International Journal of Non-linear Mechanics, Jun 1, 2017
In this paper, we study the fully developed gravity-driven flow of granular materials between two... more In this paper, we study the fully developed gravity-driven flow of granular materials between two inclined planes. We assume that the granular materials can be represented by a modified form of the second-grade fluid where the viscosity depends on the shear rate and volume fraction and the normal stress coefficients depend on the volume fraction. We also propose a new isotropic (spherical) part of the stress tensor which can be related to the compactness of the (rigid) particles. This new term ensures that the rigid solid particles cannot be compacted beyond a point, namely when the volume fraction has reached the critical/maximum packing value. The numerical results indicate that the newly proposed stress tensor has an obvious and physically meaningful effects on both the velocity and the volume fraction fields.
Thrombosis under high-shear conditions is mediated by the mechanosensitive blood glycoprotein von... more Thrombosis under high-shear conditions is mediated by the mechanosensitive blood glycoprotein von Willebrand Factor (vWF). vWF unfolds in response to strong flow gradients and facilitates rapid recruitment of platelets in flowing blood. While the thrombogenic effect of vWF is well recognized, its conformational response in complex flows has largely been omitted from numerical models of thrombosis. We recently presented a continuum model for the unfolding of vWF, where we represented vWF transport and its flow-induced conformational change using convection-diffusion-reaction equations. Here, we incorporate the vWF component into our multi-constituent model of thrombosis, where the local concentration of stretched vWF amplifies the deposition rate of free-flowing platelets and reduces the shear cleaning of deposited platelets. We validate the model using three benchmarks: in vitro model of atherothrombosis, a stagnation point flow, and the PFA-100 ® , a clinical blood test commonly used for screening for von Willebrand Disease (vWD). The simulations reproduced the key aspects of vWF-mediated thrombosis observed in these experiments, such as the thrombus location, thrombus growth dynamics, and the effect of blocking platelet-vWF interactions. The PFA-100 ® simulations closely matched the reported occlusion times for normal blood and several hemostatic deficiencies, namely, thrombocytopenia, vWD Type 1, and vWD Type 3. Overall, this multi-constituent model of thrombosis enables macro-scale 3-D simulations of thrombus formation in complex geometries over a wide range of shear rates and accounts for qualitative and quantitative hemostatic deficiencies in patient blood. SIGNIFICANCE Application of numerical models of thrombosis to the problem of arterial clot formation revealed that to achieve platelet aggregation at pathologically high shear rates, platelet adhesion rates or adhesion strength must be increased to account for platelet-vWF interactions. Many existing models have correlated platelet adhesion parameters to local shear rate or elongation rate, but not both. vWF, on the other hand, exhibits different responses in simple shear and extensional flow, with distinct thresholds for unfolding and conformational hysteresis effects. The multi-constituent model of thrombosis presented in this work features our continuum model of vWF unfolding and demonstrates its utility in predicting macro-scale thrombus formation in high-shear conditions. The vWF component could also be adapted to other numerical models of thrombosis.
International Journal of Engineering Science, Feb 1, 2020
This study was undertaken to develop a numerical/computational simulation of von Willebrand Facto... more This study was undertaken to develop a numerical/computational simulation of von Willebrand Factor (vWF)-mediated platelet shear activation and deposition in an idealized stenosis. Blood is treated as a multi-constituent mixture comprised of a linear fluid component and a porous solid component (thrombus). Chemical and biological species involved in coagulation are modeled using a system of coupled convection-reaction-diffusion (CRD) equations. This study considers the cumulative effect of shear stress (history) on platelet activation. The vWF activity is modeled as an enhancement function for the shear stress accumulation and is related to the experimentally-observed unfolding rate of vWF. A series of simulations were performed in an idealized stenosis in which the predicted platelets deposition agreed well with previous experimental observations spatially and temporally, including the reduction of platelet deposition with decreasing expansion angle. Further simulation indicated a direct relationship between vWF-mediated platelet deposition and degree of stenosis. Based on the success with these benchmark simulations, it is hoped that the model presented here may provide additional insight into vWF-mediated thrombosis and prove useful for the development of more hemo-compatible blood-wetted devices in the future.
Journal of Biomedical Materials Research Part A, May 6, 2014
Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect... more Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined platelet deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize platelet deposition, we sought to perform such an evaluation. Fluorescently labeled platelets mixed with human RBC ghosts were perfused across 6 opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al 2 O 3), 2methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 sec −1. Ti6Al4V had significantly increased platelet deposition relative to MPC-Ti6Al4V, Al 2 O 3 , YZTP, and ZTA at both wall shear rates (P <0.01). For all test surfaces, increasing the wall shear rate produced a trend of decreased platelet adhesion. The described system can be a utilized as a tool for comparative analysis of candidate blood-contacting materials with acute blood contact.
