Artificial Intelligence, Computational Simulations, and Extended Reality in Cardiovascular Interventions.

Artificial intelligence, computational simulations, and extended reality, among other 21st century computational technologies, are changing the health care system. To collectively highlight the most recent advances and benefits of artificial intelligence, computational simulations, and extended reality in cardiovascular therapies, we coined the abbreviation AISER. The review particularly focuses on the following applications of AISER: 1) preprocedural planning and clinical decision making; 2) virtual clinical trials, and cardiovascular device research, development, and regulatory approval; and 3) education and training of interventional health care professionals and medical technology innovators. We also discuss the obstacles and constraints associated with the application of AISER technologies, as well as the proposed solutions. Interventional health care professionals, computer scientists, biomedical engineers, experts in bioinformatics and visualization, the device industry, ethics committees, and regulatory agencies are expected to streamline the use of AISER technologies in cardiovascular interventions and medicine in general.

Three dimensional reconstruction of coronary artery stents from optical coherence tomography: experimental validation and clinical feasibility.

The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps: 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and final stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro-computed tomography (µCT) and stereoscopy as references. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. The experimental and clinical studies showed that our algorithm (1) can reproduce the complex spatial stent configuration with high precision and reproducibility, (2) is feasible in 3D reconstructing stents deployed in bifurcations, and (3) enables CFD studies to assess the local hemodynamic environment within the stent. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can lay the ground for optimization of stenting procedures, patient-specific computational stenting simulations, and research and development of new stent scaffolds and stenting techniques.

Computational and experimental mechanical performance of a new everolimus-eluting stent purpose-built for left main interventions.

Left main (LM) coronary artery bifurcation stenting is a challenging topic due to the distinct anatomy and wall structure of LM. In this work, we investigated computationally and experimentally the mechanical performance of a novel everolimus-eluting stent (SYNERGY MEGATRON) purpose-built for interventions to large proximal coronary segments, including LM. MEGATRON stent has been purposefully designed to sustain its structural integrity at higher expansion diameters and to provide optimal lumen coverage. Four patient-specific LM geometries were 3D reconstructed and stented computationally with finite element analysis in a well-validated computational stent simulation platform under different homogeneous and heterogeneous plaque conditions. Four different everolimus-eluting stent designs (9-peak prototype MEGATRON, 10-peak prototype MEGATRON, 12-peak MEGATRON, and SYNERGY) were deployed computationally in all bifurcation geometries at three different diameters (i.e., 3.5, 4.5, and 5.0 mm). The stent designs were also expanded experimentally from 3.5 to 5.0 mm (blind analysis). Stent morphometric and biomechanical indices were calculated in the computational and experimental studies. In the computational studies the 12-peak MEGATRON exhibited significantly greater expansion, better scaffolding, smaller vessel prolapse, and greater radial strength (expressed as normalized hoop force) than the 9-peak MEGATRON, 10-peak MEGATRON, or SYNERGY (p < 0.05). Larger stent expansion diameters had significantly better radial strength and worse scaffolding than smaller stent diameters (p < 0.001). Computational stenting showed comparable scaffolding and radial strength with experimental stenting. 12-peak MEGATRON exhibited better mechanical performance than the 9-peak MEGATRON, 10-peak MEGATRON, or SYNERGY. Patient-specific computational LM stenting simulations can accurately reproduce experimental stent testing, providing an attractive framework for cost- and time-effective stent research and development.

Effects of periurethral neuromuscular electrical stimulation on the voiding frequency in rats.

INTRODUCTION AND HYPOTHESIS: This study aims to test the hypothesis that a urethra-to-bladder inhibitory pathway exists through which periurethral neuromuscular electrical stimulation (NMES) inhibits overactive bladder contractions in rats. METHODS: Bladder overactivity was induced in 22 female Sprague Dawley rats by injection of ketamine/xylazine/acepromizine (K/X/A). A bipolar electrode was placed surgically in the periurethral region to deliver NMES. Intravesical pressure, bladder inter-contraction interval (ICI) and voided volume (VV) were monitored while the bladder was continuously infused with saline. RESULTS: K/X/A induced more frequent bladder contractions (ICI = 48.6 +/- 20.1 s, before cutting the pubo-symphasis) compared to a 10-min ICI induced by urethane. NMES significantly increased ICI (63.1 +/- 31.3 s before vs. 97.2 +/- 42.9 s after NMES, p < 0.001) and VV (0.063 = 0.041 ml before vs. 0.088 = 0.044 ml after NMES, p < 0.02). CONCLUSIONS: Injection of K/X/A may potentially be used as a model of bladder overactivity. NMES inhibits bladder contractions in rats with bladder overactivity, which supports the existence of a urethra-to-bladder inhibitory pathway.

