scholarly journals Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection

2016 ◽  
Vol 7 ◽  
Author(s):  
Mona Alimohammadi ◽  
Cesar Pichardo-Almarza ◽  
Obiekezie Agu ◽  
Vanessa Díaz-Zuccarini
Keyword(s):  
Aortic Dissection ◽  
Scale Model ◽  
Patient Specific ◽  
Multi Scale

scholarly journals Computational tools for clinical support: a multi-scale compliant model for haemodynamic simulations in an aortic dissection based on multi-modal imaging data

2017 ◽  
Vol 14 (136) ◽  
pp. 20170632 ◽  
Author(s):  
Mirko Bonfanti ◽  
Stavroula Balabani ◽  
John P. Greenwood ◽  
Sapna Puppala ◽  
Shervanthi Homer-Vanniasinkam ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Moving Boundary ◽  
Computational Cost ◽  
False Lumen ◽  
Patient Specific ◽  
Model Parameters ◽  
High Morbidity ◽  
Multi Scale ◽  
Clinical Support

Aortic dissection (AD) is a vascular condition with high morbidity and mortality rates. Computational fluid dynamics (CFD) can provide insight into the progression of AD and aid clinical decisions; however, oversimplified modelling assumptions and high computational cost compromise the accuracy of the information and impede clinical translation. To overcome these limitations, a patient-specific CFD multi-scale approach coupled to Windkessel boundary conditions and accounting for wall compliance was developed and used to study a patient with AD. A new moving boundary algorithm was implemented to capture wall displacement and a rich in vivo clinical dataset was used to tune model parameters and for validation. Comparisons between in silico and in vivo data showed that this approach successfully captures flow and pressure waves for the patient-specific AD and is able to predict the pressure in the false lumen (FL), a critical variable for the clinical management of the condition. Results showed regions of low and oscillatory wall shear stress which, together with higher diastolic pressures predicted in the FL, may indicate risk of expansion. This study, at the interface of engineering and medicine, demonstrates a relatively simple and computationally efficient approach to account for arterial deformation and wave propagation phenomena in a three-dimensional model of AD, representing a step forward in the use of CFD as a potential tool for AD management and clinical support.

scholarly journals Multi-scale computational models of the airways to unravel the pathophysiological mechanisms in asthma and chronic obstructive pulmonary disease (AirPROM)

2013 ◽  
Vol 3 (2) ◽  
pp. 20120057 ◽  
Author(s):  
K. S. Burrowes ◽  
J. De Backer ◽  
R. Smallwood ◽  
P. J. Sterk ◽  
I. Gut ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Heart Function ◽  
Scale Model ◽  
Patient Specific ◽  
Chronic Obstructive ◽  
Disease Heterogeneity ◽  
Obstructive Pulmonary Disease ◽  
Pathophysiological Mechanisms ◽  
Multi Scale

The respiratory system comprises several scales of biological complexity: the genes, cells and tissues that work in concert to generate resultant function. Malfunctions of the structure or function of components at any spatial scale can result in diseases, to the detriment of gas exchange, right heart function and patient quality of life. Vast amounts of data emerge from studies across each of the biological scales; however, the question remains: how can we integrate and interpret these data in a meaningful way? Respiratory disease presents a huge health and economic burden, with the diseases asthma and chronic obstructive pulmonary disease (COPD) affecting over 500 million people worldwide. Current therapies are inadequate owing to our incomplete understanding of the disease pathophysiology and our lack of recognition of the enormous disease heterogeneity: we need to characterize this heterogeneity on a patient-specific basis to advance healthcare. In an effort to achieve this goal, the AirPROM consortium ( Air way disease Pr edicting O utcomes through patient-specific computational M odelling) brings together a multi-disciplinary team and a wealth of clinical data. Together we are developing an integrated multi-scale model of the airways in order to unravel the complex pathophysiological mechanisms occurring in the diseases asthma and COPD.

Multi-scale pulsatile CFD modeling of thrombus transport in a patient-specific LVAD implantation

2017 ◽  
Vol 27 (5) ◽  
pp. 1022-1039 ◽  
Author(s):  
Ray O. Prather ◽  
Alain Kassab ◽  
Marcus William Ni ◽  
Eduardo Divo ◽  
Ricardo Argueta-Morales ◽  
...  
Keyword(s):  
Field Measurements ◽  
Lumped Parameter Model ◽  
Scale Model ◽  
Cfd Modeling ◽  
Patient Specific ◽  
Physiological Data ◽  
Peripheral Vasculature ◽  
Ventricular Assist ◽  
Content Type ◽  
Multi Scale

