European Radiology (2019) 29:1267–1275 https://doi.org/10.1007/s00330-018-5716-4 MUSCULOSKELETAL Combining non-contrast and dual-energy CT improves diagnosis of early gout Seul Ki Lee1,2 & Joon-Yong Jung1 & Won-Hee Jee1 & Jennifer Jooha Lee3 & Sung-Hwan Park3 Received: 6 May 2018 /Revised: 17 July 2018 /Accepted: 14 August 2018 /Published online: 17 September 2018 # European Society of Radiology 2018 Abstract Objectives To determine the incremental value of non-contrast CT (NCCT) on dual-energy CT (DECT) in symptomatic first metatarsophalangeal (MTP) joints in early gout. Methods One hundred and fifteen painful joints were consecutively enrolled and gout was diagnosed based on the 2015 EULAR/ACR criteria and/or arthrocentesis. Two readers independently evaluated DECT alone and combined NCCT and DECT (NCCT+DECT) based on four semiquantitative scales. Sensitivities and specificities were compared using McNemar’s test. AUC was compared. Results Of the 115 joints, 72 were defined as an early gout group and 43 as a gout-negative group after exclusion. The sensitivity and specificity for the early gout group on DECTalone were as followed: reader 1 – 52.8% and 100.0% and reader 2 – 51.4% and 100.0%. NCCT+DECT results were as follows: reader 1 – 79.2% and 93.0% and reader 2 – 79.2% and 95.3%. AUC was significantly higher in NCCT+DECT compared to that in DECT alone for the early gout group (0.888 vs. 0.774 for reader 1, p = 0.0004; 0.896 vs. 0.816 for reader 2, p = 0.0142). The false-negative cases on DECToccurred more frequently with the first-onset gout, and tended to be affected by a longer duration of symptoms in the post-hoc analysis. Conclusion The combined analysis of NCCT and DECT improves diagnostic capabilities in symptomatic early gout involving the first MTP joint. Key Points • MSU crystal depositions in early gout may be seen on non-contrast CT, while still being undetectable by DECT. • Combining non-contrast CT and DECT improves detection of early gout. • False negatives of DECT are more common than previously reported in cases of first-onset gout. Keywords Gout . Metatarsophalangeal joint . Tomography, x-ray computed . Dual-energy CT . Uric acid Abbreviations DECT Dual-energy computed tomography ACR American College of Rheumatology EULAR European League Against Rheumatism AUC Area under receiver operating characteristic curve classification CPPD Calcium pyrophosphate deposition disease MSU Monosodium urate MTP Metatarsophalangeal NCCT Non-contrast computed tomography * Joon-Yong Jung ROC Receiver operating characteristic [email protected] 1 Department of Radiology, Seoul St. Mary’s Hospital, College of Introduction Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea 2 Present address: Department of Radiology, Dongguk University Ilsan Gout is an inflammatory arthritis in which monosodium urate Hospital, Gyenggi-do 10326, Republic of Korea (MSU) crystals are deposited in joints, cartilage and soft tissues 3 Division of Rheumatology, Department of Internal Medicine, Seoul [1]. The course of gout includes recurrent attacks in intercritical St. Mary’s Hospital, College of Medicine, The Catholic University of periods since the initial attack and chronic tophaceous gout [2]. Korea, Seoul 06591, Republic of Korea The classic presentation of acute gout is ‘podagra’ or pain 1268 Eur Radiol (2019) 29:1267–1275 affecting the first metatarsophalangeal (MTP) joint, which is Clinical characteristics related to gout were obtained from the seen in approximately half of the cases [3]. Prompt diagnosis medical records including gender, age, duration of symptoms, and timely initiation of therapy in its early stage are critical in serum uric acid level, and the presence of a previous medication preventing progressive joint destruction [4, 5]. history for remission of acute flare such as non-steroidal anti- The diagnosis of gout is based on microscopically detecting inflammatory drugs (NSAIDs) and/or colchicine [14]. negatively birefringent needle-shaped MSU crystals found in synovial fluid. However, aspiration of the joint can be challeng- DECT examination and image reconstruction ing, especially in patients with small amounts of joint fluid. Dual-energy computed tomography (DECT) is an alternative All scans were performed using a first-generation DECT sys- modality for diagnosing gout, showing MSU crystals [6–8]. tem (Somatom Definition64; Siemens Healthineers) equipped Due to its high sensitivity and specificity for gout, it has been with two x-ray tubes using tube A, 140 kVand 55mA; tube B, recently included into the 2015 European League Against 80 kV and 243 mA; pitch, 0.7; gantry rotation time, 1.0 s. Rheumatism classification (EULAR)/American College of Automated attenuation-based tube current modulation was Rheumatology (ACR) criteria for gout [9]. However, many used in all DECT scans with average radiation doses of studies included chronic tophaceous gout, the diagnosis of 10.3 mGy (0.03 mSv) for the foot and ankle. All scans were which is clinically obvious without DECT [6–8]. More recent obtained without