has dramatically increased over the Bayat et al.  developed a semi-quantitative DECT past decade. Image acquisition is based on two different scoring system in a large sample set that allowed the spectra (often 80 and 140 kV) in DECT scanning that evaluation of urate deposition at specific sites of feet/an- can operate at the source or detector level. Dual source– kles. In this scoring system, each scan is divided into dual detector (DECT scanners with two X-ray tubes), four areas, and each area is graded in accordance with single-source rapid kilovoltage switching, twin-beam the maximum amount of urate deposition measured single-source CT with gold filter, and dual-scan single- during visual examination. They found that the DECT source are the most commonly used DECT technologies urate scores are highly correlated with urate volumes . The validity of DECT as a measure for gout diagno- and can differentiate between responders and non- sis has been confirmed in many previously published lit- responders to intensive urate-lowering treatment. In the eratures [6–9]. Currently, DECT has been incorporated current study, we applied this semi-quantitative DECT into the 2015 American College of Rheumatology/European scoring system for the evaluation of urate deposition in League Against Rheumatism gout classification criteria gout and assessed the correlation between the urate de- (ACR /EULAR 2015) based on reliable previously published position scores evaluated by the DECT GSI at feet/an- data and its diagnostic accuracy . kles and the clinical data. Most studies have shown that DECT is a highly accur- Furthermore, the artifacts produced during DECT scan- ate tool for gout diagnosis, but it has limited diagnostic ning and post-processing may lead to false-positive results. accuracy for gout in short-term duration with widely However, the differentiation and clinical importance of ar- varied results. Gamala et al.  conducted a meta- tifacts in DECT for MSU deposition identification are still analysis of 10 studies on the diagnostic accuracy of controversial. Chou et al.  summarized the common ar- DECT and revealed that the pooled sensitivity and speci- tifacts in DECT imaging for gout, such as nail bed artifact, ficity of DECT are 81 and 91%, respectively, whereas the skin artifact, clumpy artifacts along the tendon, beam pooled sensitivity is 55% in patients with recent onset hardening, patient motion during the scan, and urate-like disease (≤6 weeks). In a recent study of 15 patients with pixelations in vascular calcification. Some scholars pro- aspiration-proven gout with a disease duration of within posed that these artifacts are true artifacts [6, 16]. Roddy 1 year, the sensitivity of DECT in identifying MSU de- et al.  and other scholars [6, 18] suggested that nail position was only 26.6% . Conversely, in a study of bed and tendon artifacts have important influence on gout 40 patients in the early course of gout, the sensitivity diagnosis. However, whether this influence is due to true and specificity of DECT for the diagnosis of gout are 90 gouty deposition or an artifact is unknown. Shang et al. Advances in Rheumatology (2021) 61:36 Page 3 of 14 Thus, the aims of our study were: tube voltage of the two systems was switched between 80 and 140 kVp in less than 0.05 μs. In the Discovery to evaluate the sensitivity, specificity, and accuracy of CT750HD DECT system (GE Healthcare, Milwaukee, single-source DECT GSI (Discovery CT750HD and WI, USA), the pitch was 0.984, the beam collimation Revolution CT, GE Healthcare, Milwaukee, WI, USA) was 40 mm, the gantry rotation time was 0.6 s, the slice for the detection of MSU crystal deposition at feet/ thickness was 5 mm, and the reconstruction increment ankles in patients with suspected gout in early (≤1 was 1.25 mm. In the Revolution CT system (GE Health- year), middle (1–3 years), and late (> 3 years) stages; care, Milwaukee, WI, USA), the pitch was 0.992, the to determine the correlation between urate beam collimation was 80 mm, the gantry rotation time deposition evaluated by single-source DECT GSI at was 0.8 s, the slice thickness was 5 mm, and the recon- feet/ankles and clinical data; struction increment was 1.25 mm. Both feet were scanned to investigate whether artifacts affect the diagnostic simultaneously in supine position without an intravenous performance of single-source DECT in gout. contrast agent. DECT GSI translated two sets of absorption projection Methods data to material density projection data and provided Study patients different base material mapping (such as uric acid/calcium Patients with suspected gout of the feet or ankles were pairing, water/iodine pairing, water/calcium pairing, etc.). consecutively