Purpose Predictive models implemented in medical procedures can potentially bring great benefit to patients and represent a step forward in targeted treatments based on a patient’s physiological condition. It is the purpose of this paper to outline such a model. Design/methodology/approach A multi-scale 0D-3D model based on patient specific geometry combines a 0-dimensional lumped parameter model (LPM) with a 3D computational fluid dynamics (CFD) analysis coupled in time, to obtain physiologically viable flow parameters. Findings A comparison of physiological data gathered from literature with flow-field measurements in this model shows the viability of this method in relation to potential predictions of pathological flows repercussions and candidate treatments. Research limitations/implications A limitation of the model is the absence of compliance in the walls in the CFD fluid domain; however, compliance of the peripheral vasculature is accounted for by the LPM. Currently, an attempt is in progress to extend this multi-scale model to account for the fluid-structure interaction of the ventricular assist device vasculature and hemodynamics. Originality/value This work reports on a predictive pulsatile flow model that can be used to investigate surgical alternatives to reduce strokes in LVADs.

scholarly journals A Combined In Vivo, In Vitro, In Silico Approach for Patient-Specific Haemodynamic Studies of Aortic Dissection

2020 ◽  
Vol 48 (12) ◽  
pp. 2950-2964
Author(s):  
Mirko Bonfanti ◽  
Gaia Franzetti ◽  
Shervanthi Homer-Vanniasinkam ◽  
Vanessa Díaz-Zuccarini ◽  
Stavroula Balabani
Keyword(s):  
Aortic Dissection ◽  
In Silico ◽  
Clinical Decision ◽  
Patient Specific ◽  
Type B ◽  
Non Invasive ◽  
Cfd Models ◽  
Numerical Predictions

AbstractThe optimal treatment of Type-B aortic dissection (AD) is still a subject of debate, with up to 50% of the cases developing late-term complications requiring invasive intervention. A better understanding of the patient-specific haemodynamic features of AD can provide useful insights on disease progression and support clinical management. In this work, a novel in vitro and in silico framework to perform personalised studies of AD, informed by non-invasive clinical data, is presented. A Type-B AD was investigated in silico using computational fluid dynamics (CFD) and in vitro by means of a state-of-the-art mock circulatory loop and particle image velocimetry (PIV). Both models not only reproduced the anatomical features of the patient, but also imposed physiologically-accurate and personalised boundary conditions. Experimental flow rate and pressure waveforms, as well as detailed velocity fields acquired via PIV, are extensively compared against numerical predictions at different locations in the aorta, showing excellent agreement. This work demonstrates how experimental and numerical tools can be developed in synergy to accurately reproduce patient-specific AD blood flow. The combined platform presented herein constitutes a powerful tool for advanced haemodynamic studies for a range of vascular conditions, allowing not only the validation of CFD models, but also clinical decision support, surgical planning as well as medical device innovation.

scholarly journals Virtual surgeries in patients with congenital heart disease: a multi-scale modelling test case

2011 ◽  
Vol 369 (1954) ◽  
pp. 4316-4330 ◽  
Author(s):  
A. Baretta ◽  
C. Corsini ◽  
W. Yang ◽  
I. E. Vignon-Clementel ◽  
A. L. Marsden ◽  
...  
Keyword(s):  
Boundary Conditions ◽  
Congenital Heart ◽  
Closed Loop ◽  
Three Dimensional ◽  
Scale Model ◽  
Patient Specific ◽  
Loop Model ◽  
Multi Scale ◽  
Venae Cavae ◽  
Lumped Parameter

The objective of this work is to perform a virtual planning of surgical repairs in patients with congenital heart diseases—to test the predictive capability of a closed-loop multi-scale model. As a first step, we reproduced the pre-operative state of a specific patient with a univentricular circulation and a bidirectional cavopulmonary anastomosis (BCPA), starting from the patient's clinical data. Namely, by adopting a closed-loop multi-scale approach, the boundary conditions at the inlet and outlet sections of the three-dimensional model were automatically calculated by a lumped parameter network. Successively, we simulated three alternative surgical designs of the total cavopulmonary connection (TCPC). In particular, a T-junction of the venae cavae to the pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O-TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop model consisting of a lumped parameter network representing the whole circulation and a patient-specific three-dimensional finite volume model of the BCPA with detailed pulmonary anatomy was built. The three TCPC alternatives were investigated in terms of energetics and haemodynamics. Effects of exercise were also investigated. Results showed that the pre-operative caval flows should not be used as boundary conditions in post-operative simulations owing to changes in the flow waveforms post-operatively. The multi-scale approach is a possible solution to overcome this incongruence. Power losses of the Y-TCPC were lower than all other TCPC models both at rest and under exercise conditions and it distributed the inferior vena cava flow evenly to both lungs. Further work is needed to correlate results from these simulations with clinical outcomes.

scholarly journals A multi-scale pipeline linking drug transcriptomics with pharmacokinetics predicts in vivo interactions of tuberculosis drugs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph M. Cicchese ◽  
Awanti Sambarey ◽  
Denise Kirschner ◽  
Jennifer J. Linderman ◽  
Sriram Chandrasekaran
Keyword(s):  
Drug Interactions ◽  
Scale Model ◽  
Relative Distribution ◽  
Combination Therapies ◽  
Multi Scale ◽  
Machine Learning Model ◽  
Drug Regimens ◽  
New Treatments

