The Clinical Application Of Dual-energy Computed Tomography In The Assessment Of Urate Crystal Deposition Within Gouty Arthritis

Part one:Dual-energy computed tomography for the diagnosis of gout by detecting monosodium urate crystals deposition:an accuracy study[Objective]The aim of the study was to investigate the clinical application value of dual-energy computed tomography in the diagnosis of gouty arthritis, including the sensitivity, specificity, positive predictive value and negative predictive value and analyse the related influencing factors for monosodium urate crystals depositon.[Materials and Methods]1.Study subjectsA total of one hundred and fifty-five patients, who experienced arthrocele and (or) joint pain and agreed to undergo DECT scans, were recruited from Imaging Center of Nan-fang Hospital in Guangzhou between December 2012 and March 2015. DECT scans of all affected peripheral joints(ie,hands and wrists, elbows, knees, ankles and feet) were performed. One hundred and twenty one patients who conformed to the gout classification criteria approved by the American College of Rheumatology(ACR) and European League Against Rheumatism(EULAR) meeting were defined as the gout group. The rest (thirty-four) of the patients with other arthritic conditions were regarded as the non-gout group. The clinical features of all study subjects, such as age, gender, disease duration(from first time sick to the nearest),serum uric acid(SUA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were collected by completion of a questionnaire or checked by review.2.DECT scanningA 64-row dual-source CT scanner (Somatom Definition; Siemens, Germany) equipped with two X-ray tubes and detectors was used. In upper extremity scans, patients were positioned head first in a prone position. Forearms and wrists were positioned forward of the patient’s head with hands in a neutral position. Palms were placed with the dorsum facing up in a relaxed dorsiflexion position. In lower extremity scans, patients were positioned feet first in a supine position, with the knees bent approximately in a 90° position, with the feet in a firmplantarflexion position. The scan parameters were as follows:tube A:140 kV, tube B:80 kV, collimation 64×0.6 mm, pitch 0.7; dual-energy tube current parameters were different according to the scanned anatomical region:tube A reference (ref.) milliampere second (mAs) =40, tube B ref. mAs=170, for hands and wrists; and tube A ref. mAs=55, tube B ref. mAs=234, for ankles, feet and knees. All scans were obtained without intravenous contrast agent. Transverse sections were reconstructed from the DE datasets, with a slice thickness of 0.75 mm and with a composition of 0.3 in the soft tissue kernel (D30).3.DECT data post-processingThe transverse datasets of both tubes(80 kV or 140 kV) were loaded onto Syngo MultiModality Work-place and reconstructed with a dual-energy gout protocol that specifically assessed the chemical composition of the material.The material-specific differences in attenuation of the two datasets (80 and 140 kVp) enabled an easy classification of the elementary chemical composition of the scanned tissue, allowing accurate characterization of uric acid (color coded in green) separately from the calcium and bone marrow (cortical bone color coded in blue and medullary bone in pink). DECT images were evaluated by two senior radiologists. The readers were blinded to the patients’ clinical data. They read the images independently in the workplace. The readers were asked to classify the examination findings as positive or negative for the presence of MSU crystals, record the places of urate deposition.4.Statistic analysisSPSS (Statistical Package for the Social Sciences) 19.0 was used in all statistical analysis.All tests used a two-tailed significance level of 0.05.4.1 All clinical characteristics data was expressed as mean±standard deviation (x±s). Two independent sample t-tests was performed with age, disease duration, serum uric acid(SUA), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) between gout patients and non-gout patients; Pearson chi-square test was performed with sex between two groups. All tests used a two-tailed significance level of 0.05.4.2 The presence of green-coloured voxels in articular or periarticular structures of the scanned peripheral joints(feet/ankles,knees and hands/wrists) was classified as positive for the presence of MSU crystals deposition. Regarding the international recognized gout classification standards as the gold standard,the sensitivity, specificity, positive predictive value, negative predictive value of DECT scanning for the detection of MSU deposition were calculated.4.3 Logistic regression was used to analyse the likely related influencing factors for monosodium urate crystals depositon., including the age, gender, disease duration, serum uric acid concentration, ESR and CRP.