included in the retrospective study from Base material concentration imaging can better reflect the December 2016 to December 2020 in the hospital. The content of the corresponding components of the tissue, final gout diagnosis was determined by experienced and the uric acid crystal can be visualized more accurately rheumatologists using the 2015 EULAR/ACR classifica- in the uric acid-based map than that in the calcium-based tion criteria as the reference . Characteristic data, in- map . cluding age, sex, disease duration, body mass index (BMI), serum uric acid (SUA) level at time of DECT (the interval Image analysis between the test of SUA and performance of DECT within Two musculoskeletal radiologists blinded to the patients’ 3 days), urate-lowering treatments (ULT) at time of DECT information independently reviewed the images for the (medication treatment on the day of DECT examination), detection and localization of MSU deposits. Each site Diuretic use at time of DECT, the presence of subcutane- was deemed positive or negative for the presence of ous tophi, erosive disease, renal function described as MSU crystals. One positive presence in a single joint eGFR, time from last gouty attack to DECT examination, was enough to count the patient as having gout. Four and patient-reported concomitant disease (such as hyper- regions were involved in the scoring system: the first st tension, ischemic heart disease, dyslipidemia, and type II metatarsophalangeal (MTP1 ) joints, other joints of the diabetes), were obtained from the medical records. toes (2nd–5th MTP and interphalangeal joints), ankles/ Patients were selected using the following inclusion midfeet, and tendons. Each joint was scored as follows: criteria: patients aged between 20 and 90 years old; pa- 0 = no deposit, 1 = dots, 2 = single deposit, 3 = more than tients undergoing two single-source DECT systems with one deposit. The presence of artifacts at the feet/ankles same technique (Discovery CT750HD and Revolution was also recorded. If discordant results arose after the CT, GE Healthcare, Milwaukee, WI, USA) of their feet consultation of the two readers, the two reviewer and a and ankles; patients in the gout group receiving the final third co-author with more than 30 years of experience in diagnosis using 2015 EULAR/ACR criteria after compre- musculoskeletal radiology jointly re-examined the con- hensive musculoskeletal examinations; patients in the troversial images to achieve a consensus that would be control with the final diagnosis of rheumatoid arthritis, used for final analyses described in this current study. inflammatory polyarthropathy, achilles tendinitis, and psoriatic arthritis. Exclusion criteria for patients were: Statistical analyses relevant foot or ankle trauma, or surgery procedures. The SPSS software version 26.0 (SPSS Inc., Chicago, IL, Moreover, there was no comparison with other imaging USA) and MedCalc statistical software version 19.2.6 methods (ultrasonography, MRI, etc.). (MedCalc Software bvba, Ostend, Belgium) were used Ethical approval was provided by the hospital ethics for statistical analyses. Sensitivity, specificity, and area committee. The study was conducted according to the under receiver operating characteristic curve (AUC) Helsinki Declaration. were calculated. Continuous data were described as means and standard deviation (SD), while categorical DECT examination data were expressed as frequencies and percentages. The All scans were performed using single-source DECT statistical significance for the differences between quantita- systems (Discovery CT750HD and Revolution CT). The tive variables without normal distribution were calculated Shang et al. Advances in Rheumatology (2021) 61:36 Page 4 of 14 by Mann-Whitney test, whereas for those with normal early-stage group; 80.00, 100.00%, and 0.900 in the distribution we used the Student’s t-test. The inter-reader middle-stage group; 82.14, 88.89%, and 0.855 in the late- reliability analyses for the diagnostic performance of DECT stage group, and 66.67, 92.31%, and 0.795 in the total- were assessed using Cohen’s kappa statistic that was inter- stages group, respectively (Table 2 and Additional files 2). preted as follows: the values of 0.00–0.20 representing as The overall diagnostic accuracies of AUC in DECT GSI “slight” reliability; 0.21–0.40 as “fair” reliability; 0.41–0.60 as (Discovery CT750HD and Revolution CT) in the late “moderate” reliability; 0.61–0.80 as “substantial” reliability; and middle stages of gout were higher than that in the and > 0.80 as “almost perfect” reliability. Cramer’sVwas early stage of gout. Moreover, the cross-tabulations of utilized to correlate the DECT findings that indicate