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3266 Understanding epicardial adipose biology by imaging, transcriptomic, and lipidomic profiling
- Jadranka Stojanovska, Alex Tsodikov, Carey Lumeng, Charles Burant, Thomas Chenevert
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 157-158
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OBJECTIVES/SPECIFIC AIMS: The study aims to understand if pro inflammatory epicardial white adipose phenotype is positively associated with coronary atherosclerosis, while the brown adipose phenotype is negatively associated. Primary outcome is association between epicardial fat fraction and coronary atherosclerosis and cardiac function. Secondary outcome is transcriptomic and lipidomic profiling between epicardial, extra pericardial, and subcutaneous depots and how these profiles correlate with fat fraction. METHODS/STUDY POPULATION: Recruited patients undergoing open-heart surgery provided informed consent at their second visit and underwent laboratory testing and imaging (cardiac magnetic resonance including water-fat imaging and coronary calcium computed tomography) prior to their surgery. Cardiac function such as cardiac chamber volume, mass, function, and strain, and depo-specific fat fraction were calculated from cardiac MR and Agatston calcium score and epicardial adipose volume from CT images. At the time of surgery, a tissue specimens from the epicardial, extrapericardial, and subcutaneous depots were obtained for transcriptomic and lipidomic analysis. Linear and logistic regression analyses adjusted for other variables were performed to evaluate significance level between variables. RESULTS/ANTICIPATED RESULTS: 37 subjects were enrolled in the study, 13 (35%) of which were women. Cardiac function and fat fraction was quantified in all patients, whereas tissue analyses were performed in 22 patients. Epicardial and extrapericardial fat fraction were independently associated with coronary atherosclerosis (p-value 0.01 and 0.04 respectively) Only epicardial fat fraction was negatively associated with global circumferential shortening of the left ventricle (0.03), while neither the extrapericardial fat fraction nor epicardial adipose volume were not (p =0.33 and 0.97 respectively) All three adipose depots have unique gene signatures with differentially expressed genes and pathways. RNA sequencing of epicardial, extrapericardial, and subcutaneous depots demonstrated tight clustering of epicardial and subcutaneous signatures based on PCA analysis (Figure 2). 19 lipid classes and 59 lipids showed differential expression between at least 2 of the fat depots (Figure 3). Hierarchal clustering of the lipids showed that epicardial and extrapericardial depots were more closely related than subcutaneous adipose. Plasmenyl-phosphatidylcholines, with an ether-linked fatty acid at the sn-1 position of the lipid, were higher in subcutaneous fat while most other lipids were higher in epicardial fat per tissue weight, such as ceramides (p=0.002). DISCUSSION/SIGNIFICANCE OF IMPACT: Epicardial, extrapericardial, and subcutaneous adipose depots express different lipidome and transcriptome signatures and different pathways. GSEA analysis demonstrated enrichment of genes related to antigen presentation and B cell immunity in epicardial compared to subcutaneous adipose tissue. Epicardial fat fraction is associated with coronary atherosclerosis and decreased left ventricular global circumferential shortening as an early predictor of decreased left ventricular stroke volume. Epicardial fat fraction is also associated with cermides which may play role in the development of coronary atherosclerosis and decreased cardiac function.
2370: Understanding epicardial fat biology by imaging
- Jadranka Stojanovska, Thomas Chenevert, Alex Tsodikov, Carey Lumeng, Charles Burant
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, p. 63
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OBJECTIVES/SPECIFIC AIMS: The goal is to understand the underlying mechanism of epicaridial fat biology and its response to cardiometabolic disease by using quantitative multi-echo Dixon (mDixon) of water and lipid sequence, T2* blood-oxygen-level-dependent (BOLD) sequence of iron content, and data analysis methods to determine the quantity of brown Versus white fat. To accomplish this goal, we propose to define the histological, genetic, and metabolite state of epicardial fat and to confirm the relationship between fat phenotype and magnetic resonance (MR) characteristics. We will then investigate whether MR is more effective in identifying patients with lower cardiovascular disease risk than computed tomography (CT). METHODS/STUDY POPULATION: We will recruit 100 patients undergoing open-heart surgery and will quantify mDixon (proton density fat fraction), BOLD (T2*), and T2/T1 maps of epicardial, extrapericardial, and subcutaneous fat before their surgery. We will then (a) validate MR findings by direct depot-specific tissue analysis for lipid content, histological, and genetic markers of inflammation and brown and white fat, (b) develop plasma and fat depot specific metabolite profiling of cardiovascular disease risk and correlate with imaging characteristics. We will categorize cardiovascular risk score (Cardiovascular Health Status) of our 100 patients on quartiles. We will then build models where the categorized cardiovascular risk score are regressed on MR measures (epicardial fat fraction, T2*, and T2/T1 maps) and CT measures (epicardial fat volume and coronary calcium score). RESULTS/ANTICIPATED RESULTS: We anticipate to learn about epicardial fat biology and the role of inflammation in cardiometabolic disease. We will validate proton density fat fraction, T2* and T2 map against histology of epicardial fat for lipid content, established markers of brown and white fat and inflammation, respectively, to help us translate imaging technique to clinical practice. In respect to our second aim we anticipate that MR identifies patients at lower cardiovascular risk quartile than CT. DISCUSSION/SIGNIFICANCE OF IMPACT: Interest in epicardial fat as a visceral fat of the heart and coronary arteries is rapidly growing as the scientific based evidence indicates that the anatomic specificity is an important contributor to the cardiovascular diseases. The transformation of epicardial fat from a cardioprotective phenotype to a pro-inflammatory, atherosclerosis-promoting state triggers inflammation that is coincident with the expansion of epicardial fat volume detected by anatomic imaging. This study will impact the management of patients at risk for cardiovascular disease because it will demonstrate that quantification of epicardial fat status by MR identifies fat tissue changes validated by histology at lower cardiovascular disease risk quartile than CT.
