This $686,458 Project Grant was awarded by the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research federal grant program (CFDA 93.837). The grant supports a collaborative research effort between multiple institutions, led by Yale University, to develop a quantitative, predictive model of vascular remodeling in health and disease. The key products and services to be delivered through this grant include: Characterizing the roles of vascular endothelial...
This Project Grant award from the National Heart Lung and Blood Institute (CFDA 93.837 Cardiovascular Diseases Research) provides $1,406,736 to the Palo Alto Veterans Institute for Research (PAVIR) to conduct research aimed at understanding the mechanisms and impact of coronary artery patterning. The overarching goal is to identify pathways that could stimulate coronary artery growth and collateralization, with the potential to develop new therapies to improve outcomes for individuals with...
The National Science Foundation (NSF) awarded a 3-year, $567,284 Project Grant under the Engineering program (CFDA 47.041) to Purdue University to develop a scalable Bayesian methodology for reconstructing cardiovascular hemodynamic flow fields and cardiac structure from advanced medical imaging modalities like phase-contrast MRI, 4D flow MRI, and color Doppler echocardiography. The research aims to overcome limitations in current imaging techniques, such as inaccurate velocity flow...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) aims to leverage sex-specific anatomical and functional differences to enhance treatment and improve survival outcomes for women with severe aortic stenosis (AS). The $223,750 award to Brigham & Women's Hospital Inc., a subsidiary of Partners Healthcare System Incorporated, will fund a 2-year research project focused on developing advanced...
This $516,556 Project Grant award from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) under the "Discovery and Applied Research for Technological Innovations to Improve Human Health" (CFDA 93.286) program aims to develop and validate a novel, personalized flow modeling paradigm for assessing hemodynamics of the fetal aorta. The project, conducted by Worcester Polytechnic Institute (WPI), will focus on coarctation of the aorta, a common congenital heart...
This Project Grant award from the National Science Foundation (NSF) Division of Chemical, Bioengineering, Environmental, and Transport Systems (CFDA 47.041 - Engineering) supports a $320,155 research project at Purdue University to investigate the complex flow and transport processes within microvascular networks and their impact on vascular remodeling. The key objectives are to develop a novel computational model integrated with high-resolution imaging data to gain fundamental understanding...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $293,653 to 3DT Holdings, LLC to develop a software tool for optimizing cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and left ventricular endocardial pacing (LVEP) therapies. The goal is to reduce non-responder rates and improve patient identification for these treatments, especially for patients with...
The National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research (CFDA 93.837) program, awarded a $726,205 Project Grant to the University of Pittsburgh to develop a new super-resolution intravascular ultrasound (SR-IVUS) technology. The goal is to enable effective imaging of the coronary vasa vasorum (VV) network and thin fibrous cap to assess vulnerable atherosclerotic plaque, which is a leading cause of acute coronary syndromes. The project aims to develop a...
This federal Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $656,751 to Third Coast Dynamics, Inc. to develop an artificial intelligence-based platform called "TCDFLOW" that can derive 4D hemodynamic data from routine clinical anatomic images. This will address limitations of current 4D flow MRI techniques, which require specialized equipment and expertise, by enabling the...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research Federal Grant Program (CFDA 93.837) supports research on using coronary artery calcium scoring computed tomography (CTCS) scans to develop a predictive model for heart failure risk. The $742,395 award to Case Western Reserve University aims to leverage large CTCS datasets to identify key image-based biomarkers (radiomics) across 5 pathophysiologic domains linked to heart...