the diagnostic performance of DECT based on different dis- presence of MSU crystal deposits at feet/ankles with the ease durations are shown in Additional files 3, 4, 5,and 6. clinical and serological variables. Statistical significance was evaluated by Chi-square and Fisher’s exact test. P <0.05 The inter-reader reliability analyses for the diagnostic was regarded as the statistical significance. performance The values for inter-reader agreements of Discovery Results CT, Revolution CT, and both CT scanners were 0.879, Clinical characteristic 0.867, and 0.874 in the early stage; 0.923, 0.720, and An overall number of 196 patients were recruited in the 0.879 in the middle stage; and 0.853, 0.885, and 0.864 in study. The demographic characteristics of the patients the late stage. The strength of agreements was consid- are shown in Table 1. Among the included patients, 125 ered good or very good. (mean age, 56.16 ± 16.93 years) were examined using the Discovery CT750HD, whereas 71 (mean age, 51.68 ± Measurement of urate deposition using the semi- 17.59 years) were examined using the Revolution CT. quantitative DECT scoring system Mean disease duration was 7.52 ± 7.94 years. A history of The MSU crystals were deposited on MTP1st joints tophus was found in 16.8% (33/196) of patients, and the (1.43 ± 2.06 scores) and ankles/midfeet (1.44 ± 2.32 mean uric acid level at recruitment was 456.11 ± 123.16 scores), followed by tendons (0.71 ± 1.68 scores) and mmol/L. Thirty-seven patients were receiving urate- other joints of the toes (0.54 ± 1.46 scores). The scores lowering treatment during evaluation. There were were significantly higher in patients with a disease dur- significant differences in disease duration, presence of ation of more than 3 years than those with a duration of tophus, and diuretic use between the gout and control less than 3 years (Table 3). groups (P<0.05), and the related outcomes should be interpreted cautiously. Meanwhile, subgroup analysis on Associations between total urate deposit score and gout disease duration was performed regarding the early-, characteristics middle-, and late- stages to reduce the bias. Moreover, Age, presence of tophus, bone erosion, and disease we recorded positive DECT results (Fig. 1) and scored duration significantly affected the total urate score (P < the urate deposition in four locations (MTP1st joints, 0.050), whereas gender, SUA level at time DECT, urate- other joints of the toes, ankles/midfeet, and tendons). lowering treatments, BMI, time from last gouty attack to DECT exam, and renal function did not significantly Diagnostic performance of single-source DECT GSI in affect the total urate score (P > 0.050, Table 4). different stages of gout The sensitivity, specificity, and AUC of single-source Artifacts in gout and non-gout groups DECT GSI in 196 patients for the diagnosis of gout were Four types of artifacts, namely, nail artifact, skin artifact, 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, noise artifact, and vascular calcification, were found in 100.00%, and 0.815 in the middle-stage group; 77.55, the current study (Fig. 3). No statistical difference in the 87.50%, and 0.825 in the late-stage group, and 69.18, detection of these four types of artifacts including nail 94.00%, and 0.816 in the total-stages group, respectively artifact (P = 0.143), skin artifact (P = 0.307), vascular cal- (Table 2 and Fig. 2). The sensitivity, specificity, and cification (P = 0.341), and noise artifact (P = 1.000) was AUC of gout diagnosis using Discovery CT750HD (n = found between the case and control groups (Table 5). 125) were 55.56, 100.00%, and 0.778 in the early-stage Therefore, artifacts do not remarkably affect the diag- group; 59.09, 100.00%, and 0.795 in the middle-stage nostic performance of DECT in gout. group; 75.71, 85.71%, and 0.807 in the late-stage group, and 70.30, 95.83%, and 0.831 in the total-stages group, Discussion respectively (Table 2 and Additional files 1). The sensi- Gout is caused by the deposition of MSU crystals in the st tivity, specificity, and AUC in gout diagnosis using Revo- joints or surrounding tissues, among which, the MTP1 lution CT (n = 71) were 25.00, 93.33%, and 0.592 in the joint is the most common joint involved in gout . Shang et al. Advances in Rheumatology (2021) 61:36 Page 5 of 14 Table 1 Demographic, clinical and serological data for both patients with gout and controls Overall single source DECT Discovery 750HD Revolution CT (Discovery 750HD and Revolution CT) Variables Total Gout Controls P Total Gout Controls P Total Gout Controls P patients patients patients Male/Female 175/21 133/13 42/8 0.161 115/10 94/7 21/3 0.627 60/11 39/6 21/5 0.508 Age (years) 54.54 ± 