Bulletin of the American Physical Society, Nov 24, 2015
Based on the Sorenson's model of thrombus formation[1, 2], a new mathematical model describing th... more Based on the Sorenson's model of thrombus formation[1, 2], a new mathematical model describing the process of thrombus growth is developed. In this model the blood is treated as a Newtonian fluid, and the transport and reactions of the chemical and biological species are modeled using CRD (convection-reaction-diffusion) equations. A computational fluid dynamic (CFD) solver for the mathematical model is developed using the libraries of OpenFOAM. Applying the CFD solver, several representative benchmark problems are studied: rapid thrombus growth in vivo by injecting Adenosine diphosphate (ADP) using iontophoretic method and thrombus growth in rectangular microchannel with a crevice which usually appears as a joint between components of devices and often becomes nidus of thrombosis. Very good agreements between the numerical and the experimental results validate the model and indicate its potential to study a host of complex and practical problems in the future, such as thrombosis in blood pumps and artificial lungs. 1. Sorensen, E.N., et al., Computational simulation of platelet deposition and activation: I. Model development and properties.
Clinical decision support tools (DSTs) are computational systems that aid healthcare decisionmaki... more Clinical decision support tools (DSTs) are computational systems that aid healthcare decisionmaking. While effective in labs, almost all these systems failed when they moved into clinical practice. Healthcare researchers speculated it is most likely due to a lack of user-centered HCI considerations in the design of these systems. This paper describes a field study investigating how clinicians make a heart pump implant decision with a focus on how to best integrate an intelligent DST into their work process. Our findings reveal a lack of perceived need for and trust of machine intelligence, as well as many barriers to computer use at the point of clinical decision-making. These findings suggest an alternative perspective to the traditional use models, in which clinicians engage with DSTs at the point of making a decision. We identify situations across patients' healthcare trajectories when decision supports would help, and we discuss new forms it might take in these situations.
medRxiv (Cold Spring Harbor Laboratory), Apr 26, 2023
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
ASAIO and the entire artificial organs community lost a truly remarkable inventor, visionary, col... more ASAIO and the entire artificial organs community lost a truly remarkable inventor, visionary, colleague, and friend with the passing of Ken Butler on December 13, 2018 (Figure 1). Ken's professional career, like the man himself, was remarkable. For 13 years, Ken was a project engineer/rocket scientist at Aerojet Liquid Rocket Company (Rancho Cordova, CA), responsible for developing the main engine for the Saturn V rocket that sent three Apollo astronauts to the moon. This is where he developed his acumen in turbo-pump design and led him to become project engineer for the Artificial Heart Team at Aerojet. In 1982 Ken and members of his team formed Nimbus Inc. in Rancho Cordova, California, where he and his team secured major government contracts for pioneering thermally-powered artificial hearts and left ventricular assist devices (LVADs). Together with their clinical partner, the Cleveland Clinic Foundation, they were contracted by National Heart Lung and Blood Institute (NHLBI) to develop an electro-hydraulic LVAD, a fully implantable LVAD, and a total artificial heart (TAH). Ken's successes over the years in securing NHLBI grants and contracts paved the way for Nimbus' clinical introduction of two breakthrough blood pumps that revolutionized the field of mechanical circulatory support (MCS): the Hemopump™ in 1988 and the "Axipump" which later became the HeartMate II (HM II) in 2003. Our "connection" with Ken Butler began for one of us (H.S.B.) in 1977 at the First Annual Contractors Conference sponsored by the Devices and Technology Branch of NHLBI. At that meeting, and subsequent Contractors Conferences, Ken reported masterfully on his thermal energy systems for MCS and TAH/LVAD technologies under development, which established him as one of the lead investigators in the field. It was also very obvious how respected and liked Ken was by all in the field, including his competitors for NHLBI funding in the TAH and LVAD programs.
Current risk stratification models to predict outcomes after a left ventricular assist device (LV... more Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012-2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort) , we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3 and 12 months post implant according to disease severity (IM profiles), device type (axial v. centrifugal) and strategy (bridge to transplantation or destination therapy). 15% (n=308) were categorized as IM Profile 1, 36% (n=752) as Profile 2, 33% (n=672) as Profile 3 and 15% (n=311) as Profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
PediaFlow is a miniature mixed-flow ventricular assist device for neonates and toddlers. PediaFlo... more PediaFlow is a miniature mixed-flow ventricular assist device for neonates and toddlers. PediaFlow has a fully magnetically levitated rotor which improves biocompatibility, but the increased length of the rotor creates a long annular passage where fluid energy is lost. Therefore, a set of helical stator blades was proposed immediately after the impeller stage to remove the swirling flow and recover the dynamic head as static pressure. Automated computational fluid dynamics (CFD) shape optimization of the stator blades was performed to maximize pressure recovery at the operating point of 1.5 LPM and 16,000 RPM. Additionally, the effect on hemolysis and thrombogenicity were assessed using numerical modeling. The optimization algorithm favored fewer blades of greater length over a larger number of short blades. The ratio of wrap angle to axial length emerged as a key constraint to ensure the viability of a design. The best design had 2 blades and generated 73 mmHg of pressure recovery in an isolated stage. When reintroduced to the CFD simulation of the complete flow path, the added stator stage increased the pump head by 46% and improved the pump efficiency from 21.9% to 25.7% at the selected operating point. Automated CFD shape optimization combined with in silico evaluation of hemocompatibility can be an effective tool for exploring design choices and informing early development process.
