Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Radiol. Aug 28, 2020; 12(8): 184-194
Published online Aug 28, 2020. doi: 10.4329/wjr.v12.i8.184
Quantification of uric acid in vasculature of patients with gout using dual-energy computed tomography
Sharon Hannah Barazani, Wei-Wei Chi, Renata Pyzik, Helena Chang, Adam Jacobi, Tom O’Donnell, Zahi A Fayad, Yousaf Ali, Venkatesh Mani
Sharon Hannah Barazani, Renata Pyzik, Zahi A Fayad, Venkatesh Mani, Department of Radiology, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Wei-Wei Chi, Yousaf Ali, Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Helena Chang, Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Adam Jacobi, Zahi A Fayad, Venkatesh Mani, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Tom O’Donnell, Siemens Healthineers, Erlangen 91052, Germany
Author contributions: Barazani SH prepared the first draft of the manuscript which was then revised critically for content by all authors; Barazani SH, Chi WW, Pyzik R recruited subjects and acquired data; Barazani SH, Chi WW, Pyzik R, Chang H and Mani V analyzed the data; Chi WW, Chang H, Jacobi A, Fayad ZA and Mani V interpreted the data; Chi WW, Jacobi A and Ali Y were responsible for patient safety monitoring; Jacobi A, Fayad ZA, Ali Y and Mani V conceived and designed the study; Mani V will be responsible for accuracy, and integrity of the data.
Institutional review board statement: The study was reviewed and approved by the Icahn School of Medicine at Mount Sinai, Mount Sinai St, Luke’s, Mount Sinai West.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None of the authors have any conflicts of interest with regards to the study.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Venkatesh Mani, PhD, Associate Professor, Department of Radiology, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States. venkatesh.mani@mssm.edu
Received: March 9, 2020
Peer-review started: March 9, 2020
First decision: April 25, 2020
Revised: June 16, 2020
Accepted: July 19, 2020
Article in press: July 19, 2020
Published online: August 28, 2020
Processing time: 167 Days and 14.4 Hours
ARTICLE HIGHLIGHTS
Research background

Gout, caused by hyperuricemia and subsequent deposition of aggregated monosodium urate crystals (MSU) in the joints or extra-articular regions, is the most common inflammatory arthritis. There is increasing evidence that gout is an independent risk factor for hypertension, cardiovascular disease progression and mortality. Gout patients are at higher risk of life-threatening myocardial infarction and stroke. However, the exact mechanisms by which gout confers this increased cardiovascular risk are still poorly understood.

Research motivation

Dual energy computed tomography (DECT) has been previously used to diagnose gout and accurately visualize MSU deposits within the joints. MSU deposits identified by DECT in regions other than the joints, such as the vasculature, have been anecdotally treated as artifacts. However, it is possible that in hyperuricemic individuals, MSU may actually be deposited within the vessel wall and possibly lead to an inflammatory cascade.

Research objectives

The aim of this study was to determine if DECT can quantify deposition of MSU within the vessel wall of individuals with gout and to measure volume of urate deposits to determine if this deposition is increased in these gout patients as compared to healthy controls.

Research methods

Fifty adult subjects were recruited from a single-center urban academic hospital to participate in this study. 31 subjects had gout, and 18 were healthy controls. Of the 31 gout patients, 16 subjects had tophaceous gout, and the remaining 15 were non tophaceous. All study participants underwent dual energy computed tomography (DECT) scans of the chest and abdomen using a second-generation Siemens somatom Force 2 × 192 slice dual source computed tomography scanner. Images were analyzed using a specific segmentation algorithm to differentiate calcium and urate depositions within the arterial vessel wall (aorta, coronaries and iliacs) using the Siemens syngo via software package. Total volume of areas coded green by the DECT material decomposition algorithm (indicating MSU deposition) with the entire aorta was computed using a semi-automated volume assessment program from manually drawn regions of interest. The number of distinct green spots on images within the aorta were also computed. Unadjusted differences in the total volume of MSU and the number of green spots in the aorta between the gout and healthy control groups were assessed via the Mann-Whitney U exact test. An exploratory subgroup analysis was performed to compare differences in total volume and number of green spots between the tophaceous and non-tophaceous gout groups using the nonparametric methods described above.

Research results

Gout subjects had significantly higher volume of MSU within the entire aorta and the number of deposits (green spots on image) was significantly higher in the gout group compared to the controls. However, after adjustment for age, gender, history of cardiovascular disease and diabetes, there was no significant difference between the gout and control groups with respect to MSU volume. Older age was associated with higher total green coded volume on images (P = 0.08) and larger number of green spots (P = 0.03). Exploratory subgroup analysis of tophaceous and non-tophaceous gout showed no significant differences between the groups for either total MSU volume in the aorta (P = 0.63) or the number of green spots (P = 0.55). A significantly larger proportion of subjects in the gout group had MSU deposits in the coronaries and iliac arteries. Specifically, 55% (n = 16/29) of the subjects in the gout group had potential uric acid deposits in the coronary arteries compared to 0% in the control group (P < 0.001).

Research conclusions

The results of this study show that patients with gout have increased green coded regions and MSU deposition within their vasculature and that the total volume of these regions within the aorta of individuals with gout was significantly higher than the controls. Similarly, the proportion of individuals with MSU deposits within the coronary vessels and iliacs was higher in patients with gout compared to controls. To our knowledge, this is amongst the first few studies to demonstrate such a relationship. This study has provided compelling data regarding vascular deposition of MSU in patients with gout and could lead to future studies that examine whether this finding has implications for the increased cardiovascular disease risk in individuals with gout. In the future, this study could benefit from a larger sample size as well as from the availability of serum inflammatory biomarkers and serum urate data for correlating with the results. Further independent confirmatory studies in newly developed animal models or in human cadavers with histological confirmation may also shed light on the sensitivity, specificity, and accuracy of DECT in quantifying vascular urate depositions.