Electroporation is considered a novel means for treating tissue using high-voltage, short-duration direct current (DC) pulses to elicit different cellular responses. Varying the parameters of the therapeutic pulses allows for either temporary or permanent cellular damage. It is believed that applied DC pulses disrupt cell membranes, with larger electric fields causing more damage. A wide variety of input parameters allows for the ability to fine tune this technology to target different tissue types. Since the delivery of energy is based on an electric field compared to a thermal field, there is also potential to better target specific areas while minimizing collateral tissue damage. The ability to apply electroporation therapy, in its latest technological form, is currently being explored to understand its possible clinical applications.
This chapter offers an overview of optical mapping concepts and provides details related to various applications of this technique to visualize the normal and abnormal rhythms of the heart. It enables the visualization of activation propagation and determination of relative conduction velocity of electrical activity of the heart and can be used to assess action potential duration at various levels of repolarization. Optical mapping can also be utilized to visualize different types of arrhythmias in the heart, such as ventricular tachycardia and ventricular fibrillation. This technique has been widely employed to visualize, predict, and control the onset of abnormal cardiac rhythms such as alternans. Optical mapping can also be beneficial in studying acute changes in cardiac electrophysiological properties of the heart during various disease states and also to develop and evaluate therapeutic strategies.
Cardiothoracic transplantation research dates back to the late 1800s, yet the first human heart transplantation did not occur until 1967. Today, more and more centers worldwide are performing such procedures with increasing success, long-term survival rates, and, importantly, with an improved quality of life for recipients. Much work remains to increase the number of available hearts and lungs for these transplants, but progress is being made for many reasons that are discussed in this chapter. The use of ex vivo lung and heart perfusion technologies along with pharmacological advancements (e.g., preservation solutions) has expanded the time available between organ recovery and transplantation, allowing for enhanced functional assessment and providing a platform for therapeutic delivery. In this chapter, we provide a brief history of cardiothoracic transplantation, review the current state of transplantation procedures, and discuss future directions for research and technological advancements.
Pre- and postimplant evaluations of implantable cardiac devices require innovative and critical testing during all phases of the design process. The Visible Heart Project was successfully launched in 1997, and 3 years later, the Atlas of Human Cardiac Anatomy website was published online. The Visible Heart methodologies and Atlas website provide users with a unique experimental toolset and a comprehensive anatomical archive to improve understanding of human cardiac anatomy and preclinical device testing results. To date, Visible Heart methodologies have been used to reanimate over 80 human hearts, all considered nonviable for transplantation. These studies provide imaging datasets that are then uploaded to the Atlas, a free-access website featuring novel images of functional and fixed human cardiac anatomies from >500 human heart specimens. Furthermore, this website includes educational tutorials on anatomy, physiology, congenital heart disease, and various imaging modalities. Examples of clinically approved devices that were present at the time of in vitro reanimation, or were subsequently delivered into perfusion-fixed specimens (i.e., pacing and defibrillator leads, catheters, valves, annuloplasty rings, leadless pacemakers, and stents), can be found online within the Device Tutorial. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography and magnetic resonance images of various heart specimens. Importantly, the methodologies developed and employed within the Visible Heart laboratory have led to a more comprehensive understanding of human cardiac anatomy, physiology, and device–tissue interactions, building the foundation of knowledge needed for modern cardiovascular device design and development.
In the last 24 years, functional magnetic resonance imaging (fMRI) has catapulted into the most widely used methodology for mapping human brain function noninvasively. Its ability to monitor physiological processes associated with brain function, while maintaining high degrees of spatial and temporal precision, has proven to be instrumental for basic neuroscience. Routine clinical scanning has advanced from 1.5 and 3.0 T to magnets capable of operating routinely at 7 T. In addition to increased field strength, significant efforts have been devoted to developing pulse sequences aimed at further challenging the fMRI spatial–temporal acquisition limits. Ultimately, further development of high-field high-resolution imaging techniques for human applications will eventually open doors to noninvasive neuroscience investigations which were never thought previously to be possible. This chapter discusses several strategies, possibilities, and considerations with fMRI, which make the selection of the most optimal approach unclear.
Brain energy metabolism relies predominantly on glucose and oxygen metabolism to generate adenosine triphosphate (ATP), a high-energy phosphate compound. ATP is essential for maintaining basal electrophysiological activity in the resting brain, as well as supporting increased neuronal activity evoked by stimulation and/or task performance. Investigating the complex bioenergetic processes in the human brain has required the development of sophisticated neuroimaging techniques capable of noninvasively and quantitatively measuring the cerebral metabolic rates of glucose and oxygen consumption and ATP turnover, as well as the nicotinamide adenine dinucleotide redox state. It has been demonstrated that in vivo multinuclear magnetic resonance spectroscopy (MRS) and imaging techniques have such ability, especially when performed at ultrahigh magnetic fields (7 T and higher). This chapter provides a brief review of recent advancements in in vivo MRS techniques, in the quest of understanding neuroenergetics and function in preclinical animal and human brains.