17.27 56.02 ± 16.98 50.20 ± 17.52 0.163 56.16 ± 16.93 56.65 ± 16.65 54.08 ± 18.28 0.441 51.68 ± 17.59 54.60 ± 17.81 46.62 ± 16.31 0.065 Disease duration (yrs) 6.36 ± 7.07 7.60 ± 7.56 2.75 ± 3.48 0.031 7.52 ± 7.94 8.69 ± 8.27 2.63 ± 3.42 <0.001 4.32 ± 4.59 5.07 ± 4.92 2.95 ± 3.64 0.049 Tophus (n, %) 33 (16.8) 33 (22.6) 0 <0.001* 20 (16.0) 20 (19.8) 0 0.013* 13 (18.3) 13 (28.9) 0 0.001* Erosive disease (n, %) 79 (40.3) 73 (50.0) 6 (12.0) <0.001 60 (48.0) 57 (56.4) 3 (12.5) <0.001 19 (26.8) 16 (35.6) 3 (11.5) 0.054 IHD (n, %) 74 (37.8) 61 (41.8) 13 (26.0) 0.047 47 (37.6) 41 (40.6) 1 (25.0) 0.156 27 (38.0) 20 (44.4) 7 (26.9) 0.143 Hypertension (n, %) 113 (57.7) 93 (63.7) 20 (40.0) 0.003 75 (60) 65 (64.4) 10 (41.7) 0.041 38 (53.5) 28 (62.2) 10 (38.5) 0.053 Type II diabetes (n, %) 84 (42.9) 68 (46.6) 16 (32.0) 0.072 56 (44.8) 49 (48.5) 7 (29.2) 0.087 28 (39.4) 19 (42.2) 9 (34.6) 0.527 Dyslipidemia (n, %) 10 (5.1) 9 (6.2) 1 (2.0) 0.434 47 (37.6) 41 (40.6) 6 (25.0) 0.841 1 (1.4) 1 (2.2) 0 (0) 1.000* Diuretic use (n, %) 39 (19.9) 38 (26.0) 1 (2.0) 0.001 23 (18.4) 23 (22.8) 0 0.007* 16 (22.5) 15 (33.3) 1 (3.8) 0.010 ULT at time of DECT (n, %) 37 (18.9) 35 (24.0) 2 (4.0) 0.004 22 (17.6) 21 (20.8) 1 (4.2) 0.104 15 (21.1) 14 (31.1) 1 (3.8) 0.016 BMI ≥ 28 (n, %) 32 (16.3) 22 (15.1) 10 (20.0) 0.415 21 (16.8) 18 (17.8) 3 (12.5) 0.747 11 (15.5) 4 (8.9) 7 (26.9) 0.092 serum uric acid at time of 456.11 ± 123.16 471.69 ± 119.96 410.64 ± 122.29 0.003 451.54 ± 117.82 466.61 ± 114.98 388.08 ± 110.24 0.005 466.42 ± 126.56 486.62 ± 120.73 431.46 ± 131.11 0.096 DECT, (μmol/L) serum uric acid at time of 435.81 ± 146.94 443.37 ± 145.37 303.50 ± 147.79 0.243 399.73 ± 143.50 409.29 ± 139.69 199.00 0.091 475.40 ± 133.0 480.21 ± 136.71 408.00 0.933 DECT with ULT, (μmol/L) serum uric acid at time of 459.21 ± 118.43 480.62 ± 110.00 415.10 ± 120.90 0.001 462.60 ± 109.24 481.66 ± 103.41 396.30 ± 104.93 0.004 464.02 ± 125.91 489.52 ± 115.11 432.40 ± 133.73 0.081 DECT without ULT, (μmol/L) eGFR 0.012 0.058 0.014 eGFR>90 (n, %) 96 (49.0) 64 (43.8) 32 (64.0) 63 (50.4) 49 (48.5) 14 (58.3) 33 (46.5) 15 (33.3) 18 (69.2) eGFR60–90 (n, %) 64 (32.7) 49 (33.6) 15 (30.0) 42 (33.6) 32 (31.7) 10 (41.7) 22 (31.0) 17 (37.8) 5 (19.2) eGFR<60 (n, %) 36 (18.4) 33 (22.6) 3 (6.0) 20 (16.0) 20 (19.8) 0 16 (22.5) 13 (28.9) 3 (11.5) Abbreviations: IHD ischemic heart disease, ULT urate lowering treatment, BMI body mass index, yrs. years *P value was calculated by Fisher Exact Test Shang et al. Advances in Rheumatology (2021) 61:36 Page 6 of 14 Fig. 1 3D reconstruction (a), uric acid base image (b), calcium base image (c) of the same patient showed the identification of score 3 for st MTP1 in the foot. (d), uric acid base image (e), calcium base image (f) of the same patient showed the identification of score 2 for other joints of the toes in the foot. (g), uric acid base image (h), calcium base image (i) of the same patient showed the identification of score 3 for st MTP1 in the foot for ankle/midfoot in the foot The incidence of gout has been increasing annually with the improvement of living standards and changes in diet . Long-term urate deposition is closely related to diabetes mellitus, coronary heart disease, metabolic disorder, and other diseases, which result in serious complications, including joint destruction . There- fore, the early diagnosis and timely treatment of gout are important for the prognosis of patients with gout. Most of the experimental studies on urate deposition were conducted using dual-source devices [12–14, 22]. The current study used single-source systems (DECT GSI: Discovery CT750HD and Revolution CT) to explore the diagnostic performance of DECT in patients with differ- ent disease durations and correlate urate deposition score with clinical characteristics. Furthermore, whether artifacts have impacts on gout diagnosis was also investigated. Dual-source DECT has been reported as a highly accurate tool for gout diagnosis [6, 7, 9]. However, the studies regarding the diagnostic performance of single- source DECT were rare. Glazebrook et al.  conducted a retrospective study on 12 patients with aspiration- proven gout, and reported that the sensitivity and specificity of dual-source DECT are 100 and 89%, respectively. Jia et al.  concluded that the sensitivity of dual-source DECT is lower by 35.7% in patients with onset gout. Zhang et al.  compared the diagnostic accuracies of dual-source DECT and ultrasonography in patients with different gouty disease durations and re- ported that the sensitivities of DECT for gout within 1 year, 1–3 years, and more than 3 years are 26.6, 66.6, and 90%, respectively. They also revealed that the sensitivity of ultrasonography is remarkably higher than that