[Results]1.clinical characteristics:There were 110 males and 11 females in gout group. The age of gout patients was 49.48±16.62(range 13～86 years);disease duration was 5.21±5.72 years(range 0.03～30 years); the serum uric acid levels was for 483.78±140.62(range 163～871) νmol/L. There were 26 males and 8 females in non-gout group. The age of non-gout patients was 50.06±14.59 (range 17～73) years;disease duration was 1.51±1.76 years(range 0.03～7 years); the serum uric acid levels was for 357.41±107.52 (range 120.7～547) μmol/L.2.Gout group and non-gout clinical baseline data comparison results:age, ESR and CRP difference between the two groups had no statistical significance; the disease duration, serum uric acid concentration, between the two groups was statistically significant; Gender composition difference between two groups have statistical significance.3.High uric acid hematic disease group 78 examples, the high uric acid hematic disease group of 53 cases, testing results of two groups of DECT difference was statistically significant.4. The sensitivity, specificity, positive predictive value, and negative predictive value of DECT scanning for the detection of MSU deposition in the diagnosis of gouty arthritis were 87.6%,88.2%,96.4%and 66.7%, respectively.5.The result of logistic regression analysis was that only serum uric acid concentration(OR=1.01,95%CI:1.00-1.01,P=0.001) have a certain influence for monosodium urate crystal deposition.[Conclusions]1. The detection of MSU crystal deposition by DECT shows higher sensitivity and specific in the diagnosis of gouty arthritis and differential diagnosis between gouty arthritis and other types of arthritis (such as rheumatoid arthritis, pseudo-gout, etc.), when gout is suspected, but polarising microscopy of synovial fluid analysis fails to conform or demonstrate the absence of MSU crystals, DECT can be used as an auxiliary diagnosis method on clinical decision;2. DECT in different parts of the peripheral joints, the accuracy of the diagnosis of gout is different, foot MSU crystal deposition test the accuracy of the diagnosis of gout is better;DECT check in the ankle and knee when specific degree is higher, but the wrist joint pain in patients with the differential diagnosis of gout or rheumatoid arthritis specific degree is low;3.DECT provides good diagnositic accuracy for detection of monosodium urate deposits in patient with gout,but sensitivity is lower in patients with recent-onset disease;4. The risk factor for MSU crystal deposition is serum uric acid levels, reasonably lowering urate treatment should be made reasonably.Part two:Assessment of quantitative measurement of urate crystal deposition with chronic gout by dual-energy computed tomography: reproducibility analysis[Objective]The aim of this study is to evaluate the intraobserver and interobserver reproducibility for DECT urate volume measurements using an automated volume assessment software(volume) and analyse the relationship between MSU crystal volume and clinical characteristics.[Materials and Methods]1.Study subjectsA total of 68 patients with chronic gout were recruited from Imaging Center of Nan-fang Hospital in Guangzhou between December 2012 and March 2015. All patients had a history of acute gout according to the Wallace et al. classification criteria and were detected to have tophi in either the hands, knees, or feet on DECT by two independent musculoskeletal radiologists. Out of the 68 patients,40 underwent CT scans of the feet/ankles,13 for the hands/wrists, and 15 for the knees. The clinical characteristics relating to gout were obtained including age, gender, disease duration and serum urate.2.DECT scanningDECT scans were performed as Part one.3.MSU crystal volume measurementVolumes of monosodium urate(MSU) crystal deposition were measured using a dedicated automated volume assessment software (VOLUME, Siemens, Germany) by two independent observers.These observers were blinded to the results of each other.They circled the entire bodily region to determine total urate volume scpcrately. Single tophus volume measurement, through before the rough position of the tophus, in its place on the cross-section of freehand sketch tophus area, and record the location of tophi (divided into joints, bone and soft tissue tophi);Total urate volume measurement, the wrist or ankle department in all cross-sectional all structure (including bone and soft tissue) sketch into the measurement area. CT values range for-100 HU--1 HU, and then the uric acid composition of calculation obtained by volume. Volumes of monosodium urate(MSU) crystal deposition