Goals and Objectives: The research of the Molecular Biomedical Imaging Laboratory (MBIL) includes developing patient-based methods for detection and quantitative characterization of subclinical cardiovascular disease of the myocardium and blood vessels in both early phase clinical trials as well as in multi-center studies. Areas of study include genetically determined disease, as well as acquired cardiovascular disease as a result of common risk factors. Methods include advanced magnetic resonance techniques, cardiovascular computed tomography, and positron emission tomography. The ongoing projects include: 1) Epidemiology of Diabetes Interventions and Complications (EDIC) (10-CC-N010) The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study is to provide data on the benefits and effects of treatments and glucose lowering levels on the systemic complications seen in the Type 1 Diabetes Mellitus (T1DM) population. The NIDDK further expanded the study for an additional time to look at the cardiovascular disease, long-term microvascular, and neuropathic issues that are seen in the T1DM population. MBIL and Johns Hopkins Hospital is working as the joined core CMR lab of this study. MBIL is evaluating the relationship between cardiovascular disease and risk factors using CMR. 2) Non-invasive Assessment of Atherosclerosis in Patients with Disorders of the Immune System (10-I-0029, NCT01063309, PI: Dr. John Gallin) Atherosclerosis, the major cause of heart disease, is thought to relate to dysregulated inflammation in the cardiac blood vessels and possibly results from over production of reactive oxygen species (ROS). The rate of atherosclerosis in patients with disorders of the immune system has not been well characterized but is likely to be dramatically different than that seen in the general population. Specifically, patients with Chronic Granulomatous Disease (CGD) may be protected from developing atherosclerosis due to reduced superoxide and other ROS production by phagocytic cells. We hypothesize that patients with CGD are at decreased risk of developing atherosclerosis. The primary objective will be assessed using imaging techniques to measure coronary artery calcium scores and the presence of absence of soft plaque. Participants undergo prospective CT angiography, gadolinium enhanced cardiac MR and high resolution carotid MR imaging. 3) Cardiometabolic Assessment in HIV (NCT01089114, PI: Dr. Colleen Hadigan) HIV is now a chronic infection as patients with access to antiretroviral therapy have significantly improved life expectancies. Patients with HIV also have an increased risk of cardiovascular disease. Thus, cardiovascular disease is an important potential co-morbidity for patients living with HIV. The study will perform a detailed cardiovascular assessment using state-of-the-art imaging techniques to evaluate intramyocardial lipid as well as coronary artery disease and myocardial function in a cohort of 100 HIV infected patients and 30 healthy volunteers as controls. The MBIL is collaborating with NIAID researchers quantify intramyocaridial, intrahepatic and intramyocellular triglyceride content with MRI spectroscopy and the anatomy and function of heart using Cardiac CT and MRI. 5) Multi-Ethnic Study of Atherosclerosis (MESA, NCT00005487, PI: Dr. Bluemke) The Multi-Ethnic Study of Atherosclerosis (MESA) is an NHLBI funded study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and risk factors that predict progression to clinically overt cardiovascular disease, and that predict progression of subclinical disease itself, in a diverse, population-based sample of 6,500 men and women aged 45-84. MBIL and Johns Hopkins Hospital have been working as a joint core CMR lab for this study for MESA exam 5. MBIL was actively involved in the protocol design, staff training, database design and implementation, and image analysis of MESA exam 5. MBIL has finished reading of more than 3000 cases. 6) Evaluation and optimization of myocardial mechanics and tissue composition a) Cardiac MRI core lab of HCM Net Study; Cardiac MRI core lab of Vanish study (OHSR-CC-5125, PI: Dr. Carolyn Ho) Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular genetic disorder, marked by phenotypic and genotypic heterogeneity. The MBIL is the core cardiac MRI lab of the HCMNet study. MBIL has finished the reading of all cases of the first phase of this study and will continue work on the second phase of this study, which would be a medical treatment study of HCM. The VANISH study is phase 2 of this project, with MBIL delivery core laboratory training and establishing the cardiac magnetic resonance protocol for this multi-center study. c) Cardiac MRI core lab of Halt HCM Study (OHSR-CC-11322, NCT01537926, PI: Dr. Ali Marian) Regression of Hypertrophy with N-acetylcysteine (NAC) in Hypertrophic Cardiomyopathy (HALT-HCM) is a NHLBI funded study. Despite HCMs clinical impact, there is no effective pharmacological therapy for HCM. None of the current pharmacological therapies reverses or attenuates cardiac hypertrophy or reduces the risk of SCD in adults. Cardiac hypertrophy, the essential clinical feature of human HCM, is a major determinant of morbidity and the risk of SCD. The primary objective is to perform a pilot study in HCM patients with gene mutations to assess safety and gather the pre-requisite data for subsequent robust randomized placebo-controlled efficacy studies with NAC. The MBIL is the core cardiac MRI lab of the Halt-HCM study. The study has enrolled a limited number of subjects to date, and the cardiac magnetic resonance studies from these subjects will be evaluated by MBIL. d) Cardiac MRI core lab of Genetics, mechanisms and clinical phenotypes of arrhythmogenic cardiomyopathy (NCT: pending. PI: Jeffrey Towbin) Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a common cause of sudden cardiac death in young people.
The specific aims i nclude 1: To identify new genes causing ARVC, ALVC, and aDCM, 2A: To evaluate genotype-phenotype associations in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC); MBIL is the core lab of this study which is currently in the start-up phase with establishment of the CMR protocol, forms and procedures to be submitted to field centers. 7) The Psoriasis, Atherosclerosis, and Cardiometabolic Disease Initiative (PACI) (PI Mehta, NCT NCT01778569) Psoriasis is an inflammation that mostly affects the skin but can affect the entire body. Another disorder, atherosclerosis, is a process in which cholesterol is gradually deposited on the wall of arteries. Many cells that cause psoriasis also cause atherosclerosis. The purpose of this study is to study the relationship between psoriasis and cardiometabolic diseases.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACL090019-08
Application #
9568237
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
Zip Code
Symons, Rolf; Pourmorteza, Amir; Sandfort, Veit et al. (2017) Feasibility of Dose-reduced Chest CT with Photon-counting Detectors: Initial Results in Humans. Radiology 285:980-989
Symons, Rolf; Krauss, Bernhard; Sahbaee, Pooyan et al. (2017) Photon-counting CT for simultaneous imaging of multiple contrast agents in the abdomen: An in vivo study. Med Phys 44:5120-5127
Symons, Rolf; Cork, Tyler E; Sahbaee, Pooyan et al. (2017) Low-dose lung cancer screening with photon-counting CT: a feasibility study. Phys Med Biol 62:202-213
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Bluemke, David A; Kawel-Boehm, Nadine (2016) Can a MR Imaging Scanner Accurately Measure Hematocrit to Determine ECV Fraction? JACC Cardiovasc Imaging 9:64-6
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Pourmorteza, Amir; Symons, Rolf; Sandfort, Veit et al. (2016) Abdominal Imaging with Contrast-enhanced Photon-counting CT: First Human Experience. Radiology 279:239-45
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