scholarly journals A Simulation Protocol for Exercise Physiology in Fontan Patients Using a Closed Loop Lumped-Parameter Model

2014 ◽  
Vol 136 (8) ◽  
Author(s):  
Ethan Kung ◽  
Giancarlo Pennati ◽  
Francesco Migliavacca ◽  
Tain-Yen Hsia ◽  
Richard Figliola ◽  
...  
Keyword(s):  
Clinical Data ◽  
Closed Loop ◽  
Exercise Physiology ◽  
Clinical Findings ◽  
Lumped Parameter Model ◽  
Patient Specific ◽  
Specific Reference ◽  
Fontan Patient ◽  
Lumped Parameter ◽  
Fontan Patients

Background: Reduced exercise capacity is nearly universal among Fontan patients, though its etiology is not yet fully understood. While previous computational studies have attempted to model Fontan exercise, they did not fully account for global physiologic mechanisms nor directly compare results against clinical and physiologic data. Methods: In this study, we developed a protocol to simulate Fontan lower-body exercise using a closed-loop lumped-parameter model describing the entire circulation. We analyzed clinical exercise data from a cohort of Fontan patients, incorporated previous clinical findings from literature, quantified a comprehensive list of physiological changes during exercise, translated them into a computational model of the Fontan circulation, and designed a general protocol to model Fontan exercise behavior. Using inputs of patient weight, height, and if available, patient-specific reference heart rate (HR) and oxygen consumption, this protocol enables the derivation of a full set of parameters necessary to model a typical Fontan patient of a given body-size over a range of physiologic exercise levels. Results: In light of previous literature data and clinical knowledge, the model successfully produced realistic trends in physiological parameters with exercise level. Applying this method retrospectively to a set of clinical Fontan exercise data, direct comparison between simulation results and clinical data demonstrated that the model successfully reproduced the average exercise response of a cohort of typical Fontan patients. Conclusion: This work is intended to offer a foundation for future advances in modeling Fontan exercise, highlight the needs in clinical data collection, and provide clinicians with quantitative reference exercise physiologies for Fontan patients.

scholarly journals Systems biology informed neural networks (SBINN) predict response and novel combinations for PD-1 checkpoint blockade

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michelle Przedborski ◽  
Munisha Smalley ◽  
Saravanan Thiyagarajan ◽  
Aaron Goldman ◽  
Mohammad Kohandel
Keyword(s):  
Neural Networks ◽  
Systems Biology ◽  
Clinical Data ◽  
Treatment Protocol ◽  
Response Prediction ◽  
Clinical Findings ◽  
Patient Specific ◽  
Patient Response ◽  
Triple Combination Therapy ◽  
Parameter Values

AbstractAnti-PD-1 immunotherapy has recently shown tremendous success for the treatment of several aggressive cancers. However, variability and unpredictability in treatment outcome have been observed, and are thought to be driven by patient-specific biology and interactions of the patient’s immune system with the tumor. Here we develop an integrative systems biology and machine learning approach, built around clinical data, to predict patient response to anti-PD-1 immunotherapy and to improve the response rate. Using this approach, we determine biomarkers of patient response and identify potential mechanisms of drug resistance. We develop systems biology informed neural networks (SBINN) to calculate patient-specific kinetic parameter values and to predict clinical outcome. We show how transfer learning can be leveraged with simulated clinical data to significantly improve the response prediction accuracy of the SBINN. Further, we identify novel drug combinations and optimize the treatment protocol for triple combination therapy consisting of IL-6 inhibition, recombinant IL-12, and anti-PD-1 immunotherapy in order to maximize patient response. We also find unexpected differences in protein expression levels between response phenotypes which complement recent clinical findings. Our approach has the potential to aid in the development of targeted experiments for patient drug screening as well as identify novel therapeutic targets.

DIRECT CORONARY COUPLING APPROACH FOR COMPUTING FFRCT

2016 ◽  
Vol 17 (03) ◽  
pp. 1750043
Author(s):  
XINZHOU XIE ◽  
MINWEN ZHENG ◽  
XU DUAN ◽  
SONGYUN XIE ◽  
YUANYUAN WANG
Keyword(s):  
Clinical Setting ◽  
Coupling Efficiency ◽  
Lumped Parameter Model ◽  
Patient Specific ◽  
Fractional Flow ◽  
Invasive Approach ◽  
Flow Reserve ◽  
Lumped Parameter ◽  
Routine Clinical Setting ◽  
Coupling Approach

With the advances in computational fluid dynamics (CFD) and image-based modeling techniques, fractional flow reserve (FFR) can be computed from coronary computed tomography angiography (CTA) scans (FFRCT). However, this non-invasive approach requires large-scale computational resources, which limits its application in routine clinical setting. A 3D–0D coupling approach is proposed to improve the coupling efficiency of FFRCT. Aortic–root is modeled by a lumped parameter model and connected with the models of left ventricle and systemic circulation. With this approach, the interested coronary regions can be directly coupled to the lumped parameter model, resulting in a significant reduction (up to 20 times reduction) in the volume of the CFD computing domain. The proposed approach is applied to a patient-specific model and compared with previous non-reduced approach. Results show that the computed coronary flow rates, pressure waveforms and FFRCT contours by the proposed approach are consistent well with that of the non-reduced approach. These results demonstrate that the proposed approach can reduce the CFD computing domain of FFRCT significantly while maintaining the similar accuracy as compared with the non-reduced approach, and it can be further employed to promote FFRCT in routine clinical setting.