The potential for developing gene therapy technologies is evident from the recent surge in research activity. The use of these emerging technologies, along with blastocyst complementation, could greatly enhance our ability to produce exogenic organs and cells in a relatively short period of time. Furthermore, the generation of human–animal organ chimeras, together with their associated vasculature, could be developed to overcome the global problem of organ shortage for transplantation, as well as complications associated with immune rejection. It will be imperative that we understand the underlying conditions for stem cell growth in a developmental environment, to determine if cross-species chimeras can be therapeutically developed. Importantly, the combination of gene editing and blastocyst complementation has created an entirely new and exciting field of medicine, one that we envision will have a critical role for precision medicine.
Transcranial magnetic stimulation (TMS) is a technique for noninvasive brain stimulation to modulate function, with a range of applications across neuroscience research and the clinical management of brain disorders. Currently, there are two major categories of applied TMS paradigms: (1) the application of single pulses with high temporal precision for brain mapping and various diagnostic objectives and (2) neural stimulation with trains of repeated pulses to alter cortical excitability, primarily for therapeutic purposes. Recently, exploration of noninvasive neuromodulation has increased considerably in both scientific and clinical research fields. The unique capabilities to both assess and change brain circuits noninvasively have made TMS a widely adopted and fast-growing applied methodology in neuromodulation. This chapter reviews recent advances, challenges, and future trends in the field of TMS as applied to the human motor systems.
This chapter reviews the anatomical and functional aspects of human cardiac heart valves, in relation to surgical and percutaneous therapies. Understanding the underlying features and structures of the heart valves is essential when designing and/or implementing repair/replacement devices for valvular disease treatment. Pertinent history and current technologies in the field of valve repair and replacement procedures are reviewed, as they provide insights into the future of valve bioprosthesis engineering. In addition, Visible Heart methodologies will be highlighted for their unique role in valvular anatomical/functional studies and preclinical testing of repair/replacement technologies.
Being a medical device innovator is highly rewarding because you can impact human health, while being fully intellectually engaged and stimulated. Successful innovators need training and knowledge in a range of associated topics including the general innovation process, identification and definition of clinical needs, device prototyping and testing, preclinical and clinical research, regulatory and reimbursement issues, intellectual property, and business development fundamentals. One must be a lifelong student of medical device innovation, particularly because these and other topics evolve over time. For example, 3D printing, digital simulation, and immersive visualization are changing how devices are prototyped. In addition, combination device and drug therapies are changing how medical technologies are regulated, and the field of health informatics is using the explosion of medical data to drive clinical and reimbursement decisions. This chapter discusses some educational opportunities for new and experienced medical device innovators including courses, training programs, conferences, workshops, and books.
Transcranial direct current stimulation (tDCS) employs low levels of electrical energy, applied across the scalp. In this chapter, we review the physics and proposed underlying mechanisms of tDCS, along with more recent work investigating the reported effects of tDCS on human behavior and brain activity. We further review the state of tDCS research for motor and cognitive rehabilitation and highlight several ongoing efforts by Institute for Engineering in Medicine researchers developing novel tDCS-based interventions. Finally, we present a vision for the future of tDCS research, with an emphasis on the key challenges ahead, namely, functional and anatomical target specification and bringing tDCS into mainstream clinical domains.
We have a shared responsibility to provide medical solutions, therapies, and devices to improve the lives of underserved patients worldwide. Novel design and manufacturing technologies as well as new sales and distribution tools create opportunities for the medical device ecosystem to innovate therapies and products. Further, lessons learned from high-volume manufacturing and the agility needed for low-volume manufacturing can be leveraged to deliver highly efficient health care for patients worldwide. Public–private partnerships in this field present a proven model for creating a platform for collaboration, innovative approaches, and solutions. These collaborations will drive constructive discussions, pilot projects, and a broadened awareness of the opportunities for emerging health-care solutions.
Developing a new medical device requires more than a good idea and good engineering. This chapter presents a structured method and best practices to guide innovators through the steps of medical device development. Practical suggestions are offered for screening an innovative medical device based on its technical, market, and financial feasibility, how to cost effectively test new medical devices for safety and efficacy, and how to protect intellectual property and navigate the patent process. The complexities of regulation, reimbursement, and financing of medical devices are discussed as well. Following best practices for new medical device development does not guarantee success, but it does minimize the risk of developing the product.
Electrical recording and stimulation circuits have contributed to various novel neuroscience studies and clinical applications for treating disease. Many neurological disorders have their own gradual degradation of neuronal circuitry; thus, it becomes necessary to accurately study the connections amongst neurons. Therefore, there is a demand today for generating and enhancing neuroscience tools which could allow individuals to study circuit dynamics, by recording and stimulating neurons with high spatiotemporal resolution. Existing neural technologies suffer from degraded signal quality, large size, low channel count, and they also consume enormous power. Further, associated large stimulation artifacts cause saturation, which limits the current recorders from monitoring neuron activities in a window up to a few hundred milliseconds after a stimulation onsite. This chapter describes innovative neuroengineering platform technologies and miniaturized devices that enable more precise neural stimulation, recording, and subsequent processing function. The proposed technologies feature high-precision, low-power, and low-noise elements, all in a very compact system. They also provide the ability to simultaneously record and stimulate neurons, to enable novel experimental designs that ultimately improve our understanding of the human brain's circuits and functions.
