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1. Computational Cardiovascular Flow Analysis with the Variational Multiscale Methods

   https://doi.org/10.25073/jaec.201932.245  

   Takizawa, Kenji; Bazilevs, Yuri; E. Tezduyar, Tayfun; Hsu, Ming-Chen (June 2019, Journal of Advanced Engineering and Computation)

   Computational cardiovascular flow analysis can provide valuable information to medical doctors in a wide range of patientspecific cases, including cerebral aneurysms, aortas and heart valves. The computational challenges faced in this class of flow analyses also have a wide range. They include unsteady flows, complex cardiovascular geometries, moving boundaries and interfaces, such as the motion of the heart valve leaflets, contact between moving solid surfaces, such as the contact between the leaflets, and the fluid–structure interaction between the blood and the cardiovascular structure. Many of these challenges have been or are being addressed by the Space–Time Variational Multiscale (ST-VMS) method, Arbitrary Lagrangian–Eulerian VMS (ALE-VMS) method, and the VMS-based Immersogeometric Analysis (IMGA-VMS), which serve as the core computational methods, and the special methods used in combination with them. We provide an overview of the core and special methods and present examples of challenging computations carried out with these methods, including aorta and heart valve flow analyses. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited. 

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2. Recent advances in blood rheology: a review

   https://doi.org/10.1039/d1sm01212f  

   Beris, Antony N.; Horner, Jeffrey S.; Jariwala, Soham; Armstrong, Matthew J.; Wagner, Norman J. (December 2021, Soft Matter)

   Due to the potential impact on the diagnosis and treatment of various cardiovascular diseases, work on the rheology of blood has significantly expanded in the last decade, both experimentally and theoretically. Experimentally, blood has been confirmed to demonstrate a variety of non-Newtonian rheological characteristics, including pseudoplasticity, viscoelasticity, and thixotropy. New rheological experiments and the development of more controlled experimental protocols on more extensive, broadly physiologically characterized, human blood samples demonstrate the sensitivity of aspects of hemorheology to several physiological factors. For example, at high shear rates the red blood cells elastically deform, imparting viscoelasticity, while at low shear rates, they form “rouleaux” structures that impart additional, thixotropic behavior. In addition to the advances in experimental methods and validated data sets, significant advances have also been made in both microscopic simulations and macroscopic, continuum, modeling, as well as novel, multiscale approaches. We outline and evaluate the most promising of these recent developments. Although we primarily focus on human blood rheology, we also discuss recent observations on variations observed across some animal species that provide some indication on evolutionary effects. 

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3. Lateral thinking in syndromic congenital cardiovascular disease

   https://doi.org/10.1242/dmm.049735  

   Kocere, Agnese; Lalonde, Robert L.; Mosimann, Christian; Burger, Alexa (May 2023, Disease Models & Mechanisms)

   ABSTRACT Syndromic birth defects are rare diseases that can present with seemingly pleiotropic comorbidities. Prime examples are rare congenital heart and cardiovascular anomalies that can be accompanied by forelimb defects, kidney disorders and more. Whether such multi-organ defects share a developmental link remains a key question with relevance to the diagnosis, therapeutic intervention and long-term care of affected patients. The heart, endothelial and blood lineages develop together from the lateral plate mesoderm (LPM), which also harbors the progenitor cells for limb connective tissue, kidneys, mesothelia and smooth muscle. This developmental plasticity of the LPM, which founds on multi-lineage progenitor cells and shared transcription factor expression across different descendant lineages, has the potential to explain the seemingly disparate syndromic defects in rare congenital diseases. Combining patient genome-sequencing data with model organism studies has already provided a wealth of insights into complex LPM-associated birth defects, such as heart-hand syndromes. Here, we summarize developmental and known disease-causing mechanisms in early LPM patterning, address how defects in these processes drive multi-organ comorbidities, and outline how several cardiovascular and hematopoietic birth defects with complex comorbidities may be LPM-associated diseases. We also discuss strategies to integrate patient sequencing, data-aggregating resources and model organism studies to mechanistically decode congenital defects, including potentially LPM-associated orphan diseases. Eventually, linking complex congenital phenotypes to a common LPM origin provides a framework to discover developmental mechanisms and to anticipate comorbidities in congenital diseases affecting the cardiovascular system and beyond. 

