An algorithm for coupling multibranch in vitro experiment to numerical physiology simulation for a hybrid cardiovascular model

The hybrid cardiovascular modeling approach integrates an in vitro experiment with a computational lumped‐parameter simulation, enabling direct physical testing of medical devices in the context of closed‐loop physiology. The interface between the in vitro and computational domains is essential for properly capturing the dynamic interactions of the two. To this end, we developed an iterative algorithm capable of coupling an in vitro experiment containing multiple branches to a lumped‐parameter physiology simulation. This algorithm identifies the unique flow waveform solution for each branch of the experiment using an iterative Broyden\u27s approach. For the purpose of algorithm testing, we first used mathematical surrogates to represent the in vitro experiments and demonstrated five scenarios where the in vitro surrogates are coupled to the computational physiology of a Fontan patient. This testing approach allows validation of the coupling result accuracy as the mathematical surrogates can be directly integrated into the computational simulation to obtain the “true solution” of the coupled system. Our algorithm successfully identified the solution flow waveforms in all test scenarios with results matching the true solutions with high accuracy. In all test cases, the number of iterations to achieve the desired convergence criteria was less than 130. To emulate realistic in vitro experiments in which noise contaminates the measurements, we perturbed the surrogate models by adding random noise. The convergence tolerance achievable with the coupling algorithm remained below the magnitudes of the added noise in all cases. Finally, we used this algorithm to couple a physical experiment to the computational physiology model to demonstrate its real‐world applicability

A Hybrid Experimental‐Computational Modeling Framework For Cardiovascular Device Testing

Significant advances in biomedical science often leverage powerful computational and experimental modeling platforms. We present a framework named physiology simulation coupled experiment (“PSCOPE”) that can capitalize on the strengths of both types of platforms in a single hybrid model. PSCOPE uses an iterative method to couple an in vitro mock circuit to a lumped-parameter numerical simulation of physiology, obtaining closed-loop feedback between the two. We first compared the results of Fontan graft obstruction scenarios modeled using both PSCOPE and an established multiscale computational fluid dynamics method; the normalized root-mean-square error values of important physiologic parameters were between 0.1% and 2.1%, confirming the fidelity of the PSCOPE framework. Next, we demonstrate an example application of PSCOPE to model a scenario beyond the current capabilities of multiscale computational methods—the implantation of a Jarvik 2000 blood pump for cavopulmonary support in the single-ventricle circulation; we found that the commercial Jarvik 2000 controller can be modified to produce a suitable rotor speed for augmenting cardiac output by approximately 20% while maintaining blood pressures within safe ranges. The unified modeling framework enables a testing environment which simultaneously operates a medical device and performs computational simulations of the resulting physiology, providing a tool for physically testing medical devices with simulated physiologic feedback

MODERNIZATION OF THE MOCK CIRCULATORY LOOP: ADVANCED PHYSICAL MODELING, HIGH PERFORMANCE HARDWARE, AND INCORPORATION OF ANATOMICAL MODELS

A systemic mock circulatory loop plays a pivotal role as the in vitro assessment tool for left heart medical devices. The standard design employed by many research groups dates to the early 1970\u27s, and lacks the acuity needed for the advanced device designs currently being explored. The necessity to update the architecture of this in vitro tool has become apparent as the historical design fails to deliver the performance needed to simulate conditions and events that have been clinically identified as challenges for future device designs. In order to appropriately deliver the testing solution needed, a comprehensive evaluation of the functionality demanded must be understood. The resulting system is a fully automated systemic mock circulatory loop, inclusive of anatomical geometries at critical flow sections, and accompanying software tools to execute precise investigations of cardiac device performance. Delivering this complete testing solution will be achieved through three research aims: (1) Utilization of advanced physical modeling tools to develop a high fidelity computational model of the in vitro system. This model will enable control design of the logic that will govern the in vitro actuators, allow experimental settings to be evaluated prior to execution in the mock circulatory loop, and determination of system settings that replicate clinical patient data. (2) Deployment of a fully automated mock circulatory loop that allows for runtime control of all the settings needed to appropriately construct the conditions of interest. It is essential that the system is able to change set point on the fly; simulation of cardiovascular dynamics and event sequences require this functionality. The robustness of an automated system with incorporated closed loop control logic yields a mock circulatory loop with excellent reproducibility, which is essential for effective device evaluation. (3) Incorporating anatomical geometry at the critical device interfaces; ascending aorta and left atrium. These anatomies represent complex shapes; the flows present in these sections are complex and greatly affect device performance. Increasing the fidelity of the local flow fields at these interfaces delivers a more accurate representation of the device performance in vivo

Cavopulmonary Support for Failing Fontan Patients: Computational and In Vitro Assessment