Significance: Longitudinal tracking of hemodynamic changes in the breast has shown potential for ... more Significance: Longitudinal tracking of hemodynamic changes in the breast has shown potential for neoadjuvant chemotherapy (NAC) outcome prediction. Spatial frequency domain imaging (SFDI) could be suitable for frequent monitoring of shallow breast tumors, but strong sensitivity to superficial absorbers presents a challenge. Aim: We investigated the efficacy of a two-layer SFDI inverse model that accounts for varying melanin concentration in the skin to improve discrimination of optical properties of deep tissue of the breast. Approach: Hemodynamic changes in response to localized breast compression were measured in 13 healthy volunteers using a handheld SFDI device. Epidermis optical thickness was determined based on spectral fitting of the model output and used to calculate subcutaneous optical properties. Results: Optical properties from a homogeneous model yielded physiologically unreasonable absorption and scattering coefficients for highly pigmented volunteers. The two-layer model compensated for the effect of melanin and yielded properties in the expected range for healthy breast. Extracted epidermal optical thickness was higher for higher Fitzpatrick types. Compression induced a decrease in total hemoglobin consistent with tissue blanching. Conclusions: The handheld SFDI device and two-layer model show potential for imaging hemodynamic responses that potentially could help predict efficacy of NAC in patients of varying skin tones.
International Journal of Non-linear Mechanics, Jun 1, 2017
In this paper, we study the fully developed gravity-driven flow of granular materials between two... more In this paper, we study the fully developed gravity-driven flow of granular materials between two inclined planes. We assume that the granular materials can be represented by a modified form of the second-grade fluid where the viscosity depends on the shear rate and volume fraction and the normal stress coefficients depend on the volume fraction. We also propose a new isotropic (spherical) part of the stress tensor which can be related to the compactness of the (rigid) particles. This new term ensures that the rigid solid particles cannot be compacted beyond a point, namely when the volume fraction has reached the critical/maximum packing value. The numerical results indicate that the newly proposed stress tensor has an obvious and physically meaningful effects on both the velocity and the volume fraction fields.
Thrombosis under high-shear conditions is mediated by the mechanosensitive blood glycoprotein von... more Thrombosis under high-shear conditions is mediated by the mechanosensitive blood glycoprotein von Willebrand Factor (vWF). vWF unfolds in response to strong flow gradients and facilitates rapid recruitment of platelets in flowing blood. While the thrombogenic effect of vWF is well recognized, its conformational response in complex flows has largely been omitted from numerical models of thrombosis. We recently presented a continuum model for the unfolding of vWF, where we represented vWF transport and its flow-induced conformational change using convection-diffusion-reaction equations. Here, we incorporate the vWF component into our multi-constituent model of thrombosis, where the local concentration of stretched vWF amplifies the deposition rate of free-flowing platelets and reduces the shear cleaning of deposited platelets. We validate the model using three benchmarks: in vitro model of atherothrombosis, a stagnation point flow, and the PFA-100 ® , a clinical blood test commonly used for screening for von Willebrand Disease (vWD). The simulations reproduced the key aspects of vWF-mediated thrombosis observed in these experiments, such as the thrombus location, thrombus growth dynamics, and the effect of blocking platelet-vWF interactions. The PFA-100 ® simulations closely matched the reported occlusion times for normal blood and several hemostatic deficiencies, namely, thrombocytopenia, vWD Type 1, and vWD Type 3. Overall, this multi-constituent model of thrombosis enables macro-scale 3-D simulations of thrombus formation in complex geometries over a wide range of shear rates and accounts for qualitative and quantitative hemostatic deficiencies in patient blood. SIGNIFICANCE Application of numerical models of thrombosis to the problem of arterial clot formation revealed that to achieve platelet aggregation at pathologically high shear rates, platelet adhesion rates or adhesion strength must be increased to account for platelet-vWF interactions. Many existing models have correlated platelet adhesion parameters to local shear rate or elongation rate, but not both. vWF, on the other hand, exhibits different responses in simple shear and extensional flow, with distinct thresholds for unfolding and conformational hysteresis effects. The multi-constituent model of thrombosis presented in this work features our continuum model of vWF unfolding and demonstrates its utility in predicting macro-scale thrombus formation in high-shear conditions. The vWF component could also be adapted to other numerical models of thrombosis.