of dual-source DECT in early gout and suggested ultrason- ography as the first choice for the diagnosis of early- stage gout. By contrast, Bongartz et al.  reported a higher sensitivity of 80% using dual-source DECT in 20 gout patients with symptom duration of < 6 weeks. In the present study, the sensitivities of single-source DECT in middle- and late-stage gout were remarkably higher than that in early-stage gout. The outcomes dem- onstrated that disease duration strongly affects the diag- nostic accuracy of single-source DECT, and DECT has limited diagnostic value in early-stage gout. The results could be explained as follows. First, DECT could only detect the smallest size of 2 mm in diameter Shang et al. Advances in Rheumatology (2021) 61:36 Page 7 of 14 Table 2 Sensitivity and specificity of DECT GSI in different stages of gout Overall single source DECT of Discovery CT Revolution CT Discovery and Revolution Group No. Sensitivity Specificity AUC P* No. Sensitivity Specificity AUC P* No. Sensitivity Specificity AUC P* (95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI) Early stage 49 38.10 96.43 0.673 0.003 22 55.56 100.00 0.778 0.002 27 25.00 93.33 0.592 0.211 (≤1 yr) (18.1–61.6) (81.7–99.9) (0.524–0.800) (21.2–86.3) (75.3–100.0) (0.552–0.925) (5.5–57.2) (68.1–99.8) (0.387–0.775) Middle stage 33 62.96 100.00 0.815 <0.001 26 59.09 100.00 0.795 <0.001 7 80.00 100.00 0.900 <0.001 (≤3 yrs) (42.4–80.6) (54.1–100.0) (0.642–0.928) (36.4–79.3) (39.8–100.0) (0.593–0.927) (28.4–99.5) (15.8–100.0) (0.467–0.999) Late stage 114 77.55 87.50 0.825 <0.001 77 75.71 85.71 0.807 <0.001 37 82.14 88.89 0.855 <0.001 (>3 yrs) (68.0–85.4) (61.7–98.4) (0.743–0.890) (64.0–85.2) (42.1–99.6) (0.701–0.888) (63.1–93.9) (51.8–99.7) (0.700–0.949) Total 196 69.18 94.00 0.816 <0.001 125 70.30 95.83 0.831 <0.001 71 66.67 92.31 0.795 <0.001 (61.0–76.5) (83.5–98.7) (0.754–0.868) (60.4–79.0) (78.9–99.9) (0.753–0.892) (51.0–80.0) (74.9–99.1) (0.682–0.882) Abbreviations: No. number, CI confidence intervals, AUC area under receiver operating characteristic curve, yrs. years * the P values refer to the AUC Shang et al. Advances in Rheumatology (2021) 61:36 Page 8 of 14 Fig. 2 a ROC curve for sensitivity, 1-specificity, and AUC regarding the early-stage of gout with overall single source DECT Discovery and Revolution. b ROC curve for sensitivity, 1-specificity, and AUC regarding the middle-stage of gout with overall single source DECT Discovery and Revolution. c ROC curve for sensitivity, 1-specificity, and AUC regarding the late-stage of gout with overall single source Discovery CT750 HD and Revolution CT. d ROC curve for sensitivity, 1-specificity, and AUC regarding the total-stages of gout with overall single source Discovery CT750 HD and Revolution CT and a minimum volume concentration of 15–20% accuracy is largely attributed to the high MSU crystal vol- [16, 23]. However, the volume of MSU crystals in ume in the late stage of gout [12, 14, 24]. Moreover, the patients with short disease course was small and un- deposition of MSU crystals in the early stage of gout is detected. Thus, the sensitivity of single-source DECT also affected by the active chemotaxis and phagocytosis of is decreased in the early stages of gout. Wu et al. and leukocytes. The detection of single-source DECT for MSU Jia et al.  found a strong relationship between disease crystals might be adversely affected by these chemical duration and MSU crystal volume, which can partly ex- compositions . Future researches should test the reli- plain the higher diagnostic effect of DECT in patients with ability of single-source DECT in early gout and find an late-stage gout. Most studies on gout presented a relatively optimal imaging approach for the identification of MSU long disease duration, and the overall high diagnostic deposits in early-stage disease. Shang et al. Advances in Rheumatology (2021) 61:36 Page 9 of 14 Table 3 Measurement of urate deposition using the semi-quantitative DECT scoring system and the stratification by disease duration Value No. of patients (n, %) Total urate scores (x ± s) Z of duration ≤ P value of 3 yrs versus duration ≤ Score of 0 Score of 1 Score of 2 Score of 3 Score of 4 Score of 5 Score of 6 Overall Disease ≤3 yrs. Disease>3 yrs. duration>3 yrs 3 yrs versus disease duration duration duration>3 yrs duration st MTP 1 joint 65 (44.5) 16 (11.0) 13 (8.9) 15 (10.3) 11 (7.5) 8 (5.5) 18 (12.3) 1.43 ± 2.06 1.13 ± 1.81 2.30 ± 2.26 − 3.085 0.002 Other joints of the toes 116 (79.5) 4 (2.7) 8 (5.5) 6 (4.1) 1 (0.7) 3 (2.1) 8 (5.5) 0.54 ± 1.46 0.10 ± 0.37 1.02 ± 1.93 −2.798 0.005 Ankles/ Midfeet 83 (56.8) 3 (2.1) 13 (8.9) 4 (2.7) 6 (4.1) 6 (4.1) 31 (21.2) 1.44 ± 2.32 1.06 ± 2.10 2.35 ± 2.59 −3.306 0.001 