an intravenous contrast agent. Both feet were studies have excluded chronic tophaceous gout and DECT scanned simultaneously in a supine position. Axial images demonstrated low sensitivities [10–13]. Therefore, the diagnos- were reconstructed with both dual-energy soft tissue kernel tic value of DECT in early gout requires further assessment. (D30s) and standard soft tissue kernel (B30s) with a a slice DECT provides virtually both grey-scale reformation sim- thickness of 0.75 mm. In addition, we used regular grey-scale ilar to non-contrast images and colour-coded material-specific reformations from 140 kVp tube energy using kernel B30s for images. Our hypothesis is that virtual grey-scale reformatted routine diagnostic interpretation on a picture archiving and non-contrast CT can complement colour-coded images of communication system. We also synthesised grey-scale CT DECT in detecting crystal deposition in the early stages of images with weighted energies (40% of 80 kV images mixed gout. Therefore, this study was designed to investigate the with 60% of 140 kV images). These CT images were virtual diagnostic benefit of non-contrast CT to complement colour- non-contrast CT images (namely, NCCT), which served as an coded DECT in symptomatic first MTP joints in early gout. alternative to conventional polychromatic 120 kV single- energy CT images for detection of bony erosions, hyperdense deposits, and other pathologies [15]. The reconstructed axial Material and methods images of both tubes with kernel D30s were loaded onto a multi-modality workspace (Gout, Syngo Dual Energy, Study patients Siemens Healthineers, Erlangen, Germany). The software em- ploys a material decomposition algorithm to identify uric acid This study was approved by the institutional review board of and calcium voxels according to their material-specific dual our hospital, which allowed us to waive the requirement of energy properties. A colour-coded display was used for easy patient informed consent for the retrospective design. distinction of uric acid shown as green, cortical bone as blue, Inclusion criteria were as follows: (i) history or presence of and medullary bone as pink. The colour-coded materials were clinical manifestation of podagra and (ii) DECT screening of overlaid on both multi-planar reformatted cross-sectional and both feet with our DECT protocol for gout between April 3D volume rendering images (namely, DECT). Post- 2015 and August 2017. For each patient, index joints were processing for generation of material-specific images takes limited to the first MTP joints (according to the definition of approximately 2 min. ‘podagra’). Both affected joints in single patient were classi- fied as individual samples. 208 symptomatic joints were con- Image analysis secutively sampled from 180 patients. Exclusion criteria were established for the purpose of isolating early gout from treated Two musculoskeletal radiologists (J.Y.J. and S.K.L. with 8 and chronic tophaceous gout as follows: (i) presence of pal- and 2 years of experience in musculoskeletal radiology, re- pable tophi (n = 24), (ii) presence of characteristic erosions on spectively) who were blinded to the patient’s clinical data radiographs (n = 4), and (iii) known gout under urate-lowering independently reviewed the images by two separate reading therapy (n = 65). Therefore, 93 joints were excluded. Final sessions: DECT alone, and then NCCT and DECT combina- diagnosis of an individual case was based on the 2015 tion (NCCT+DECT). In the first session, the presence of green EULAR/ACR criteria by two rheumatologists (S.H.P. and colour-coded voxels was analysed with four-scale semiquan- J.H.L with 25 and 8 years of experience in rheumatology, titative scores for MSU crystals in the index joint as follows: respectively) and/or synovial fluid aspiration (Fig. 1)[9]. grade 1, absence of green colour-coded voxels; grade 2, Eur Radiol (2019) 29:1267–1275 1269 Fig. 1 Flowchart summarising the inclusion of patients and joints in the study with the reference of standard from the 2015 EULAR/ACR guideline and/ or arthrocentesis presence of green colour-coded voxels regarded as artifacts of DECT or NCCT were positive unless positive NCCT (including skin artifacts, metallic artifacts, beam hardening showed blue colour-coded voxels on DECT. from dense cortical bone, or motion artifacts); grade 3, small sized green colour-coded voxels less than or equal to two Statistical analysis consecutive slices; grade 4, definite green colour-coded voxels more than two consecutive slices (Table 1). Cases with The sensitivity, specificity and accuracy of two reading ses- blue colour-coded voxels in the index joint were regarded as sions for the early gout group were compared using negative; however, they were recorded separately. Cases with McNemar’s test. The area under the receiver operating char- a grade of more than 2 were considered positive. At the second acteristic curve (AUC) based on the four-semiquantitative session, NCCT was analysed with four-scale semiquantitative scale was also compared.