Advances in the brain-inspired computing space are growing at a rapid rate, and many of these emerging strategies are in the field of neuromorphic control, robotics, and sensor development, just to ...name a few. These innovations are disruptive in their own right and have numerous, multi-dimensional medical applications within precision medicine, telematics, device development, and informed clinical decision making. For this discussion, I will define brain-inspired computing in the scope of simulating the architecture of the brain and discuss the realization of integrating hardware and other technologies with the applications of medicine, along with the considerations for the regulatory pathway for approval and evaluating the risk/consequences of failure modes. This perspective is a call for continued discussion of the development of a pathway for translating these technologies into medical treatment and diagnostic strategies. The aim is to align with global regulatory bodies and ensure that regulation does not limit the capacity of these emerging innovations while ensuring patient safety and clinical efficacy. It is my perspective that it is and will continue to be critical that these technologies are correctly perceived and understood in the lens of multiple disciplines in order to reach their full potential for medical applications.
The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and ...anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O'Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies.
The latest technologies associated with implantable physiological monitoring devices can record multiple channels of data (including: heart rates and rhythms, activity, temperature, impedance and ...posture), and coupled with powerful software applications, have provided novel insights into the physiology of animals in the wild. This perspective details past challenges and lessons learned from the uses and developments of implanted biologgers designed for human clinical application in our research on free-ranging American black bears (
Ursus americanus
). In addition, we reference other research by colleagues and collaborators who have leveraged these devices in their work, including: brown bears (
Ursus arctos
), grey wolves (
Canis lupus
), moose (
Alces alces
), maned wolves (
Chrysocyon brachyurus
) and southern elephant seals (
Mirounga leonina
). We also discuss the potentials for applications of such devices across a range of other species. To date, the devices described have been used in fifteen different wild species, with publications pending in many instances. We have focused our physiological research on the analyses of heart rates and rhythms and thus special attention will be paid to this topic. We then discuss some major expected step changes such as improvements in sensing algorithms, data storage, and the incorporation of next-generation short-range wireless telemetry. The latter provides new avenues for data transfer, and when combined with cloud-based computing, it not only provides means for big data storage but also the ability to readily leverage high-performance computing platforms using artificial intelligence and machine learning algorithms. These advances will dramatically increase both data quantity and quality and will facilitate the development of automated recognition of extreme physiological events or key behaviours of interest in a broad array of environments, thus further aiding wildlife monitoring and management.
This article is part of the theme issue ‘Measuring physiology in free-living animals (Part I)’.
The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high ...performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of
human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm
in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging
, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10
m with a porosity of 20 kg/m
on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.
We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates ...donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits.
Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform. Three groups (n = 4 each) were differentiated by perfusate: (1) isolated red blood cells (RBCs) (current clinical standard for OCS); (2) whole blood (WB); and (3) acellular buffered dextran-albumin solution (analogous to STEEN solution).
Only the RBC and WB groups met clinical standards for transplantation at 8 hours; our primary analysis at 24H focused on perfusion with WB versus RBC. The WB perfusate was superior (vs RBC) for maintaining stability of all monitored parameters, including the following mean 24H measures: pulmonary artery pressure (6.8 vs 9.0 mm Hg), reservoir volume replacement (85 vs 1607 mL), and PaO2:FiO2 ratio (541 vs 223). Acellular perfusion was limited to 6 hours on the OCS system due to prohibitively high vascular resistance, edema, and worsening compliance.
The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and buffered dextran-albumin solution for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.
