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      Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability using radiomic analysis of coronary computed tomography angiography

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          Abstract

          Aims

          Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability.

          Methods and results

          We prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF 18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65–0.78 vs. 0.59, CI: 0.57–0.62; P < 0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72–0.88 vs. 0.66, CI: 0.58–0.73; P < 0.001), and NaF 18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82–0.91 vs. 0.65, CI: 0.64–0.66; P < 0.001).

          Conclusion

          Coronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted.

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          Most cited references19

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          Detecting human coronary inflammation by imaging perivascular fat.

          Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis method and studied CT images of human adipose tissue explants from 453 patients undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan information on the biology of the explants. We developed an imaging metric, the CT fat attenuation index (FAI), that describes adipocyte lipid content and size. The FAI has excellent sensitivity and specificity for detecting tissue inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a validation cohort of 273 subjects, the FAI gradient around human coronary arteries identified early subclinical coronary artery disease in vivo, as well as detected dynamic changes of PVAT in response to variations of vascular inflammation, and inflamed, vulnerable atherosclerotic plaques during acute coronary syndromes. Our study revealed that human vessels exert paracrine effects on the surrounding PVAT, affecting local intracellular lipid accumulation in preadipocytes, which can be monitored using a CT imaging approach. This methodology can be implemented in clinical practice to noninvasively detect plaque instability in the human coronary vasculature.
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            American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents.

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              Radiomics of CT Features May Be Nonreproducible and Redundant: Influence of CT Acquisition Parameters

              Purpose To identify the reproducible and nonredundant radiomics features (RFs) for computed tomography (CT). Materials and Methods Two phantoms were used to test RF reproducibility by using test-retest analysis, by changing the CT acquisition parameters (hereafter, intra-CT analysis), and by comparing five different scanners with the same CT parameters (hereafter, inter-CT analysis). Reproducible RFs were selected by using the concordance correlation coefficient (as a measure of the agreement between variables) and the coefficient of variation (defined as the ratio of the standard deviation to the mean). Redundant features were grouped by using hierarchical cluster analysis. Results A total of 177 RFs including intensity, shape, and texture features were evaluated. The test-retest analysis showed that 91% (161 of 177) of the RFs were reproducible according to concordance correlation coefficient. Reproducibility of intra-CT RFs, based on coefficient of variation, ranged from 89.3% (151 of 177) to 43.1% (76 of 177) where the pitch factor and the reconstruction kernel were modified, respectively. Reproducibility of inter-CT RFs, based on coefficient of variation, also showed large material differences, from 85.3% (151 of 177; wood) to only 15.8% (28 of 177; polyurethane). Ten clusters were identified after the hierarchical cluster analysis and one RF per cluster was chosen as representative. Conclusion Many RFs were redundant and nonreproducible. If all the CT parameters are fixed except field of view, tube voltage, and milliamperage, then the information provided by the analyzed RFs can be summarized in only 10 RFs (each representing a cluster) because of redundancy.
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                Author and article information

                Journal
                Eur Heart J Cardiovasc Imaging
                Eur Heart J Cardiovasc Imaging
                ehjcimaging
                European Heart Journal Cardiovascular Imaging
                Oxford University Press
                2047-2404
                2047-2412
                November 2019
                05 March 2019
                05 March 2019
                : 20
                : 11 , Focus Issue: Imaging in Chronic Coronary Syndromes
                : 1250-1258
                Affiliations
                [1 ] Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University , 68. Varosmajor street, Budapest, Hungary
                [2 ] Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital , 101 Daehang-ro, Chongno-gu, Seoul, Republic of Korea
                [3 ] Department of Nuclear Medicine, Seoul National University Hospital , 101 Daehang-ro, Chongo-gu, Seoul, Republic of Korea
                [4 ] Department of Internal Medicine and Cardiovascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine , Gangnam-gu, Irwon-dong, Seoul, Republic of Korea
                [5 ] Icahn School of Medicine at Mount Sinai Hospital , 1 Gustave L. Levy Place, New York, NY, USA
                [6 ] Department of Cardiovascular Medicine, Wakayama Medical University , 811-1 Kimiidera, Wakayama, Wakayama Prefecture, Japan
                Author notes
                Corresponding author. Tel: +82 (2) 2072 2062; Fax: +82 (2) 3675 0805. E-mail: bkkoo@ 123456snu.ac.kr
                Article
                jez033
                10.1093/ehjci/jez033
                6806259
                30838375
                d8c17ed8-1aa1-47f8-bca2-957967b7a489
                © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 17 October 2018
                : 13 February 2019
                Page count
                Pages: 9
                Funding
                Funded by: Ministry of Health & Welfare
                Funded by: Republic of Korea
                Award ID: HI14C1277
                Funded by: National Research, Development and Innovation Office of Hungary
                Award ID: NVKP-16-1-2016-0017
                Funded by: Ministry of Human Capacities in Hungary
                Funded by: Semmelweis University 10.13039/501100002332
                Categories
                RISK ASSESSMENT IN CHRONIC CORONARY SYNDROMES
                Original Article
                Editor's Choice

                Cardiovascular Medicine
                radiomics,coronary ct angiography,intravascular ultrasound,optical coherence tomography,sodium-fluoride positron emission tomography

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