Model Convolution: A Computational Approach to Digital Image Interpretation.

Digital fluorescence microscopy is commonly used to track individual proteins and their dynamics in living cells. However, extracting molecule-specific information from fluorescence images is often limited by the noise and blur intrinsic to the cell and the imaging system. Here we discuss a method called "model-convolution," which uses experimentally measured noise and blur to simulate the process of imaging fluorescent proteins whose spatial distribution cannot be resolved. We then compare model-convolution to the more standard approach of experimental deconvolution. In some circumstances, standard experimental deconvolution approaches fail to yield the correct underlying fluorophore distribution. In these situations, model-convolution removes the uncertainty associated with deconvolution and therefore allows direct statistical comparison of experimental and theoretical data. Thus, if there are structural constraints on molecular organization, the model-convolution method better utilizes information gathered via fluorescence microscopy, and naturally integrates experiment and theory.

Anterograde microtubule transport drives microtubule bending in LLC-PK1 epithelial cells.

Microtubules (MTs) have been proposed to act mechanically as compressive struts that resist both actomyosin contractile forces and their own polymerization forces to mechanically stabilize cell shape. To identify the origin of MT bending, we directly observed MT bending and F-actin transport dynamics in the periphery of LLC-PK1 epithelial cells. We found that F-actin is nearly stationary in these cells even as MTs are deformed, demonstrating that MT bending is not driven by actomyosin contractility. Furthermore, the inhibition of myosin II activity through the use of blebbistatin results in microtubules that are still dynamically bending. In addition, as determined by fluorescent speckle microscopy, MT polymerization rarely results, if ever, in bending. We suppressed dynamic instability using nocodazole, and we observed no qualitative change in the MT bending dynamics. Bending most often results from anterograde transport of proximal portions of the MT toward a nearly stationary distal tip. Interestingly, we found that in an in vitro kinesin-MT gliding assay, MTs buckle in a similar manner. To make quantitative comparisons, we measured curvature distributions of observed MTs and found that the in vivo and in vitro curvature distributions agree quantitatively. In addition, the measured MT curvature distribution is not Gaussian, as expected for a thermally driven semiflexible polymer, indicating that thermal forces play a minor role in MT bending. We conclude that many of the known mechanisms of MT deformation, such as polymerization and acto-myosin contractility, play an inconsequential role in mediating MT bending in LLC-PK1 cells and that MT-based molecular motors likely generate most of the strain energy stored in the MT lattice. The results argue against models in which MTs play a major mechanical role in LLC-PK1 cells and instead favor a model in which mechanical forces control the spatial distribution of the MT array.

Analysis of microtubule curvature.

The microtubule cytoskeleton in living cells generate and resist mechanical forces to mediate fundamental cell processes, including cell division and migration. Recent advances in digital fluorescence microscopy have enabled the direct observation of bending of individual microtubules in living cells, which has enabled quantitative estimation of the mechanical state of the microtubule array. Although a variety of mechanisms have been proposed, the precise origins of microtubule deformation in living cells remain largely obscure. To investigate these mechanisms and their relative importance in cellular processes, a method is needed to accurately quantify microtubule bending within living cells. Here we describe a method for quantification of bending, using digital fluorescence microscope images to estimate the distribution of curvature in the microtubule. Digital images of individual microtubules can be used to obtain a set of discrete x-y coordinates along the microtubule contour, which is then used to estimate the curvature distribution. Due to system noise and digitization error, the estimate will be inaccurate to some degree. To quantify the inaccuracy, a computational model is used to simulate both the bending of thermally driven microtubules and their observation by digital fluorescence microscopy. This allows for direct comparison between experimental and simulated images, a method which we call model convolution microscopy. We assess the accuracy of various methods and present a suitable method for estimating the curvature distribution for thermally driven semiflexible polymers. Finally, we discuss extensions of the method to quantify microtubule curvature in living cells.