Congenital heart defects are responsible for the mortality of approximately 300,000 newborn each year. One study in 2010 estimated that over 2 million patients were living with congenital heart defects in the United States. Congenital heart defects have the highest hospitalization cost among other birth defect categories. The damage on the U.S economy in 2013 was estimated $6.1 billion. The most complex and severe form of these defects results in single ventricle physiology. Fortunately, over the last 50 years, these patients have been able to survive into adulthood as a result of three stages of surgeries culminating with Fontan operation. However, Fontan operation as the current ultimate palliation of single ventricle defects results in significant late complications. Fontan patients will eventually develop circulatory failure and are in desperate need of an immediate therapeutic solution. A rightsided device surgically placed in the cavopulmonary pathway could technically substitute the missing sub-pulmonary ventricle by generating a mild pressure boost. However, currently, there is no device specifically designed for this application due to the small market size. On the other hand, off-label use of an arterial pump (originally designed for left side application) for the cavopulmonary support remains challenging. This is because the hemodynamic impact of a ventricular assist device (VAD) implanted on the right circulation of a Fontan patient is not yet clear. Moreover, further research is needed to identify the physiological consequences of two clinically-considered surgical configurations (IVC and full assisted configurations) for the cavopulmonary VAD installation, with full and IVC support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. First objective of this thesis is surgical planning to accurately predict the outcome of cavopulmonary support in failing Fontan patients and findings of this study will help the surgeons in developing coherent clinical strategies for the cavopulmonary support implementation and tuning. Specific objective 2 will investigate the desired operating region for designing a cavopulmonary blood pump that can offer a promising alternative treatment option for a wide range of failing Fontan patients

Bioanalytical Applications of Digital Imaging: Applications to Organ-on-chip and Point-of-care Analysis Systems

Qualitative and quantitative analysis through digital imaging has significant potential in several scientific applications including bioanalytical applications. In this document, the implication of digital imaging to validate and characterize a novel microfluidic organ-on-chip device and establish a point-of-care method to estimate epinephrine concentrations in expired and degraded autoinjectors have been described in chapter 2 and 3 respectively. Chapter 4 includes description of the principle and methodology of strong cation exchange-based immunoassay for oxytocin and β-endorphin. In chapter 2, fabrication of a novel microfluidic organ-on-chip device capable of culturing rodent SCN slices has been discussed. Characterization of the aCSF media droplets and carbogen gas bubbles have also been discussed. Viability of the cultured rodent brain slices using digital imagery through fluorescence calcium imaging and PI/DAPI staining have been reported. In chapter 3, utilization of quantitative smartphone imaging to estimate the concentration of epinephrine in expired and degraded autoinjectors have been described. Actual concentrations of the samples have been established by UHPLC technique. The estimated concentrations of the samples via quantitative smartphone imaging have been reported to possess a strong correlation (r \u3e 0.7) with the actual concentration. Different lighting conditions, distance and angle of camera variations have been explored in chapter 3. Direct immunoassay of relatively small neurotransmitters (~1-5 KDa) through capillary electrophoresis is prone to poor resolution challenge. The principle of using strong cation exchange-based chromatography to carry out such immunoassays have been described in chapter 4. The possible use of crosslinking agents such as sulfo-GMBS and sulfo-SMPB to improve antigen-antibody binding has also been discussed in this chapter. Chapter 5 explores the future directions of improving the rodent slice culture device to accommodate various size and shape of brain slices by chamber geometry and surface energy optimization

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation

LHCb VELO Upgrade: Technical Design Report

The upgraded LHCb VELO silicon vertex detector is a lightweight hybrid pixel detector capable of 40 MHz readout at a luminosity of 2×10^33 cm^−2 s^−1. The track reconstruction speed and precision is enhanced relative to the current VELO detector even at the high occupancy conditions of the upgrade, due to the pixel geometry and a closest distance of approach to the LHC beams of just 5.1 mm for the first sensitive pixel. Cooling is provided by evaporative CO2 circulating in microchannel cooling substrates. The detector contains 41 million 55μ×55μ pixels, read out by the custom developed VeloPix front end ASIC. The detector will start operation together with the rest of the upgraded LHCb experiment after the LHC LS2 shutdown, currently scheduled to end in 2019. This Technical Design Report describes the upgraded VELO system, planned construction and installation, and gives an overview of the expected detector performanc

Twentieth semiannual report to Congress, 1 July - 31 December 1968

Semiannual progress report for NASA programs 196

Aeronautical Engineering: A special bibliography with indexes, Supplement 35, September 1973

This special bibliography lists 614 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1973

Advanced Applications of Rapid Prototyping Technology in Modern Engineering

Rapid prototyping (RP) technology has been widely known and appreciated due to its flexible and customized manufacturing capabilities. The widely studied RP techniques include stereolithography apparatus (SLA), selective laser sintering (SLS), three-dimensional printing (3DP), fused deposition modeling (FDM), 3D plotting, solid ground curing (SGC), multiphase jet solidification (MJS), laminated object manufacturing (LOM). Different techniques are associated with different materials and/or processing principles and thus are devoted to specific applications. RP technology has no longer been only for prototype building rather has been extended for real industrial manufacturing solutions. Today, the RP technology has contributed to almost all engineering areas that include mechanical, materials, industrial, aerospace, electrical and most recently biomedical engineering. This book aims to present the advanced development of RP technologies in various engineering areas as the solutions to the real world engineering problems