AbstractTuberculosis (TB) is the deadliest infectious disease worldwide. The design of new treatments for TB is hindered by the large number of candidate drugs, drug combinations, dosing choices, and complex pharmaco-kinetics/dynamics (PK/PD). Here we study the interplay of these factors in designing combination therapies by linking a machine-learning model, INDIGO-MTB, which predicts in vitro drug interactions using drug transcriptomics, with a multi-scale model of drug PK/PD and pathogen-immune interactions called GranSim. We calculate an in vivo drug interaction score (iDIS) from dynamics of drug diffusion, spatial distribution, and activity within lesions against various pathogen sub-populations. The iDIS of drug regimens evaluated against non-replicating bacteria significantly correlates with efficacy metrics from clinical trials. Our approach identifies mechanisms that can amplify synergistic or mitigate antagonistic drug interactions in vivo by modulating the relative distribution of drugs. Our mechanistic framework enables efficient evaluation of in vivo drug interactions and optimization of combination therapies.

Patient-Specific Modeling and Hemodynamic Simulation in Healthy and Diseased Coronary Arteries

2012 ◽  
Author(s):  
Lucian Itu ◽  
Puneet Sharma ◽  
Xudong Zheng ◽  
Viorel Mihalef ◽  
Ali Kamen ◽  
...  
Keyword(s):  
Patient Specific ◽  
Multi Scale ◽  
Routine Clinical Setting ◽  
Patient Specific Modeling ◽  
Artery Disease ◽  
Diagnostic Modalities ◽  
Causes Of Deaths ◽  
Computational Resources

Coronary Artery Disease is one of the leading causes of deaths worldwide, with an estimated 7.2 million deaths each year. In spite of the improvements in imaging and other diagnostic modalities, the incidence of premature morbidity and mortality is still very high, the main reason being the lack of accurate in-vivo and in-vitro patient-specific estimates for diagnosis and disease progression. Recently, CFD-based models have been proposed for analyzing the coronary circulation [1, 2]. The main challenges for such methods are the lack of patient-specific data (anatomy, boundary conditions), inefficient multi-scale coupling and computational resources. These challenges limit the scope of such methods in a routine clinical setting.

scholarly journals Electro-Mechanical Whole-Heart Digital Twins: A Fully Coupled Multi-Physics Approach

Mathematics ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1247
Author(s):  
Tobias Gerach ◽  
Steffen Schuler ◽  
Jonathan Fröhlich ◽  
Laura Lindner ◽  
Ekaterina Kovacheva ◽  
...  
Keyword(s):  
Human Heart ◽  
Clinical Decision Making ◽  
Scale Model ◽  
Patient Specific ◽  
Loop Model ◽  
Multi Scale ◽  
Atrial Ablation ◽  
Digital Twins ◽  
Whole Heart ◽  
Fully Coupled

Mathematical models of the human heart are evolving to become a cornerstone of precision medicine and support clinical decision making by providing a powerful tool to understand the mechanisms underlying pathophysiological conditions. In this study, we present a detailed mathematical description of a fully coupled multi-scale model of the human heart, including electrophysiology, mechanics, and a closed-loop model of circulation. State-of-the-art models based on human physiology are used to describe membrane kinetics, excitation-contraction coupling and active tension generation in the atria and the ventricles. Furthermore, we highlight ways to adapt this framework to patient specific measurements to build digital twins. The validity of the model is demonstrated through simulations on a personalized whole heart geometry based on magnetic resonance imaging data of a healthy volunteer. Additionally, the fully coupled model was employed to evaluate the effects of a typical atrial ablation scar on the cardiovascular system. With this work, we provide an adaptable multi-scale model that allows a comprehensive personalization from ion channels to the organ level enabling digital twin modeling.

scholarly journals A multi-scale model of the yeast chromosome-segregation system

2018 ◽  
Author(s):  
Cai Tong Ng ◽  
Li Deng ◽  
Chen Chen ◽  
Hong Hwa Lim ◽  
Jian Shi ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Scale Model ◽  
Microtubule Depolymerization ◽  
Multi Scale ◽  
Yeast Chromosome ◽  
Dividing Cells ◽  
Electron Cryotomography ◽  
Binding Position

ABSTRACTIn dividing cells, depolymerizing spindle microtubules move chromosomes by pulling at their kinetochores. While kinetochore subcomplexes have been studied extensively in vitro, little is known about their in vivo structure and interactions with microtubules or their response to spindle damage. Here we combine electron cryotomography of serial cryosections with genetic and pharmacological perturbation to study the yeast chromosome-segregation machinery at molecular resolution in vivo. Each kinetochore microtubule has one (rarely, two) Dam1C/DASH outer-kinetochore assemblies.Dam1C/DASH only contacts the flat surface of the microtubule and does so with its flexible “bridges”. In metaphase, 40% of the Dam1C/DASH assemblies are complete rings; the rest are partial rings. Ring completeness and binding position along the microtubule are sensitive to kinetochore attachment and tension, respectively. Our study supports a model in which each kinetochore must undergo cycles of conformational change to couple microtubule depolymerization to chromosome movement.

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