Tendons 111 (76.0) 1 (0.7) 8 (5.5) 8 (5.5) 3 (2.1) 4 (2.7) 11 (7.5) 0.71 ± 1.68 0.48 ± 1.26 1.18 ± 2.10 − 1.996 0.046 All joints and tendons _ 4.12 ± 6.27 2.77 ± 4.16 6.85 ± 7.32 −3.723 <0.001 st Abbreviations: MTP 1 joint the first metatarsophalangeal joint, No. number, yrs. years Shang et al. Advances in Rheumatology (2021) 61:36 Page 10 of 14 Table 4 Associations between total urate deposit score and gout characteristics Factors n Total urate deposit score t/Z/F P-value Age (years) −2.040 0.041 <56 63 4.27 ± 5.78 ≥ 56 83 6.45 ± 7.25 Gender −0.91 0.928 Men 133 5.62 ± 6.87 Women 13 4.38 ± 5.06 Tophus −6.157 <0.001 Yes 33 12.45 ± 7.65 No 113 3.48 ± 4.84 Erosive disease −6.188 <0.001 Yes 73 8.55 ± 7.52 No 73 2.47 ± 3.96 Disease duration (yrs) −3.723 <0.001 ≤ 3 48 2.77 ± 4.16 >3 98 6.85 ± 7.32 Urate at DECT (μmol/L) −1.752 0.080 ≤ 585 26 8.12 ± 7.90 > 585 120 4.94 ± 6.33 ULT use at DECT −1.528 0.127 Yes 35 7.20 ± 7.88 No 111 4.97 ± 6.26 BMI (kg/m ) −0.756 0.450 <28 124 5.53 ± 6.56 ≥ 28 22 5.36 ± 7.73 Time from last gouty attack to −0.883 0.405 DECT examination (day) ≤ 10 66 4.94 ± 6.90 > 10 66 5.45 ± 6.84 Renal function by eGFR 0.981 0.378 ≥ 90 64 4.62 ± 6.06 60–90 49 6.18 ± 6.77 < 60 33 6.21 ± 7.81 The t value, Z value, and F value were obtained by Student’s t-test, Mann-Whitney test, and Analysis of variance, respectively, according to the result of the test for normal distribution Besides, growing evidence shows that DECT can deter- are not correlated with the total urate deposit score, mine disease activity and therapy efficacy in gout . which might be attributed to the fact that for some pa- Bayat et al.  developed a semi-quantitative DECT tients with gout, the SUA levels are in the normal range, scoring method for the evaluation of MSU crystal de- or even lower . Urano et al.  concluded that the posits at specific sites in the feet/ankles during therapy, decrease in SUA during acute gouty arthritis was associ- and the scores were highly correlated with urate ated with increased urinary excretion of uric acid. In volumes. Dalbeth et al.  measured the MSU crystal addition, we also found that there was no correlation of deposition in patients with gout who received stable- use of urate-lowering treatment with the total urate de- dose allopurinol and demonstrated that the higher posit score. Dehlin et al.  showed the suboptimal crystal deposition on DECT was associated with higher treatment using urate-lowering treatment in gout and SUA and lower allopurinol dose. However, the results of suggested that the efficiencies of urate-lowering treat- our study showed that SUA level at time of DECT. ment with long-term periods were limited for patients Shang et al. Advances in Rheumatology (2021) 61:36 Page 11 of 14 treatment for a short time after gout diagnosis. These factors above could explain the unrelatedness of urate- lowering treatment use and the total urate deposit scores. Furthermore, the results of our study also showed that the total urate deposit score was higher in patients with longer disease duration and correlated strongly to the presence of tophus, bone erosion, and disease duration. Similarly, Svensson et al.  applied this urate scoring method and found that the amount of MSU deposits is associated with the presence of tophus and disease duration. Dalbeth et al.  found that higher urate deposits are correlated with tophi and bone erosion. The reason why the presence of tophus, bone erosion, and longer disease duration caused higher amount of urate deposition could be explained by the following reasons. First, disease duration is the major contributor to urate deposition; urate deposition in- creases with disease duration [9, 14]. Second, the pres- ence of tophus is a dominant factor for bone erosion in gout . Moreover, the presence of tophus and bone erosion result in a longer disease duration in patients with gout. There are differences between single- and dual-source DECT. As for the dual-source DECT, two tube-detector pairs are employed and the tube voltages can be adjust- able with the advantage of fast single energy combina- tions. However, the two separate tubes are offset by Fig. 3 a Uric acid base image (a) depicted typical artifact from the nail bed. b Uric acid base image (b) depicted typical artifact from approximately 90° to each other, thereby contributing to the skin. c Uric acid base image (c) depicted typical artifact from the the material decomposition that is required to be per- noise. d Uric acid base image (d) depicted typical artifact from the formed only on the image domain because of the spatial vascular calcification offset between acquisitions . In terms of the single- source rapid kilovoltage switching scanners (Discovery who had difficulties in compliance to the advice of doc- CT750 HD and Revolution CT), there are almost no- tor, thereby contributing to a health care problem of temporal mismatch and full feilds of view with the X-ray urate-lowering treatment management. Moreover, well- tube switching between 80 and 140 kVp in less than 0.2 treated patients are slow “MSU deposit depletors” and ms.  