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4. A dimension-reduced variational approach for solving physics-based inverse problems using generative adversarial network priors and normalizing flows

   https://doi.org/10.1016/j.cma.2023.116682  

   Dasgupta, Agnimitra; Patel, Dhruv V; Ray, Deep; Johnson, Erik A; Oberai, Assad A (February 2024, Computer Methods in Applied Mechanics and Engineering)

   We propose a novel modular inference approach combining two different generative models — generative adversarial networks (GAN) and normalizing flows — to approximate the posterior distribution of physics-based Bayesian inverse problems framed in high-dimensional ambient spaces. We dub the proposed framework GAN-Flow. The proposed method leverages the intrinsic dimension reduction and superior sample generation capabilities of GANs to define a low-dimensional data-driven prior distribution. Once a trained GAN-prior is available, the inverse problem is solved entirely in the latent space of the GAN using variational Bayesian inference with normalizing flow-based variational distribution, which approximates low-dimensional posterior distribution by transforming realizations from the low-dimensional latent prior (Gaussian) to corresponding realizations of a low-dimensional variational posterior distribution. The trained GAN generator then maps realizations from this approximate posterior distribution in the latent space back to the high-dimensional ambient space. We also propose a two-stage training strategy for GAN-Flow wherein we train the two generative models sequentially. Thereafter, GAN-Flow can estimate the statistics of posterior-predictive quantities of interest at virtually no additional computational cost. The synergy between the two types of generative models allows us to overcome many challenges associated with the application of Bayesian inference to large-scale inverse problems, chief among which are describing an informative prior and sampling from the high-dimensional posterior. GAN-Flow does not involve Markov chain Monte Carlo simulation, making it particularly suitable for solving large-scale inverse problems. We demonstrate the efficacy and flexibility of GAN-Flow on various physics-based inverse problems of varying ambient dimensionality and prior knowledge using different types of GANs and normalizing flows. Notably, one of the applications we consider involves a 65,536-dimensional inverse problem of phase retrieval wherein an object is reconstructed from sparse noisy measurements of the magnitude of its Fourier transform. 

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5. Simulation of unsteady blood flows in a patient-specific compliant pulmonary artery with a highly parallel monolithically coupled fluid-structure interaction algorithm

   Kong, F; kheyfets, V; Finol, E; Cai, X.-C. (April 2019, International journal for numerical methods in biomedical engineering)

   Computational fluid dynamics (CFD) is increasingly used to study blood flows in patient-specific arteries for understanding certain cardiovascular diseases. The techniques work quite well for relatively simple problems but need improvements when the problems become harder when (a) the geometry becomes complex (eg, a few branches to a full pulmonary artery), (b) the model becomes more complex (eg, fluid-only to coupled fluid-structure interaction), (c) both the fluid and wall models become highly nonlinear, and (d) the computer on which we run the simulation is a supercomputer with tens of thousands of processor cores. To push the limit of CFD in all four fronts, in this paper, we develop and study a highly parallel algorithm for solving a monolithically coupled fluid-structure system for the modeling of the interaction of the blood flow and the arterial wall. As a case study, we consider a patient-specific, full size pulmonary artery obtained from computed tomography (CT) images, with an artificially added layer of wall with a fixed thickness. The fluid is modeled with a system of incompressible Navier-Stokes equations, and the wall is modeled by a geometrically nonlinear elasticity equation. As far as we know, this is the first time the unsteady blood flow in a full pulmonary artery is simulated without assuming a rigid wall. The proposed numerical algorithm and software scale well beyond 10 000 processor cores on a supercomputer for solving the fluid-structure interaction problem discretized with a stabilized finite element method in space and an implicit scheme in time involving hundreds of millions of unknowns. 

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