Chapter 23 - Diffusion MR imaging in adult neoplasia
- from Section 3 - Adult neoplasia
- Edited by Jonathan H. Gillard, University of Cambridge, Adam D. Waldman, Imperial College London, Peter B. Barker, The Johns Hopkins University School of Medicine
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- Clinical MR Neuroimaging
- Published online:
- 05 March 2013
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- 26 November 2009, pp 321-340
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Summary
Introduction
Diffusion-weighted MRI (DWI) is increasingly being incorporated into standard clinical evaluation of brain tumors. Driven by compelling results from experimental animal models, an increasing number of clinical research groups have begun to evaluate the potential of DWI to improve clinical management of brain tumors. The principles of DWI are covered in Ch. 4. This chapter contains an overview of the current developments in DWI as applied to adult neuro-oncology. Specific examples have been drawn from the literature to demonstrate how DWI can provide unique and valuable information with regard to diagnosis, treatment planning, and therapeutic monitoring of brain neoplasia (Table 23.1).
The current clinical value of conventional MRI resides in its ability to demonstrate gross tumor morphology and temporal changes non-invasively. Conventional MRI exploits a variety of tissue properties that allow the neuro-oncologist/neuroradiologist to assess gross tumor extent on the resultant contrasts, such as T2-weighted (Fig. 23.1), gadolinium (Gd)-enhanced T1-weighted and diffusion-weighted (Fig. 23.1) images. The typical radiological assessment is somewhat interpretive and based on the spatial extent and location of abnormal tissue contrast. The actual image contrast values are rarely quantified, as these are usually scaled arbitrarily and do not have a simple relationship to microscopic tissue properties. There is significant clinical potential for MR techniques that provide additional quantitative or semiquantitative functional, structural, or molecular information related to tumor biology and physiology. Such information may be derived from MR signals that reflect perfusion dynamics, oxygenation levels, biochemistry/metabolism, cellularity, and levels of gene expression.
20 - Diffusion MR imaging in adult neoplasia
- from SECTION 3 - ADULT NEOPLASIA
- Edited by Jonathan H. Gillard, University of Cambridge, Adam D. Waldman, Charing Cross Hospital, London, Peter B. Barker, The Johns Hopkins University
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- Book:
- Clinical MR Neuroimaging
- Published online:
- 07 December 2009
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- 02 December 2004, pp 312-328
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Environmental Contamination Due to Methicillin-Resistant Staphylococcus aureus: Possible Infection Control Implications
- John M. Boyce, Gail Potter-Bynoe, Claire Chenevert, Thomas King
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 18 / Issue 9 / September 1997
- Published online by Cambridge University Press:
- 02 January 2015, pp. 622-627
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- September 1997
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Objective:
To study the possible role of contaminated environmental surfaces as a reservoir of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals.
Design:A prospective culture survey of inanimate objects in the rooms of patients with MRSA.
Setting:A 200-bed university-affiliated teaching hospital.
Patients:Thirty-eight consecutive patients colonized or infected with MRSA. Patients represented endemic MRSA cases.
Results:Ninety-six (27%) of 350 surfaces sampled in the rooms of affected patients were contaminated with MRSA. When patients had MRSA in a wound or urine, 36% of surfaces were contaminated. In contrast, when MRSA was isolated from other body sites, only 6% of surfaces were contaminated (odds ratio, 8.8; 95% confidence interval, 3.725.5; Pく.0001). Environmental contamination occurred in the rooms of 73% of infected patients and 69% of colonized patients. Frequently contaminated objects included the floor, bed linens, the patient's gown, overbed tables, and blood pressure cuffs. Sixty-five percent of nurses who had performed morning patient-care activities on patients with MRSA in a wound or urine contaminated their nursing uniforms or gowns with MRSA. Forty-two percent of personnel who had no direct contact with such patients, but had touched contaminated surfaces, contaminated their gloves with MRSA.
Conclusions:We concluded that inanimate surfaces near affected patients commonly become contaminated with MRSA and that the frequency of contamination is affected by the body site at which patients are colonized or infected. That personnel may contaminate their gloves (or possibly their hands) by touching such surfaces suggests that contaminated environmental surfaces may serve as a reservoir of MRSA in hospitals.
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