Thus, multiple spectral images are generated by still have substantial urate volumes even after 2 years. projection-space decomposition. As opposed to dual- Patients unevenly reduce their MSU burden after urate- source DECT systems, projection-space decomposition lowering treatment. Thus, adding a density measurement has the advantages of greater flexibility in the types of of MSU crystal deposition to the apparent volume as- materials that can be used of data to minimize beam sessment may help understand the varying kinetics of hardening artifacts . MSU burden depletion [29, 30]. In addition, some of the DECT has limitations in gout diagnosis. First, the arti- patients enrolled in our study used urate-lowering facts are commonly observed in the feet and ankles and Table 5 Presence of artifacts in both patients with gout and controls Group Nailartifact Skinartifact Noise Vascular calcification + – + – + – + – Gout patients 146 67 79 30 116 6 140 1 145 Controls 50 17 31 7 43 0 50 0 50 Cramer’s V 0.105 0.073 0.104 0.042 χ 2.150 1.043 –– P-value 0.143 0.307 0.341* 1.000* *P value was calculated by Fisher Exact Test Shang et al. Advances in Rheumatology (2021) 61:36 Page 12 of 14 might interfere with radiologists’ performance and ex- of MSU crystal deposition in gout but had limited diag- perience. Some scholars believed that tiny scattered nostic sensitivity for short-stage gout. Longer disease green pixelation within tendons may be the result of the duration, the presence of tophus, and bone erosion were subclinical deposition of MSU crystals [6, 18]. Besides, associated with the novel semi-quantitative DECT Chen et al.  demonstrated that nail urate could be a scoring system. Artifacts do not remarkably affect the proxy for the burden of MSU deposition. We found no diagnostic performance of DECT in gout. statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise Supplementary Information The online version contains supplementary material available at https://doi. artifact between the case and control groups. Further- org/10.1186/s42358-021-00194-4. more, the artifacts caused by noise and motion were not seen in the present study, which is probably attributed Additional file 1. a. ROC curve for sensitivity, 1-specificity, and AUC re- to the ultrafast reconstruction algorithms by the scintil- garding the early-stage of gout with Discovery CT750 HD. b. ROC curve for sensitivity, 1-specificity, and AUC regarding the middle-stage of gout lator of the DECT GSI equipment with fast sampling with Discovery CT750 HD. c. ROC curve for sensitivity, 1-specificity, and capabilities (~ 50 μs) . Moreover, the ionizing AUC regarding the late-stage of gout with Discovery CT750 HD. d. ROC radiation of DECT is harmful to patients, although the curve for sensitivity, 1-specificity, and AUC regarding the total-stages of gout with Discovery CT750 HD. radiation doses of DECT are comparable to or even Additional file 2. a. ROC curve for sensitivity, 1-specificity, and AUC re- lower than the dose reference level of body CT . In garding the early-stage of gout with Revolution CT. b. ROC curve for sensi- addition, DECT has been described as a highly accurate tivity, 1-specificity, and AUC regarding the middle-stage of gout with tool for the detection and measurement of disease Revolution CT. c. ROC curve for sensitivity, 1-specificity, and AUC regarding the late-stage of gout with Revolution CT. d. ROC curve for sensitivity, 1- burden and is thus well-suited to evaluate the treatment specificity, and AUC regarding the total-stages of gout with Revolution CT. response of gout. However, the presence of MSU de- Additional file 3. The cross-tabulation of diagnostic performance of posits is not necessarily associated with gout, although DECT in the early stage (≤1 yrs). they increase the risk of its occurrence. Meanwhile, Additional file 4. The cross-tabulation of diagnostic performance of DECT cannot be utilized for the establishment of in- DECT in the middle stage (≤3 yrs). flammation. Thus, DECT can diagnose these deposits Additional file 5. The cross-tabulation of diagnostic performance of DECT in the late stage (>3 yrs). that contribute to the diagnosis of gout instead of dir- Additional file 6. The cross-tabulation of diagnostic performance of ectly diagnosing gout. In the criteria of ACR /EULAR DECT in all the disease durations. 