Molecular Biomedical Imaging Laboratory (CC)

Clinical Center

Investigators

Linked publications & trials

Abstract

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) Breast Cancer Imaging Breast cancer is the most common cancer among women and the second most common cause of death. X-ray mammography is the standard screening tool for breast cancer with its unique ability of detecting micro-calcification which is a strong early predictor of ductal carcinoma in situ (DCIS). DCIS was recently reported to account for 20-30% of detected breast cancers. When DCIS is early detected and completely excised, 100% cure rate is achieved. Yet, recent reports have shown that MRI carries higher sensitivity in detecting DCIS than does x-ray mammography. DCIS appears in MRI mostly as ductal or segmental non mass like enhancement (NMLE). Correlation between micro-calcifications detected on mammogram and enhancing lesions detected by MRI is essential. Also, invasive lobular carcinoma (ILC), which is the second most common invasive cancer of the breast is another challenge for x-ray mammography and is considered the most important cause of false negative rates of x-ray mammography. Again, MRI carries higher sensitivity in detecting ILC with the documented lowest false negative rates. Various newer MRI techniques are used in attempt to improve the specificity of the test. These MRI techniques involve dynamic imaging, diffusion imaging and spectroscopy. 3) The Treatment of Stage I and II Carcinoma of the Breast with Mastectomy and Axillary Dissection vs. Excisional Biopsy, Axillary Dissection, and Definitive Irradiation (79-C-0111, NCT00026845, PI: Dr. Nicole Simone) Radiation exposure to the heart in the course of cancer therapy is known to predispose to atherosclerosis, myocardial fibrosis and pericardial disease. Whether this risk is significant in the setting of tangentially applied radiotherapy for treatment of breast cancer is less clear. 49 women with a history of stage I and II breast carcinoma underwent cardiac MRI and coronary CT angiography for the non-invasive evaluation of atherosclerotic and pericardial disease. This study is closed and MBIL lab is analyzing data and prepares manuscript. 4) Acute stress cardiomyopathy project (NIH Bench to Bed Award, PI: Dr. Christopher Sibley) Acute stress cardiomyopathy is a recently recognized syndrome of profound but reversible ventricular dysfunction occurring in the setting of emotional, physical or pharmacologic stress. Original reports focused on a subset marked by a distinctive pattern of apical akinesis and basal hypercontractility referred to as apical ballooning or tako-tsubo syndrome. While the short term prognosis of acute stress cardiomyopathy is excellent, little is known about the long term sequence of the syndrome beyond 4 years. This proposal will evaluate the general hypothesis that abnormalities of cardiac sympathetic function result in the regional dysfunction and myocardial injury observed in stress cardiomyopathy. Myocardial PET imaging using radiolabelled epinephrine is the most powerful noninvasive means to assess the integrity of cardiac sympathetic function, reflecting neuronal uptake, storage and release. 5) 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 of this study is to determine the prevalence of atherosclerosis in these and other patients with in-born disorders of immune function. The primary objective will be assessed using imaging techniques to measure coronary artery calcium scores and the presence of absence of soft plaque. Secondary endpoints include physiologic characteristics such as blood pressure as well as circulating biomarkers associated with heart disease such as C-reactive protein and lipid profile. This study may lead to improved understanding of the pathophysiology of atherosclerosis and could lead to novel therapies for atherosclerosis that may benefit patients with immune disorders and the general population. Participants undergo prospective CT angiography, gadolinium enhanced cardiac MR and high resolution carotid MR imaging. 6) 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. This is an early exploratory cross-sectional study designed to both assess the burden of disease and apply novel techniques in a uniquely at-risk population. 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. 7) ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study (NCT00410241, PI, Dr. Leslie Biesecker) We propose to study the utility of whole exome sequence prediction on the extent of coronary artery atherosclerosis identified by coronary artery CT angiography. For this pilot study, we evaluated rare variants in genes located in the linkage disequilibrium regions of index SNPs identified by genome-wide association studies (GWAS) of CAD. It was felt that looking at rare variants in genes genetically linked to these index SNPs would add mechanistic information to the current GWAS findings. Groups of patients with rare variants in these genes were compared to the rest of the ClinSeq cohort for whom whole exome sequencing is available (572 patients). Based on this analysis, 11 patients with rare variants in SORT1 showed significance difference with respect to CAC when compared to the rest of the cohorts. SORT1 has recently been implicated in the pathophysiology of CAD and lipid metabolism by means of GWAS.