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 Calibration of an Electrical Analog Model of Liver Hemodynamics in Fontan Patients

2020 ◽  
Vol 143 (3) ◽  
Author(s):  
Elyar Abbasi Bavil ◽  
Matthew G. Doyle ◽  
Charlotte Debbaut ◽  
Rachel M. Wald ◽  
Luc Mertens ◽  
...  
Keyword(s):  
Pressure Gradient ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Lumped Parameter Model ◽  
Patient Specific ◽  
Model Parameters ◽  
Liver Health ◽  
Liver Hemodynamics ◽  
Fontan Patients

Abstract Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient (PPG)). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model (LPM) of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of PPGs in these patients. An existing LPM of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step toward models suitable to assess liver health in Fontan patients and improve its long-term management.

Investigation of Pulsatile Hemodynamics in Patient-Specific Fontan Templates With Fenestration

2011 ◽  
Author(s):  
Onur Dur ◽  
Greggory Housler ◽  
Ergin Kocyildirim ◽  
Haifa Hong ◽  
Jinfen Liu ◽  
...  
Keyword(s):  
Superior Vena ◽  
Pulmonary Arteries ◽  
Vena Cava ◽  
Surgical Techniques ◽  
Surgical Reconstruction ◽  
Patient Specific ◽  
Fontan Patient ◽  
Third Stage ◽  
Patients Experience ◽  
Fontan Patients

The third stage for palliative surgical reconstruction for children with functional single-ventricle (SV) physiology is the completion of the total cavopulmonary connection (TCPC), where the superior vena cava (SVC) and inferior vena cava (IVC) are routed directly into the pulmonary arteries. Approximately 5000 newborns in the US each year join to the existing SV (or Fontan) patient population, along with increasing numbers of adult Fontan patients surviving longer due to the advances in surgical techniques and post-op management. Although most post-operative Fontan patients experience an acceptable quality of life, their lifespan is shorter than normal with a significant number of these patients developing late hemodynamic complications (failing Fontan) and requiring heart transplantation. Donor shortage and the high-risk nature of transplantation for these complex and often very ill patients demand alternative therapeutic options [1].

An Automated Simulation Protocol for Exercise Physiology in Fontan Patients Using a Closed-Loop Lumped-Parameter Model

2013 ◽  
Author(s):  
Ethan Kung ◽  
Alessandro Giardini ◽  
Francesco Migliavacca ◽  
Giancarlo Pennati ◽  
Tain-Yen Hsia ◽  
...  
Keyword(s):  
Exercise Physiology ◽  
Fontan Procedure ◽  
Pulmonary Arteries ◽  
Standard Of Care ◽  
Lumped Parameter Model ◽  
Lumped Parameter ◽  
Simulation Protocol ◽  
Automated Simulation ◽  
Clinical Measurements ◽  
The Right

Single ventricle physiology is one of the most severe forms of congenital heart disease in which an infant is born with only one functional pumping chamber. These patients must go through a series of surgical procedures concluding with the Fontan procedure, which connects the superior and inferior vena cavae to the pulmonary arteries, bypassing the right side of the heart entirely. Reduced exercise capacity is a common morbidity in Fontan patients1, leading to decreased quality of life, and the etiology of lowered exercise performance remains unclear. Exercise conditions place high demands on the cardiovascular system; any good surgical design must consider the behavior of the system at stress. Invasive clinical measurements during exercise pose many challenges and are typically not standard of care. There is a need to better understand Fontan exercise physiology and to predict clinical outcomes using computational tools.

scholarly journals STUDY OF UNCERTAINTIES ON A 0D MODEL OF THE SYSTEMIC CIRCULATION

2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Gilmar Ferreira Da Silva Filho ◽  
Rafael Alves Bonfim De Queiroz ◽  
Luis Paulo Da Silva Barra ◽  
Bernardo Martins Rocha
Keyword(s):  
Sensitivity Analysis ◽  
Computational Models ◽  
Clinical Decision Making ◽  
Systemic Circulation ◽  
Lumped Parameter Model ◽  
Patient Specific ◽  
Accurate Estimation ◽  
Clinical Patient ◽  
Lumped Parameter ◽  
Input Parameters

Cardiovascular system is intensely researched to understand the intricate nature of the heart and blood circulation. Nowadays we have well evolved computational models which are useful in many ways for the understanding and analysis of physiological and pathophysiological conditions of the heart. However, the practical use of these models and their results for clinical decision making in specific patients is not straightforward. In this context, models predictions must be accurate and reliable, which can be assessed by quantification of uncertainties in the predictions and sensitivity analysis of the input parameters. Lumped parameter models for the cardiovascular physiology can provide useful data for clinical patient-specific applications. However, the accurate estimation of all parameters of these models is a difficult task, and therefore the determination of the most sensitive parameters is an important step towards the calibration of these models. We perform uncertainty quantification and sensitivity analysis based on generalised polynomial chaos expansion in a lumped parameter model for the systemic circulation. The objective of this work is to verify the effect of uncertainties from input parameters on the predictions of the models and to identify parameters that contribute significantly to relevant quantities of interest. Numerical experiments are performed and results indicate a set of the most relevant parameters in the context of these models.

scholarly journals A patient-specific lumped-parameter model of coronary circulation

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Zheng Duanmu ◽  
Min Yin ◽  
Xueling Fan ◽  
Xilan Yang ◽  
Xiaoyu Luo
Keyword(s):  
Coronary Circulation ◽  
Lumped Parameter Model ◽  
Patient Specific ◽  
Lumped Parameter
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