2015, DECT is one of the criteria, not the only and suffi- cient one. Moreover, DECT is not widely available and Acknowledgements only restricted to certain radiology centers. Nevertheless, The authors thank Lu-Ping Zhou for his invaluable assistance in the editing DECT provides material characterization via two or of this manuscript. more X-ray photon energy-dependent attenuation, Authors’ contributions which allows the qualitative and quantitative determin- Jin Shang: Conceptualization, Data curation, Formal analysis, Investigation, ation of MSU deposition in joints and tissues. Further- Methodology, Software, Validation, Visualization, Writing - original draft, more, DECT performs an excellent visualization of Writing - editing. Xiao-hu Li: Conceptualization, Project administration, Data curation, Formal analysis, Methodology, Writing - review. Shu-qin Lu: deeper or complex structures and display the anatomic Conceptualization, Data curation, Formal analysis, Methodology, Supervision, extent of gouty deposits. Validation, Visualization, Writing - review. Yi Shang: Conceptualization, Data This study has several limitations. First, this study was curation, Formal analysis, Methodology, Validation, Visualization, Writing - review. Lu-lu Li: Data curation, Formal analysis, Methodology, Validation, a cross-sectional study and therefore cannot determine Visualization, Writing - review. Bin Liu: Conceptualization, Project the relationship between changes in urate deposition administration, Supervision, Validation, Writing - review. The author(s) read and urate-lowering treatment. Second, no reliable infor- and approved the final manuscript. mation on the characteristics of gout attack, such as the Authors’ information severity and frequency of attacks, was obtained in the Jin Shang: MD, Department of Radiology, the First Affiliated Hospital of medical records. Third, we did not compare our method Anhui Medical University, 210 Jixi Road, Hefei, Anhui 230022, China. Xiao-Hu Li: PhD, Department of Radiology, the First Affiliated Hospital of with other types of DECT techniques to determine any Anhui Medical University, 210 Jixi Road, Hefei, Anhui 230022, China. difference in gout diagnosis. Finally, a few cases were Shu-Qin Lu: MD, Department of Radiology, the First Affiliated Hospital of confirmed by arthrocentesis, which is the gold standard Anhui Medical University, 210 Jixi Road, Hefei, Anhui 230022, China. Yi Shang: MD, Outpatient Department of The Second Central Division, The for gout diagnosis. Alternatively, we utilized the 2015 General Hospital of PLA, 28 Fuxing Road, Beijing 100853, China. EULAR/ACR classification criteria as reference instead Lu-Lu Li: MD, Department of Radiology, the First Affiliated Hospital of Anhui of the invasive method. Medical University, 210 Jixi Road, Hefei, Anhui 230022, China. Bin Liu: MD, Department of Radiology, the First Affiliated Hospital of Anhui Medical University, 210 Jixi Road, Hefei, Anhui 230022, China. Conclusion DECT GSI (Discovery CT750HD and Revolution CT) Funding showed promising diagnostic accuracy for the detection Not applicable. Shang et al. Advances in Rheumatology (2021) 61:36 Page 13 of 14 Availability of data and materials a cross-sectional study in patients with clinically diagnosed gout. Not applicable. Medicine (Baltimore). 2018;97(42):e12834. https://doi.org/10.1097/MD. 14. Jia E, Zhu J, Huang W, Chen X, Li J. Dual-energy computed tomography has Declarations limited diagnostic sensitivity for short-term gout. Clin Rheumatol. 2018;37(3): 773–7. https://doi.org/10.1007/s10067-017-3753-z. Ethics approval and consent to participate Ethical approval was provided by the ethics committees of the First Affiliated 15. Bayat S, Aati O, Rech J, Sapsford M, Cavallaro A, Lell M, et al. Development Hospital of Anhui Medical University Ethics Committee. Since this is a of a dual-energy computed tomography scoring system for measurement retrospective study, formal consent is not required. of Urate deposition in gout. Arthritis Care Res (Hoboken). 2016;68(6):769–75. https://doi.org/10.1002/acr.22754. 16. Melzer R, Pauli C, Treumann T, Krauss B. Gout tophus detection-a Consent for publication comparison of dual-energy CT (DECT) and histology. Semin Arthritis Rheum. Not applicable. 2014;43(5):662–5. https://doi.org/10.1016/j.semarthrit.2013.11.002. 17. Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther. 2010;12(6): Competing interests 223. https://doi.org/10.1186/ar3199. 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Advances in Rheumatology – Springer Journals
Published: Jun 12, 2021
Keywords: Gout; Dual-energy spectral CT; Scoring method; Disease duration; Artifact; Clinical trial