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      Chest Fat Quantification via CT Based on Standardized Anatomy Space in Adult Lung Transplant Candidates

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          Abstract

          Purpose

          Overweight and underweight conditions are considered relative contraindications to lung transplantation due to their association with excess mortality. Yet, recent work suggests that body mass index (BMI) does not accurately reflect adipose tissue mass in adults with advanced lung diseases. Alternative and more accurate measures of adiposity are needed. Chest fat estimation by routine computed tomography (CT) imaging may therefore be important for identifying high-risk lung transplant candidates. In this paper, an approach to chest fat quantification and quality assessment based on a recently formulated concept of standardized anatomic space (SAS) is presented. The goal of the paper is to seek answers to several key questions related to chest fat quantity and quality assessment based on a single slice CT (whether in the chest, abdomen, or thigh) versus a volumetric CT, which have not been addressed in the literature.

          Methods

          Unenhanced chest CT image data sets from 40 adult lung transplant candidates (age 58 ± 12 yrs and BMI 26.4 ± 4.3 kg/m 2), 16 with chronic obstructive pulmonary disease (COPD), 16 with idiopathic pulmonary fibrosis (IPF), and the remainder with other conditions were analyzed together with a single slice acquired for each patient at the L5 vertebral level and mid-thigh level. The thoracic body region and the interface between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in the chest were consistently defined in all patients and delineated using Live Wire tools. The SAT and VAT components of chest were then segmented guided by this interface. The SAS approach was used to identify the corresponding anatomic slices in each chest CT study, and SAT and VAT areas in each slice as well as their whole volumes were quantified. Similarly, the SAT and VAT components were segmented in the abdomen and thigh slices. Key parameters of the attenuation (Hounsfield unit (HU) distributions) were determined from each chest slice and from the whole chest volume separately for SAT and VAT components. The same parameters were also computed from the single abdominal and thigh slices. The ability of the slice at each anatomic location in the chest (and abdomen and thigh) to act as a marker of the measures derived from the whole chest volume was assessed via Pearson correlation coefficient (PCC) analysis.

          Results

          The SAS approach correctly identified slice locations in different subjects in terms of vertebral levels. PCC between chest fat volume and chest slice fat area was maximal at the T8 level for SAT (0.97) and at the T7 level for VAT (0.86), and was modest between chest fat volume and abdominal slice fat area for SAT and VAT (0.73 and 0.75, respectively). However, correlation was weak for chest fat volume and thigh slice fat area for SAT and VAT (0.52 and 0.37, respectively), and for chest fat volume for SAT and VAT and BMI (0.65 and 0.28, respectively). These same single slice locations with maximal PCC were found for SAT and VAT within both COPD and IPF groups. Most of the attenuation properties derived from the whole chest volume and single best chest slice for VAT (but not for SAT) were significantly different between COPD and IPF groups.

          Conclusions

          This study demonstrates a new way of optimally selecting slices whose measurements may be used as markers of similar measurements made on the whole chest volume. The results suggest that one or two slices imaged at T7 and T8 vertebral levels may be enough to estimate reliably the total SAT and VAT components of chest fat and the quality of chest fat as determined by attenuation distributions in the entire chest volume.

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          Most cited references37

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          Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study.

          Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome (P range < 0.01). In women, relations between VAT and risk factors were consistently stronger than in men. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. For example, among women and men, both SAT and VAT were associated with increased odds of metabolic syndrome. In women, the odds ratio (OR) of metabolic syndrome per 1-standard deviation increase in VAT (OR, 4.7) was stronger than that for SAT (OR, 3.0; P for difference between SAT and VAT < 0.0001); similar differences were noted for men (OR for VAT, 4.2; OR for SAT, 2.5). Furthermore, VAT but not SAT contributed significantly to risk factor variation after adjustment for body mass index and waist circumference (P < or = 0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively. Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
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            Human epicardial adipose tissue is a source of inflammatory mediators.

            Inflammatory mediators that originate in vascular and extravascular tissues promote coronary lesion formation. Adipose tissue may function as an endocrine organ that contributes to an inflammatory burden in patients at risk of cardiovascular complications. In this study, we sought to compare expression of inflammatory mediators in epicardial and subcutaneous adipose stores in patients with critical CAD. Paired samples of epicardial and subcutaneous adipose tissues were harvested at the outset of elective CABG surgery (n=42; age 65+/-10 years). Local expression of chemokine (monocyte chemotactic protein [MCP]-1) and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) was analyzed by TaqMan real-time reverse transcription-polymerase chain reaction (mRNA) and by ELISA (protein release over 3 hours). Significantly higher levels of IL-1beta, IL-6, MCP-1, and TNF-alpha mRNA and protein were observed in epicardial adipose stores. Proinflammatory properties of epicardial adipose tissue were noted irrespective of clinical variables (diabetes, body mass index, and chronic use of statins or ACE inhibitors/angiotensin II receptor blockers) or plasma concentrations of circulating biomarkers. In a subset of samples (n=11), global gene expression was explored by DNA microarray hybridization and confirmed the presence of a broad inflammatory reaction in epicardial adipose tissue in patients with coronary artery disease. The above findings were paralleled by the presence of inflammatory cell infiltrates in epicardial adipose stores. Epicardial adipose tissue is a source of several inflammatory mediators in high-risk cardiac patients. Plasma inflammatory biomarkers may not adequately reflect local tissue inflammation. Current therapies do not appear to eliminate local inflammatory signals in epicardial adipose tissue.
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              Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study.

