The long-term goal of this proposed research project is to establish a high-resolution noninvasive 3- dimensional electrocardiographic imaging (3-DEIT) methodology that can noninvasively map cardiac electrical activity within the 3-dimensional (3-D) heart. Sudden death from ventricular tachycardia (VT) and ventricular fibrillation claims over 400,000 lives each year in the United States alone. Development of effective imaging technologies is critical in the evolution of interventional (and potentially pharmacologic) approaches to prevent and treat these malignant arrhythmias. Noninvasive mapping of activation sequence and localization of sites of origin of arrhythmia would thus be of enormous value for numerous patients. The ultimate goal of the proposed research project is to establish and validate a novel 3-D cardiac electrical imaging approach that has been pioneered by the PI which is able to image the activation sequence over the 3-D myocardium from noninvasive body surface potential maps. Although solving the cardiac inverse problem in 3-D translates into severe underdetermined nature in the inverse problem, the proposed use of a heart excitation model, in which cardiac electrophysiological knowledge is incorporated, will redefine this relationship. Also novel to the proposed research is rigorously validating the proposed 3- DEIT in a closed-chest animal model as assessed by 3-D intracardiac mapping. Our preliminary results in an animal model, that demonstrate reconstruction of activation sequence throughout the 3-D myocardium from noninvasive body surface potential measurements and computer tomography images (as tested with 3-D intracardiac mapping), attest to the feasibility of the proposed studies.
The specific aims of the proposed project are:
Aim 1) To develop 3-D electrocardiographic imaging methods and evaluate it in computer simulations;
Aim 2) To validate 3-D electrocardiographic imaging in vivo during ventricular pacing using 3-D intracardiac mapping in the rabbit heart;
and Aim 3) To validate 3-D electrocardiographic imaging during ventricular tachycardia in rabbits with experimentally-induced heart failure. The successful completion of the proposed research would enable us to establish a novel noninvasive cardiac functional imaging methodology that could define initiation sites, activation sequences (and potentially arrhythmogenic mechanisms) for pathologic arrhythmias (which is currently not possible). The results of this work would also provide the critical foundation for establishing the proposed 3-DEIT as a novel tomographic imaging modality to guide catheter ablation of arrhythmias, and to develop and to assess the effects of new therapeutic approaches targeted to specific arrhythmia mechanisms for the treatment of VT in patients with heart failure (and other cardiac diseases).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL080093-04
Application #
7866540
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Lathrop, David A
Project Start
2007-09-21
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$365,919
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Yang, Ting; Yu, Long; Jin, Qi et al. (2018) Localization of Origins of Premature Ventricular Contraction by Means of Convolutional Neural Network From 12-Lead ECG. IEEE Trans Biomed Eng 65:1662-1671
Cluitmans, Matthijs; Brooks, Dana H; MacLeod, Rob et al. (2018) Validation and Opportunities of Electrocardiographic Imaging: From Technical Achievements to Clinical Applications. Front Physiol 9:1305
Yu, Long; Jin, Qi; Zhou, Zhaoye et al. (2018) Three-Dimensional Noninvasive Imaging of Ventricular Arrhythmias in Patients With Premature Ventricular Contractions. IEEE Trans Biomed Eng 65:1495-1503
Long Yu; Pogwizd, Steven; Bin He (2016) Non-invasive imaging of ventricular activation during pacing and arrhythmia: Methods and validation. Conf Proc IEEE Eng Med Biol Soc 2016:113-116
Zhou, Zhaoye; Jin, Qi; Yu, Long et al. (2016) Noninvasive Imaging of Human Atrial Activation during Atrial Flutter and Normal Rhythm from Body Surface Potential Maps. PLoS One 11:e0163445
Zhou, Zhaoye; Jin, Qi; Chen, Lin Yee et al. (2016) Noninvasive Imaging of High-Frequency Drivers and Reconstruction of Global Dominant Frequency Maps in Patients With Paroxysmal and Persistent Atrial Fibrillation. IEEE Trans Biomed Eng 63:1333-1340
Yu, Long; Zhou, Zhaoye; He, Bin (2015) Temporal Sparse Promoting Three Dimensional Imaging of Cardiac Activation. IEEE Trans Med Imaging 34:2309-19
Han, Chengzong; Pogwizd, Steven M; Yu, Long et al. (2015) Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure. Am J Physiol Heart Circ Physiol 308:H108-14
Zhou, Zhaoye; Han, Chengzong; Yang, Ting et al. (2015) Noninvasive imaging of 3-dimensional myocardial infarction from the inverse solution of equivalent current density in pathological hearts. IEEE Trans Biomed Eng 62:468-76
Hoeker, Gregory S; Hood, Ashleigh R; Katra, Rodolphe P et al. (2014) Sex differences in ?-adrenergic responsiveness of action potentials and intracellular calcium handling in isolated rabbit hearts. PLoS One 9:e111411

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