Multi-Modality and Molecular Imaging of Post-MI Remodeling

Department of Biomedical Engineering Seminar Series

"Multi-Modality and Molecular Imaging of Post-MI Remodeling"

Albert J. Sinusas, MD
Professor of Medicine and Diagnostic Radiology
Director Yale Translational Research Imaging Center
Yale University School of Medicine

Abstract: Targeted molecular imaging has already started to play a role in clinical cardiovascular medicine. The lower sensitivity of ultrasound or MR-based molecular imaging approaches has limited their clinical translation. SPECT and PET imaging approaches provide high sensitivity, relatively low cost, and a minimal potential for adverse biological effects, and therefore provide the quickest means for translation of molecular imaging to patient care. However, the limited resolution of nuclear imaging requires anatomical co-localization of nuclear images with higher resolution anatomical X-ray CT or MR images.
Changes in the structure, geometry and eventually function of the left ventricle (LV) occur following myocardial infarction (MI) and has been termed post-MI remodeling. The process of post-MI myocardial LV remodeling often leads to heart failure and is associated with important changes within the myocardial extracellular matrix (ECM). The matrix metalloproteinases (MMPs) constitute a large family of proteolytic enzymes responsible for ECM degradation and remodeling under normal and pathological conditions. A clear cause/effect relationship between MMPs and the LV remodeling process has been demonstrated through the use of animal models of developing congestive heart failure, transgenic models, as well as through the use of pharmacological MMP inhibition studies. However, a non-invasive method for detecting and quantifying MMP activity in-vivo during the evolution of post-MI remodeling has yet to be developed and forms a critical component for translating these basic observations to clinical applicability. We have combined high sensitivity MMP targeted molecular imaging approaches and cine magnetic resonance (MR) and ultrasound imaging methods in order to quantify regional MMP activity and changes in LV deformation and geometry post-MI. The studies to be discussed employ multi-modality SPECT/CT and MR imaging and established murine and porcine models of post-MI remodeling, to relate temporal changes in regional MMP activation with changes in regional myocardial deformation. These approaches have been used to evaluate novel polymer-based therapies in the heart. The targeted molecular imaging approach that will be discussed have provided insights into the role of mechanical forces and MMP activation in the processes involved in ventricular remodeling, and may translate to direct clinical applications that hold both prognostic and diagnostic potential. Molecular imaging of the cardiovascular system will enhance the development and application of truly personalized therapeutic regimens, and facilitate the monitoring of therapeutic efficacy and outcome.

When: Thursday, February 5th, 2015
Place: 10 Amistad Room 112
Time: 4PM