were measured twice with at least 1 week between measurement by the same observer who were blinded to the result measured by the other observer, the final results and statistical conducted by the third one. For bone erosion or tophus is inconsistent, measurement after the completion of the above two doctors agree after discussion. Record each patient at the same time a measure of the total time spent, timing from the beginning of the image transferred to the workstation, to the end of the measuring closed image.4.Statistic analysisAnalysis was performed using SPSS (Statistical Package for the Social Sciences) 19.0.A11 tests were two tailed, and p value less than 0.05 were considered statistically significant.4.1 The total tophus MSU crystal volumes were measured by two assessment levels (assessment 1 and assesment 2) by two independent readers (valuator 1 and valuator 2) which were included in analyzing intraobserver and interobserver reproducibility using intraclass correlation coefficients (ICCs) with 95% confidence interval (95% CI) and Bland-Altman plots.4.2. Spearman correlation coefficients and liner regression were used to analyze the relationships between MSU crystal volumes and age, serum uric acid(SUA), and disease duration. All analyses were summarized by tophus locations to determine whether the anatomical site was relative to variability in the results. All tests were double tailed at the 0.05 significant levels.[Results]1.Clinical characteristics:There were 63(92.6%) males and 5(7.4%) females in 68 chronic gout patients. The age of them was 52.75±15.53(range 23-86 years);disease duration was 7.6±6.45 years(range 1±30 years); the serum uric acid levels was for 514.5±144.5(range 207～760) μmol/L.2.Consistency analysis results:Total urate crystal volume to an average of 3449.309±5881.359 mm3.All parts urate volume measurement of intraobserver and interobserver ICC was 1.000 (95% CI:1.000,1.000) and 1.000 (95% CI:1.000, 1.000), the results are consistent with all parts.Bland-Altman plots in measuring the difference between group and group close to zero, shows good consistency.3.The correlation analysis results:all the parts of the overall Spearman correlation analysis, the correlation of age and total urate volume has no statistical significance (r=0.104, P=0.104), and the course of the disease (r=0.626, P<0.001), the concentration of blood uric acid (r=0.485, P<0.001) and total MSU crystallization volume correlation was statistically significant. Spearman correlation analysis, separately according to the different parts of the foot/ankle MSU crystallization volume, respectively, and course of the disease (r=0.578, P<0.001) and SUA (r=0.510, P<0.001) correlation was statistically significant, no statistically significant correlation with age.Hand/wrist MSU crystallization volume, respectively, and course of the disease (r=0.633, P=0.008) and SUA (r=0.779, P<0.001) correlation was statistically significant, no statistically significant correlation with age.Knee MSU crystal volume and duration (r=0.722, P<0.001) correlation was statistically significant, no statistically significant correlation with age and SUA.Multivariate linear regression analysis:the MSU volume as the dependent variable, age, duration and SUA levels as independent variables, the overall analysis of the results for the course of the disease (P=0.023) and blood uric acid concentration (P=0.000) statistically significant correlation with total MSU volume.Analysis according to the sites:duration (P=0.041) and SUA (P=0.003) in foot/ankle MSU crystallization volume statistically significant,to investigate the effects of age had no statistical significance;SUA (P=0.002) hand/wrist MSU volume effect statistically significant size, age and duration of the disease to investigate the effects of no statistical significance;Age, duration and SUA in knee MSU crystal volume has no statistical significance.[Conclusions]1.DECT can be a new advanced and reliable modality to evaluate the tophus urate crystal volume of chronic gout patient.The interobserver and intraobserver ICC values of the measurement of urate volumes are excellent and show the good feasibility of this method.DECT can further give guide to the clinical diagnosis and treatment, auxiliary clinician to evaluate gout patients lowering urate treatment effect and tophi outcome.2.Chronic gouty arthritis MSU crystallization course of the disease and blood uric acid levels were associated with volume, tips to DECT as drop uric acid treatment of auxiliary monitoring tools;3.DECT can be used as a kind of advanced and reliable method to quantitatively evaluate the volume of gouty arthritis urate crystals, and provides guidance for clinical treatment of gout and prevention.