Date of Award

5-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Chair/Advisor

Dr. Ethan Kung

Committee Member

Dr. Delphine Dean

Committee Member

Dr. Joseph Singapogu

Committee Member

Dr. Richard Figliola

Committee Member

Dr. Arman Kilic

Abstract

Cardiovascular modeling has traditionally relied on either purely computational or purely experimental approaches, each with inherent limitations. Computational models offer flexibility for exploring a wide range of hemodynamic conditions but often struggle to resolve multi-timescale phenomena such as rotordynamic interactions in a blood pump and its concomitant physiologic responses. In contrast, physical mock circulatory loops (MCLs) can reproduce localized hemodynamics with high fidelity but cannot replicate closed-loop cardiac feedback. These respective shortcomings motivated the emergence of hybrid MCLs, which integrate computational models with physical MCLs to exploit their complementary strengths. However, early hybrid implementations required real-time feedback control at the computational-experimental interface, which limited their application to conditions with robust signal-to-noise ratios and minimal actuation latency.

To address these challenges, the Physiology Simulation Coupled Experiment (PSCOPE) framework was developed as a novel paradigm in hybrid cardiovascular modeling. PSCOPE replaces real-time control with an asynchronous coupling algorithm that enables iterative exchange of boundary conditions between a lumped-parameter network (LPN) simulation and a physical MCL, thereby achieving a closed-loop hybrid physiology model that simulates hemodynamic responses under experimental conditions. Prior studies verified PSCOPE’s capacity to replicate multiscale dynamics and model left ventricular assist device (LVAD)-supported circulation. Nonetheless, initial implementations were confined to rigid MCLs and could not accommodate volumetrically dynamic experiments; i.e., MCLs with periodic volume changes.

This dissertation introduces an enhanced PSCOPE methodology that overcomes this limitation. The proposed method features an improved coupling algorithm that supports a broader range of experimental conditions within the hybrid framework, including volumetrically dynamic, multi-branch, and rigid MCLs. These experimental conditions were represented via virtual experiments, i.e., mathematical proxies of physical MCLs, to verify the accuracy of the closed-loop hemodynamics obtained using the improved PSCOPE method. In each case, the virtual experiment was embedded directly within the LPN to produce a reference “true” solution that could verify the analogous hybrid solution obtained by coupling the same virtual experiment to the LPN using the PSCOPE protocol.

Building on this foundation, the enhanced PSCOPE method was applied to patient-specific modeling of LVAD-supported circulation. First, we demonstrated the framework’s predictive capabilities by creating digital twins to forecast post-LVAD implantation hemodynamics. In this context, a digital twin refers to a PSCOPE model that couples a patient-specific LPN to an in-vitro LVAD flow loop to model LVAD-supported physiology. For post-LVAD physiology predictions, each patient-specific LPN was parameterized using pre-LVAD clinical hemodynamics, and the in-vitro LVAD was configured to reflect the clinical post-LVAD settings. Consequently, the digital twin anticipates the patient’s early postoperative hemodynamics, and its predictions are validated against clinical measurements. Finally, we developed and verified a novel empirical model of LVAD-supported left ventricular function by embedding it within PSCOPE digital twins to reproduce patient-specific preload and afterload sensitivities of HeartMate 3-supported circulation. In this application, the patient-specific LPNs were parameterized using ramp-test hemodynamics acquired across multiple HeartMate 3 speed settings.


In summary, this dissertation presents a substantial advancement of the PSCOPE framework, extending its utility to more physiologically relevant and experimentally diverse hemodynamic conditions. Through validation in LVAD-supported patients, the enhanced methodology demonstrates its potential as a clinically informative tool for guiding surgical planning and optimizing patient-specific therapeutic strategies.

Author ORCID Identifier

0000-0003-2132-0807

Available for download on Monday, May 31, 2027

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