The ongoing projects at the Molecular Biomedical Imaging Laboratory include: 1) Noninvasive Imaging of Heart Failure (10-CC-0153, NCT01160471, PI: Dr. Bluemke). Heart failure is a common cardiovascular disorder in the elderly. Its incidence increases with age, affecting up to 10% of people old than 65 years. 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 study 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. We are planning to enroll 160 heart failure patients and 32 normal volunteers for this study. Significant progress has been made in quantifying diffuse myocardial fibrosis using CMR and MDCT extracellular volume fraction (ECV) technique. On patent application was filed on the novel CT whole heart ECV technique (Application No. 61/648,996). 2) Randomized Trial of Imaging versus Risk Factor Based Therapy for Plaque Regression (10-CC-0208, NCT01212900, PI: Dr. Bluemke) 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 moderate 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 achieving that target. 3) 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. MESA exam 5 was the first large-scale study in which delayed enhancement CMR imaging was used. 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. 4) Cardiac MRI core lab of HCM Net 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 HCMNet Study is a NHLBI funded multicenter 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. 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. 5) 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. Regression of cardiac hypertrophy is expected to improve morbidity and decrease the risk of SCD in HCM, as observed upon regression of load-dependent cardiac hypertrophy. 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. 6) Technical development of MRI-PET (10-CC-0115, NCT01130545, PI: Dr. Bluemke) The overall goal of this project is to determine the feasibility of integrated human MRI-PET with data acquired from both MRI and PET in a simultaneous fashion. PET-CT is widely used for oncologic applications. Some limitations of PET-CT are the additional radiation exposure from the CT scan, as well as the lack of soft tissue characterization by CT scanning. In addition, no motion compensation technique is currently available for CT scanning. Our initial studies have focused on lesion detection using the MRI-PET scanner in comparison to the conventional equipment. In order to improve the quality of the MRI-PET scanner, our efforts are focusing on methods to improve image registration between the MRI and PET data. There are two approaches being explored. The first is to modify pulse sequences to allow continuous motion tracking, thus allowing motion compensation and improved registration with the PET data. The second is to use PET projection data to improve the reconstruction accuracy by evaluating the motion path of the PET signal. One or both methods will be necessary for our applications that will eventually be targeted on obtaining vascular and myocardial simultaneous MRI/PET data using FDG as a tracer. 7) Development of specific collagen probe for myocardial fibrosis. Fibrosis is characterized by abnormal accumulation of collagen. Both the CMR and MDCT techniques are indirectly related to the extent of myocardial collagen by measuring the expansion of myocardial interstitial space. For cardiovascular imaging, a PET labeled collagen probe should provide superior contrast to noise ratio and the potential for quantification of signal. In this proposal, we seek to validate a more specific and direct molecular probe for myocardial collagen detection using PET imaging.
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