● Cardiac anatomy and microstructure using histology and diffusion tensor MRI, and the structural underpinning of cardiac function.
● Ex vivo cardiac MRI, confocal microscopy, image analysis, preclinical models of cardiovascular disease, cardiac Langendorff preparations.
● Previously researched novel measures of diastolic function using echocardiography, and on the development of anti-thrombin nanoparticles for site-specific anticoagulation without increasing bleeding risk.
● Other interests include: analytics and optimization, having completed his Masters of Operations Research with a thesis titled "Optimal Electricity Distribution Tariff Design"
● Skills include: animal handling and surgery, MRI scanning, preclinical echocardiography, signal and image processing, programming and teaching.
● Investigated the relationship between cardiomyocyte branching and cellular location using extended volume confocal microscopy [Ref 1]
● Examined the diastolic pressure-volume relationship using both MRI and ex vivo techniques (Virtual Physiological Human Conference Abstract)
● The use of ACE inhibitors alters the myocardial collagen organization, reducing deposition between sheetlets [Ref 2]
● Published methods chapter detailing the formulation of anti-thrombin PFC nanoparticles [Ref 3]
Daniel Ennis, Postdoctoral Faculty Sponsor
Formulation and Characterization of Antithrombin Perfluorocarbon Nanoparticles.
Methods in molecular biology (Clifton, N.J.)
2020; 2118: 111–20
Thrombin, a major protein involved in the clotting cascade by the conversion of inactive fibrinogen to fibrin, plays a crucial role in the development of thrombosis. Antithrombin nanoparticles enable site-specific anticoagulation without increasing bleeding risk. Here we outline the process of making and the characterization of bivalirudin and D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone (PPACK) nanoparticles. Additionally, the characterization of these nanoparticles, including particle size, zeta potential, and quantification of PPACK/bivalirudin loading, is also described.
View details for DOI 10.1007/978-1-0716-0319-2_8
View details for PubMedID 32152974
Myocardial Laminar Organization Is Retained in Angiotensin-Converting Enzyme Inhibitor Treated SHRs
View details for DOI 10.1007/s11340-020-00622-4
Microstructurally Motivated Constitutive Modeling of Heart Failure Mechanics.
Heart failure (HF) is one of the leading causes of death worldwide. HF is associated with substantial microstructural remodeling, which is linked to changes in left ventricular geometry and impaired cardiac function. The role of myocardial remodeling in altering the mechanics of failing hearts remains unclear. Structurally based constitutive modeling provides an approach to improve understanding of the relationship between biomechanical function and tissue organization in cardiac muscle during HF. In this study, we used cardiac magnetic resonance imaging and extended-volume confocal microscopy to quantify the remodeling of left ventricular geometry and myocardial microstructure of healthy and spontaneously hypertensive rat hearts at the ages of 12 and 24months. Passive cardiac mechanical function was characterized using left ventricular pressure-volume compliance measurements. We have developed a, to our knowledge, new structurally based biomechanical constitutive equation built on parameters quantified directly from collagen distributions observed in confocal images of the myocardium. Three-dimensional left ventricular finite element models were constructed from subject-specific invivo magnetic resonance imaging data. The structurally based constitutive equation was integrated into geometrically subject-specific finite element models of the hearts and used to investigate the underlying mechanisms of ventricular dysfunction during HF. Using a single pair of material parameters for all hearts, we were able to produce compliance curves that reproduced all of the experimental compliance measurements. The value of this study is not limited to reproducing the mechanical behavior of healthy and diseased hearts, but it also provides important insights into the structure-function relationship of diseased myocardium that will help pave the way toward more effective treatments for HF.
View details for DOI 10.1016/j.bpj.2019.09.038
View details for PubMedID 31653449
Increased cardiac work provides a link between systemic hypertension and heart failure
2017; 5 (1)
The spontaneously hypertensive rat (SHR) is an established model of human hypertensive heart disease transitioning into heart failure. The study of the progression to heart failure in these animals has been limited by the lack of longitudinal data. We used MRI to quantify left ventricular mass, volume, and cardiac work in SHRs at age 3 to 21 month and compared these indices to data from Wistar-Kyoto (WKY) controls. SHR had lower ejection fraction compared with WKY at all ages, but there was no difference in cardiac output at any age. At 21 month the SHR had significantly elevated stroke work (51 ± 3 mL.mmHg SHR vs. 24 ± 2 mL.mmHg WKY; n = 8, 4; P < 0.001) and cardiac minute work (14.2 ± 1.2 L.mmHg/min SHR vs. 6.2 ± 0.8 L.mmHg/min WKY; n = 8, 4; P < 0.001) compared to control, in addition to significantly larger left ventricular mass to body mass ratio (3.61 ± 0.15 mg/g SHR vs. 2.11 ± 0.008 mg/g WKY; n = 8, 6; P < 0.001). SHRs showed impaired systolic function, but developed hypertrophy to compensate and successfully maintained cardiac output. However, this was associated with an increase in cardiac work at age 21 month, which has previously demonstrated fibrosis and cell death. The interplay between these factors may be the mechanism for progression to failure in this animal model.
View details for DOI 10.14814/phy2.13104
View details for Web of Science ID 000392243200001
View details for PubMedID 28082430
View details for PubMedCentralID PMC5256162
- Three-Dimensional Quantification of Myocardial Collagen Morphology from Confocal Images SPRINGER INTERNATIONAL PUBLISHING AG. 2017: 3–12
- Image-driven constitutive modeling of myocardial fibrosis INTERNATIONAL JOURNAL FOR COMPUTATIONAL METHODS IN ENGINEERING SCIENCE & MECHANICS 2016; 17 (3): 211–21
- Microstructural Remodelling and Mechanics of Hypertensive Heart Disease SPRINGER-VERLAG BERLIN. 2015: 382–89
- Field-Based Parameterisation of Cardiac Muscle Structure from Diffusion Tensors SPRINGER-VERLAG BERLIN. 2015: 146–54