              Pericardial fat may be an important mediator of metabolic risk. Correlations with cardiovascular disease risk factors and vascular calcification in a community-based sample are lacking. We sought to examine associations between pericardial fat, metabolic risk factors, and vascular calcification. Participants free of cardiovascular disease from the Framingham Heart Study (n=1155, mean age 63 years, 54.8% women) who were part of a multidetector computed tomography study underwent quantification of intrathoracic fat, pericardial fat, visceral abdominal fat (VAT), coronary artery calcification, and aortic artery calcification. Intrathoracic and pericardial fat volumes were examined in relation to body mass index, waist circumference, VAT, metabolic risk factors, coronary artery calcification, and abdominal aortic calcification. Intrathoracic and pericardial fat were directly correlated with body mass index (r=0.41 to 0.51, P 0.05). Pericardial fat, but not intrathoracic fat, was associated with coronary artery calcification after multivariable and VAT adjustment (odds ratio 1.21, 95% confidence interval 1.005 to 1.46, P=0.04), whereas intrathoracic fat, but not pericardial fat, was associated with abdominal aortic calcification (odds ratio 1.32, 95% confidence interval 1.03 to 1.67, P=0.03). Pericardial fat is correlated with multiple measures of adiposity and cardiovascular disease risk factors, but VAT is a stronger correlate of most metabolic risk factors. However, intrathoracic and pericardial fat are associated with vascular calcification, which suggests that these fat depots may exert local toxic effects on the vasculature.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 January 2017
                2017
                : 12
                : 1
                : e0168932
                Affiliations
                [1 ]Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [2 ]Department of Medicine, Duke University, Durham, North Carolina, United States of America
                [3 ]Department of Radiology, Columbia University, New York City, New York, United States of America
                [4 ]Department of Radiology, University of Iowa, Iowa City, Iowa, United States of America
                [5 ]Division of Pulmonary and Critical Care Medicine, Hospital of the University of Pennsylvania & Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
                [6 ]Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York City, New York, United States of America
                University of Chicago, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: JU YT DT.

                • Data curation: YT DO MS JC DL.

                • Formal analysis: JU YT DT JC DL.

                • Funding acquisition: JC DL.

                • Investigation: JU JC DL.

                • Methodology: JU YT DT.

                • Project administration: JU JC DL.

                • Resources: SP AR MS JN MP JD JC DL.

                • Software: YT DO.

                • Supervision: JU DT JC DL.

                • Validation: YT JU DT CW GP JC DL.

                • Visualization: YT JU.

                • Writing – original draft: YT JU.

                • Writing – review & editing: DT JC DL.

                Article
                PONE-D-16-24626
                10.1371/journal.pone.0168932
                5207652
                28046024
                9cd6996c-fd13-4731-8043-38f9327565b8
                © 2017 Tong et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2016
                : 8 December 2016
                Page count
                Figures: 5, Tables: 6, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 HL114626
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 HL087115
                Award Recipient :
                This research is partly funded by the National Institutes of Health (NIH) DHHS grant R01 HL114626 (to Lederer and Christie), R01 HL087115 (to Christie), K24 HL115354 (to Christie), and K24 HL131937 (to Lederer) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fats
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Computed Axial Tomography
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Computed Axial Tomography
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Tomography
                Computed Axial Tomography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Tomography
                Computed Axial Tomography
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Tomography
                Computed Axial Tomography
                Medicine and Health Sciences
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Biology and Life Sciences
                Anatomy
                Thorax
                Medicine and Health Sciences
                Anatomy
                Thorax
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Lung Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Respiratory System Procedures
                Lung Transplantation
                Biology and Life Sciences
                Anatomy
                Abdomen
                Medicine and Health Sciences
                Anatomy
                Abdomen
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                Medicine and Health Sciences
                Anatomy
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                Custom metadata
                All LTBC analysis data files are available from Figshare with DOI information as follows: Tong, Yubing (2016): Chest fat quantification via CT based on standardized anatomy space in adult lung transplant candidates. figshare: https://dx.doi.org/10.6084/m9.figshare.4325804.v1.

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