Remarkably, American black bears (Ursus americanus) are capable of varying their heart rates to coincide with their breathing, creating pauses of 30 s or more, yet they do not appear to suffer from ...embolic events. We evaluated some features of the clotting cascade of black bears, providing novel insights into the underlying mechanisms they evoke for embolic protection during hibernation. We measured activated clotting time, prothrombin time and activated partial thromboplastin time during early denning (December), late denning (March) and summer (August). Activated clotting time during early hibernation was ∼3 times longer than that observed among non-hibernating animals. Clotting time was reduced later in hibernation, when bears were within ∼1 month of emerging from dens. Prothrombin time was similar for each seasonal time point, whereas activated partial thromboplastin time was highest during early denning and decreased during late denning and summer. We also examined D-dimer concentration to assess whether the bears were likely to have experienced embolic events. None of the non-parturient bears exceeded a D-dimer concentration of 250 ng ml
(considered the clinical threshold for embolism in mammals). Our findings suggest there is unique expression of the clotting cascade in American black bears during hibernation, in which extrinsic pathways are maintained but intrinsic pathways are suppressed. This was evaluated by a significant difference between the activated clotting time and activated partial thromboplastin time during the denning and non-denning periods. These changes are likely adaptive, to avoid clotting events during states of immobilization and/or periods of asystole. However, an intact extrinsic pathway allows for healing of external injuries and/or foreign body responses.
Three-dimensional printing is an additive manufacturing method that builds objects from digitally generated computational models. Core technologies behind three-dimensional printing are evolving ...rapidly with major advances in materials, resolution, and speed that enable greater realism and higher accuracy. These improvements have led to novel applications of these processes in the medical field.
The process of going from a medical image data set (computed tomography, magnetic resonance imaging, ultrasound) to a physical three-dimensional print includes several steps that are described. Medical images originate from Digital Imaging and Communications in Medicine files or data sets, the current standard for storing and transmitting medical images. Via Digital Imaging and Communications in Medicine manipulation software packages, a segmentation process, and manual intervention by an expert user, three-dimensional digital and printed models can be constructed in great detail.
Cardiovascular medicine is one of the fastest growing applications for medical three-dimensional printing. The technology is more frequently being used for patient and clinician education, preprocedural planning, and medical device design and prototyping. We report on three case studies, describing how our three-dimensional printing has contributed to the care of cardiac patients at the University of Minnesota.
Medical applications of computational three-dimensional modeling and printing are already extensive and growing rapidly and are routinely used for visualizing complex anatomies from patient imaging files to plan surgeries and create surgical simulators. Studies are needed to determine whether three-dimensional printed models are cost effective and can consistently improve clinical outcomes before they become part of routine clinical practice.
Stent implantation in bifurcated coronary lesions is technically challenging so that procedural refinements are continuously investigated. Novel procedure modeling and intracoronary imaging ...techniques may offer critical insights on stent deformations and stent-wall interactions during bifurcation stenting procedures. Thus, we assessed coronary bifurcation stenting techniques using multimodal imaging and 3D modeling in reanimated swine hearts. Harvested swine hearts were reanimated using Visible Heart® methodologies and (under standard fluoroscopic guidance) used to test 1-stent (provisional and inverted provisional) and 2-stent (culotte, TAP and DK-crush) techniques on bifurcations within various coronary vessels using commercially available devices. Intracoronary angioscopy and frequency-domain optical-coherence-tomography (OCT) were obtained during the procedures. 3D OCT reconstruction and micro-computed tomography 3D modeling (post heart fixations) were used to assess stent deformations and stent-wall interactions. We conducted multiple stenting procedures and collected unique endoscopic and OCT images (and subsequent computational models from micro-CT) to assess stent deformations and device/wall interactions during different steps of bifurcation stenting procedures. Endoscopy, micro-CT and virtual reality processing documented that different 1- and 2-stent techniques, practiced according to experts’ recommended steps, achieve optimal post-intervention stent conformation. As compared with intra-procedural endoscopy, software-generated 3D OCT images accurately depicted stent deformations during 1-stent techniques. On the opposite, during more complex 2-stent techniques, some defects were appreciated at 3D OCT reconstruction despite optimal 2D OCT images. This study provided unique insights regarding both stent deformations occurring in the course of bifurcation stenting and the efficacy of OCT to visualize them.
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