MECHANISMS OF CORONARY FLOW HETEROGENEITY: IMPLICATIONS FOR CORONARY SINUS OCCLUSION THERAPY - ABSTRACT SIGNIFICANT SPATIAL HETEROGENEITY OF CORONARY BLOOD FLOW EXISTS IN THE NORMAL HEART AND IT IS EXAGGERATED IN CORONARY HEART DISEASE (CHD). DESPITE THE SIGNIFICANT CLINICAL RELEVANCE OF ISCHEMIA IN CHD, THE PHYSICAL AND BIOLOGICAL DETERMINANTS OF SPATIAL HETEROGENEITY OF CORONARY BLOOD FLOW IN HEALTH AND DISEASE REMAIN UNCERTAIN. AS A RESULT, THE MECHANISMS OF SOME TREATMENTS, SUCH AS CORONARY SINUS (CS) OCCLUSION, PULSATILE INTERMITTENT CORONARY SINUS (CS) OCCLUSION (PICSO) AND SELECTIVE AUTO-RETROPERFUSION (SARP), ARE ALSO NOT WELL UNDERSTOOD. ADVANCES IN HIGH-PERFORMANCE COMPUTING NOW MAKE IT POSSIBLE TO ATTEMPT ANATOMICALLY REALISTIC DISTRIBUTIVE MATHEMATICAL MODELS, WHERE MORPHOLOGICAL DETAILS OF THE CORONARY VASCULAR SYSTEM ARE CONSIDERED TO TRULY ELUCIDATE THE SPATIAL HETEROGENEITY OF FLOW. HENCE, OUR GENERAL OBJECTIVE IN THIS PROPOSAL IS TO DEVELOP A VALIDATED FULL MODEL OF AN AUTOREGULATED CORONARY CIRCULATION BASED ON ANATOMICALLY ACCURATE 3D DATA IN A DYNAMIC MODEL OF THE BEATING HEART; ONE THAT INTEGRATES MYOCARDIUM-VESSEL INTERACTION (MVI) AND VASOREACTIVITY, CAN EXPLAIN THE SPATIAL HETEROGENEITY OF CORONARY BLOOD FLOW IN ISCHEMIA, AND ELUCIDATE THE RATIONALE FOR THESE CS INTERVENTIONS. THE VALIDATED MODEL WILL ILLUMINATE CLINICALLY SIGNIFICANT MECHANISMS UNDERLYING THE REDISTRIBUTION OF CORONARY FLOW IN ISCHEMIA AND THE MECHANISMS OF CS INTERVENTIONS. OUR CENTRAL HYPOTHESIS IS THAT REGIONAL DIFFERENCES IN MYOCARDIAL OXYGEN (O2) DEMAND PRODUCE SPATIAL HETEROGENEITY IN CORONARY FLOW AND THAT ISCHEMIA INCREASES FLOW HETEROGENEITY BY COMPROMISING MVI AND AUTOREGULATION. DUE TO INHERENT DIFFICULTIES ASSOCIATED WITH SUBENDOCARDIAL MEASUREMENTS IN VIVO, THE ABSENCE OF A VALIDATED BIOPHYSICAL MODEL OF THE CORONARY CIRCULATION HAS BEEN A CRITICAL BARRIER TO PROGRESS. OUR PROPOSAL ADDRESSES THIS BARRIER AND HAS THE POTENTIAL TO ADVANCE SCIENTIFIC KNOWLEDGE IN MULTI-SCALE, MULTI-PHYSICS MODELING AND, ULTIMATELY, CLINICAL PRACTICE IN DIAGNOSIS AND TREATMENT OF CHD. ACCORDINGLY, THE THREE SPECIFIC AIMS ARE TO: 1) DEVELOP AN EXPERIMENTALLY VALIDATED, PHYSICS- BASED COMPUTATIONAL FRAMEWORK COUPLING AUTOREGULATED CORONARY CIRCULATION WITH CARDIAC MECHANICS. 2) ELUCIDATE THE MECHANICAL MECHANISMS OF SUBENDOCARDIAL VULNERABILITY TO ISCHEMIA. 3) DETERMINE THE MECHANICAL MECHANISM OF ACTION OF CSO, PICSO AND SARP AS WELL AS FACTORS AFFECTING THESE TREATMENTS. THIS PROPOSAL TAKES AN INTEGRATED APPROACH (THEORY, COMPUTATIONAL MODELS, AND EXPERIMENTS) TO ELUCIDATE THE RELATIONSHIP BETWEEN SPATIAL HETEROGENEITY OF PERFUSION AND CARDIAC MECHANICAL WORK, AUTOREGULATION, AND O2 CONSUMPTION UNDER PATHOLOGICAL AND TREATMENT CONDITIONS. THE PROPOSED WORK WILL PRODUCE A NOVEL COMPUTATIONAL FRAMEWORK THAT WILL BE USED TO ELUCIDATE THE KEY FACTORS CONTROLLING SUBENDOCARDIAL VULNERABILITY IN ISCHEMIA AND THE MECHANISM OF ACTIONS OF CSO, PICSO AND SARP. THE BIOPHYSICAL MODELING FRAMEWORK WILL ALSO SERVE AS A FOUNDATION FOR CONSTRUCTING PATIENT-SPECIFIC HEART MODEL BASED ON STANDARD MEDICAL IMAGING TO ASSIST IN DIAGNOSIS AND TREATMENT OF CHD