Molecular Biomedical Imaging Laboratory

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The ongoing projects at the The Molecular Biomedical Imaging Laboratory (MBIL) include: 1) Noninvasive Imaging of Heart Failure (10-CC-0153). Heart failure is a common cardiovascular disorder in the elderly. Its incidence increases with age, affecting up to 10% of people > 65 years of age. In the US, heart failure is one of the most common diagnoses at discharge among medicare beneficiaries. A recent estimate suggested that the total cost of heart failure related care in the US could be as high as $27.9 billion. Projection into the middle part of this century suggests that, as the population ages, the prevalence and cost of heart failure will continue to rise. The primary aim of this proposal is to investigate noninvasive imaging methods for quantifying diffuse myocardial fibrosis with cardiac magnetic resonance imaging (CMR) and multi-detector computed tomography (MDCT) in heart failure patients. Myocardial fibrosis plays an essential role in the development and progression of heart failure. Excess deposition of collagen in extracellular matrix can lead to increased myocardial stiffness and subsequently to cardiac hypertrophy and left ventricular dysfunction. So far there is no non-invasive method to quantify diffuse fibrosis, and we are trying to solve this problem. This is a two year natural history study. We are planning to enroll 160 heart failure patients and 32 normal volunteers for this study. During the last fiscal year, 15 heart failure patients and 10 normal volunteers have been enrolled in this study. Staff has established the MRI ECV reference value at 3T and validated that cardiac CT ECV is correlated to MRI ECV. 2) Cardiac MRI core lab of HCMNet Study (OHSR-CC-5125) Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular genetic disorder, marked by phenotypic and genotypic heterogeneity. The HCMNet Study is an NHLBI funded multicenter observational study focused on the comprehensive characterization of preclinical HCM, overt HCM (G+/LVH+= positive control population), and normal controls (G-/LVH-) in order to identify reliable phenotypes of early disease development and potential surrogate endpoints to monitor treatment response. The aim of the study is to establish the prerequisites for effective translation of basic discoveries to anticipated future human clinical trials to prevent or modify the development of HCM. The MBIL is the core cardiac MRI lab of the HCMNet study. In the preparation phase, MBIL designed advanced cardiac protocol including cine image, tagging, delayed enhancement and T1 mapping, validated research sequences, coordinated research sequence distribution, established the CMR database and trained MRI technicians. Currently, 42 subjects have been enrolled in the study and the MBIL is analyzing CMR data. 3) Randomized Trial of Imaging Versus Risk Factor Based Therapy for Plaque Regression (10-CC-0208) The overall aim of this study is to compare the effectiveness of an image guided approach to lipid lowering to standard therapy guided by clinical risk factors and blood lipid levels. Men and women over age 55 who are candidates for statin therapy will be randomized to usual cholesterol lowering care, or to care guided by MRI images of the carotid arteries. Participants randomized to the second, imaging guided, group will be assigned to LDL cholesterol targets according to the degree of atherosclerosis seen by MRI. The study endpoints will be the total degree of plaque regression seen, the dosage of statin drugs required to achieve that reduction, and the rate of cardiovascular events. FDG-PET is hypothesized to enable visualization of anti-inflammatory effects of statins that most likely occur before anatomic regression of the plaques can be demonstrated on MRI. A pilot substudy is to be conducted to explore this relationship. A subgroup of patients will be selected based on a moderrate or high degree of atherosclerosis on carotid MRI and asked to participate in FDG PET imaging. The purpose of this pilot study is to determine if FDG avid lesions undergo a greater degree of morphologic regression with therapy controlling for the reduction in LDL cholesterol and the dosage of statins required to achieve that target. 40 subjects have been enrolled in this study. 4) Multi-Ethnic Study of Atherosclerosis (MESA) 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. Approximately 40 percent of the cohort will be white, 30 percent African-American, 20 percent Hispanic, and 10 percent Asian, predominantly of Chinese descent. MBIL and Johns Hopkins Hospital have been working as a joint core CMR lab for this study since MESA5. MESA5 was the first large-scale study in which delayed enhancement imaging was used. MBIL was actively involved in the protocol design, staff training, database design and implementation, and image analysis of MESA5.