The lectures are designed to be primers for the labs. You will learn about advanced tools and technologies for cardiovascular therapeutics, diagnostics and medical device design.
Friday, November 10
Finding Order in the Electrical Chaos of Atrial Fibrillation
Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice and a major cause of embolic stroke. Yet, despite more than 100 years of research and speculation, the mechanism of AF is not well understood and therapy is often ineffective. The use of voltage-sensitive probes and high- resolution video imaging in isolated animal hearts has provided support for the hypothesis that AF may be driven by one, or a small number of high-frequency electrical sources called “rotors”. In this presentation, I will address the following questions: (1) What is mechanisms underlying AF maintenance? (2) What is a rotor and how is it formed? (3) What technologies are available in the basic lab to map the atria and find rotors during AF? (4) What electrical and structural conditions are needed for a rotor to maintain AF indefinitely? And (5) what maneuvers can be used to find rotors when they are hiding from view?
Can Wearables Transform How We Manage Cardiovascular Disease?
Current and future uses of wearables will be discussed including: 1) How are wearables being currently used by patients with cardiovascular disease and how the health care system incorporates wearables into current day practices of cardiovascular disease. 2) The potential of wearables for the improvement of patient-centered care with increase quality and value; what does the future hold; 3) Do academic medical centers play a role digital healthcare?
Animal Models of Deep Vein Thrombosis
Deep vein thrombosis and its sequelae are associated with high morbidity and mortality representing a significant health care concern. Unfortunately, even with newer therapies, the incidence of this disease has not significantly changed over the past 25 years. In this presentation, I will review several experimental animal models that are being used to study the mechanisms of venous thrombus generation, amplification, and resolution. Preclinical and translational animal models can help accelerate the development of new pharmacologic and medical interventions targeted at limiting vascular inflammation and thrombosis. The advantages and limitations of different animal models will also be discussed. Related methodologies of animal anesthesia, phlebotomy, pathology, and in vitro hemostasis testing are also reviewed.
Small Animal Magnetic Resonance Imaging & Exercise Therapeutics
Preclinical imaging can be used to further research in basic science, therapeutic development, and translation to the clinic. We will briefly cover magnetic resonance imaging (MRI) physics and place preclinical MRI in context with other modalities. Next, we will focus on methods to visualize and quantify structure and function of the cardiovascular system, in health and disease. Limitations and variability of animal models will be discussed. How one might incorporate complementary tools, such as computational fluid dynamics, will be described. The clinical relevance and, hence, the importance of preclinical implementation of the use of exercise as a prophylactic and therapeutic strategy will be presented. Overall, emphasis will be placed on how highly-optimized preclinical MRI or, when necessary, the novel implementation of sequences predominantly reserved for the clinic results in unique conclusions that might only be gleaned by using such technology.
Saturday, November 11
Histotripsy: Image-guided Ultrasound Therapy for Non-Invasive Cardiovascular Surgery
Wouldn’t it be great to perform a surgery without incision or bleeding? “Histotripsy” is a new non-invasive ultrasound ablation technique that fractionates and removes tissue. Histotrispy was invented at the University of Michigan, with Dr. Xu as a co-inventor. Using high pressure, microsecond-length ultrasound pulses applied from outside the body and focused to the diseased tissue, Histotripsy produces a cluster of energetic microbubbles at the target tissue. These microbubbles, each similar in size to individual cells, function as “mini-scalpels” to fractionate cell and tissue structures. The intervening tissue between the target tissue and the skin is not damaged. No incision or injection of external agents is required. The treatment is guided by real-time imaging (ultrasound or MR). Histotripsy has potential for many clinical applications where non-invasive tissue removal is desired. This lecture will cover the development of Histotripsy for treatment of blood clots and plaque, congenital heart disease, and hemorrhagic stroke.
