Heart failure is the cause of 270,000 deaths in the U.S. and 3.4 million annual hospital visits. The risk-adjusted 1-year mortality of heart failure ha remained essentially unchanged between 1999 (31.7%) and 2008 (29.6%), despite a significant decrease in mortality associated with acute myocardial infarction (10.7% per year for men). Recent attempts to prevent post-infarction heart failure through novel pharmacologic, stem cell, and mechanical therapies have shown promise in animal studies but subsequent studies in patients showed very limited success. This can be partly attributed to the lack of high spatial resolution methods to evaluate the consequences of infarction and subsequent therapy on regional contractile function and myocardial health. Current gold-standard approaches to determine contractile function include pressure-volume loops and strain measurement via MRI. Although MRI can image LV function and strain with high spatial resolution, it is a multi- shot, multiple heartbeat acquisition that is too slow to measure beat-to-beat changes in myocardial work. The goal of this project is to develop real-time MRI methods to measure regional myocardial work density and Frank-Starling relations during infarct development and validate these results with conventional MRI and biochemistry in a porcine model. To achieve this goal, (1) the rt-MRI approach will be improved and optimized. Compressed sensing will further improve the current sub-Nyquist image reconstruction algorithm we have implemented. In addition, modification of the k-space sampling trajectory will improve artifact incoherence and algorithm performance. Then, (2) validation of regional estimates of myocardial function will be performed. The proposed method tracks myocardial wall thickening and regional work density and Frank-Starling relations. SPAMM-tagged images and conventional CINE imaging of ventricular motion will be used to generate comparable values. Finally, (3) an initial serial infart swine study will be used to correlate observed rt-MRI based changes in function to histological testing. This will determine the spatial resolution and temporal accuracy of the proposed method. The proposal develops a method to allow for in-vivo and longitudinal evaluation of post-infarction ventricular remodeling. Such a method is necessary for advanced design and evaluation of novel therapies for prevention of infarct-induced heart failure.

Public Health Relevance

Heart failure is the cause of 270,000 deaths in the U.S. with 3.4 million annual hospital visits and mortality which has remained essentially unchanged between 1999 (31.7%) and 2008 (29.6%), despite a significant decrease in acute myocardial infarction associated mortality (10.7% per year for men) Recent attempts to prevent heart failure in patients through pharmacologic, stem cell, and mechanical therapies have shown limited success partly because of our inability to evaluate the regional consequences of infarction and subsequent therapy. The goal of this project is to develop real-time MRI methods to measure changes in regional myocardial function during infarct development. We propose to validate these results with conventional MRI-based measures as well as histology in a pilot post-infarct swine study.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31HL120580-01A1
Application #
8721102
Study Section
Special Emphasis Panel (ZRG1-F15-P (20))
Program Officer
Meadows, Tawanna
Project Start
2014-07-01
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$45,156
Indirect Cost
Name
University of Pennsylvania
Department
None
Type
Schools of Engineering
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104