The impact of computing on health care has grown exponentially in the last few years. The paradigm of patient-specific modeling has enabled revolutionary applications such as disease research and medical device design and performance evaluation. Computational modeling is also increasingly present in noninvasive diagnostics, in which data and modeling are combined to save the patient from undergoing expensive, dangerous, and potentially unnecessary diagnostic procedures, and even in virtual surgical planning, in which an optimal intervention is identified by simulating different alternative designs prior to the surgical procedure. These advances have not just been limited to the realm of research and academia. The FDA has been recently advocating the development of in silico trials, in which computer modeling and simulations are used to develop and assess devices and drugs, including their potential risk to the public, before being tested in live clinical trials. In this lecture, we will provide an overview of the patient-specific modeling paradigm and its key applications.
Designing Microenvironments to Direct Stem Cells for Cardiovascular Tissue Regeneration
Regenerative medicine aims to create replacement tissues and organs by utilizing the highly regenerative potentials of stem cells or induced stem cells. There is a growing recognition of 3D matrix microenvironments in regulating the fate and function of stem cells. A key challenge facing regenerative medicine is to create the microenvironments that can recapitulate those in a developmental or healing program to maintain stemness, to accelerate proliferation, or to guide stem cell differentiation along a specific therapeutic lineage. Our team takes a biomimetic approach to design biodegradable polymers to modulate 3D microenvironments on the micro, nano and molecular scales for stem cells to regenerate cardiovascular tissues. This lecture will focus on biomaterials, scaffolds, cell microcarriers and biomolecule delivery systems for cardiovascular tissue regeneration. Several examples will be presented to demonstrate the impact of biomimetic materials and stem cells in cardiovascular therapies.
Targeted Drug Delivery
Nanotechnology is prominent in medicine for various applications that span use in understanding cellular and molecular interactions to development of technologies for disease characterization, detection and treatment. In drug delivery, numerous studies have evaluated systemically injectable nanoparticles for the targeted delivery of multiple therapeutic and contrast agents. Despite the high promise of nanotechnology, only a few of these technologies have made it to clinical utility. It is likely that the limited translation of nanotechnology based interventions to date is due to the lack of mechanistic understanding of cellular and molecular interactions of these technologies owing to the complexity of biological systems in health and diseases. This talk will offer perspective on the current limitations to translation of drug delivery systems to clinical utility and how we can better exploit these understandings to generate highly effective nanotechnologies for the early detection, imaging and treatment of human diseases.
Moving Novel Medical Therapies From Academics To Industry: One Person’s Journey
There is an ever-increasing need for novel, cost-effective diagnostic and therapeutic approaches in the treatment of cardiovascular and other diseases. Many of these ideas originate in the academic or private practice setting. However, the path from inception of an idea to become a widely clinically used, commercially successful therapy is complex and expensive.
The main goal of this presentation is to provide an overview and some practical insights of how device-based therapies are identified, funded and developed from the “back of the napkin” through commercialization.
Sunday, November 12
Focusing on Areas of Technological Improvements for Long Term Mechanical Circulatory Support Devices
Implantable mechanical circulatory support devices represent an alternative long term treatment option for patients with advanced heart failure who are failing conventional medical therapies. The use of MCS devices has significantly increased in the US due to lack of alternative treatment options for these patients, particularly the lack of access to heart transplantation, whose availability is limited by donor organ shortages. Significant technology innovation has improved clinical outcomes with MCS devices, however, important adverse events remain and some technology improvements have been associated with unintended consequences in altering the physiology of human biology. The lecture will review important areas of need for technology improvement and how current MCS devices are evaluated both in the bench and clinical setting.
New Techniques in Vascular Trauma Management
This presentation will be based upon research that has, in part, been performed within the Jobst Vascular Research Laboratory. It is closely related to my research interest in defining therapies for the treatment of non-compressible torso hemorrhage (NCTH) and shock states using Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). Emergency arterial access is a critical first step in this process and advances in this area will also be highlighted. A summary of the data thus far for REBOA will be presented, as well as some potential areas of advanced innovation related to these technologies. While data from translational large animal models will be discussed, clinical research and outcomes for humans will also be highlighted.