International Journal of Engineering Science, Feb 1, 2020
This study was undertaken to develop a numerical/computational simulation of von Willebrand Facto... more This study was undertaken to develop a numerical/computational simulation of von Willebrand Factor (vWF)-mediated platelet shear activation and deposition in an idealized stenosis. Blood is treated as a multi-constituent mixture comprised of a linear fluid component and a porous solid component (thrombus). Chemical and biological species involved in coagulation are modeled using a system of coupled convection-reaction-diffusion (CRD) equations. This study considers the cumulative effect of shear stress (history) on platelet activation. The vWF activity is modeled as an enhancement function for the shear stress accumulation and is related to the experimentally-observed unfolding rate of vWF. A series of simulations were performed in an idealized stenosis in which the predicted platelets deposition agreed well with previous experimental observations spatially and temporally, including the reduction of platelet deposition with decreasing expansion angle. Further simulation indicated a direct relationship between vWF-mediated platelet deposition and degree of stenosis. Based on the success with these benchmark simulations, it is hoped that the model presented here may provide additional insight into vWF-mediated thrombosis and prove useful for the development of more hemo-compatible blood-wetted devices in the future.
Journal of Biomedical Materials Research Part A, May 6, 2014
Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect... more Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined platelet deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize platelet deposition, we sought to perform such an evaluation. Fluorescently labeled platelets mixed with human RBC ghosts were perfused across 6 opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al 2 O 3), 2methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 sec −1. Ti6Al4V had significantly increased platelet deposition relative to MPC-Ti6Al4V, Al 2 O 3 , YZTP, and ZTA at both wall shear rates (P <0.01). For all test surfaces, increasing the wall shear rate produced a trend of decreased platelet adhesion. The described system can be a utilized as a tool for comparative analysis of candidate blood-contacting materials with acute blood contact.
Bulletin of the American Physical Society, Nov 24, 2015
Based on the Sorenson's model of thrombus formation[1, 2], a new mathematical model describing th... more Based on the Sorenson's model of thrombus formation[1, 2], a new mathematical model describing the process of thrombus growth is developed. In this model the blood is treated as a Newtonian fluid, and the transport and reactions of the chemical and biological species are modeled using CRD (convection-reaction-diffusion) equations. A computational fluid dynamic (CFD) solver for the mathematical model is developed using the libraries of OpenFOAM. Applying the CFD solver, several representative benchmark problems are studied: rapid thrombus growth in vivo by injecting Adenosine diphosphate (ADP) using iontophoretic method and thrombus growth in rectangular microchannel with a crevice which usually appears as a joint between components of devices and often becomes nidus of thrombosis. Very good agreements between the numerical and the experimental results validate the model and indicate its potential to study a host of complex and practical problems in the future, such as thrombosis in blood pumps and artificial lungs. 1. Sorensen, E.N., et al., Computational simulation of platelet deposition and activation: I. Model development and properties.
Clinical decision support tools (DSTs) are computational systems that aid healthcare decisionmaki... more Clinical decision support tools (DSTs) are computational systems that aid healthcare decisionmaking. While effective in labs, almost all these systems failed when they moved into clinical practice. Healthcare researchers speculated it is most likely due to a lack of user-centered HCI considerations in the design of these systems. This paper describes a field study investigating how clinicians make a heart pump implant decision with a focus on how to best integrate an intelligent DST into their work process. Our findings reveal a lack of perceived need for and trust of machine intelligence, as well as many barriers to computer use at the point of clinical decision-making. These findings suggest an alternative perspective to the traditional use models, in which clinicians engage with DSTs at the point of making a decision. We identify situations across patients' healthcare trajectories when decision supports would help, and we discuss new forms it might take in these situations.
medRxiv (Cold Spring Harbor Laboratory), Apr 26, 2023
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
ASAIO and the entire artificial organs community lost a truly remarkable inventor, visionary, col... more ASAIO and the entire artificial organs community lost a truly remarkable inventor, visionary, colleague, and friend with the passing of Ken Butler on December 13, 2018 (Figure 1). Ken's professional career, like the man himself, was remarkable. For 13 years, Ken was a project engineer/rocket scientist at Aerojet Liquid Rocket Company (Rancho Cordova, CA), responsible for developing the main engine for the Saturn V rocket that sent three Apollo astronauts to the moon. This is where he developed his acumen in turbo-pump design and led him to become project engineer for the Artificial Heart Team at Aerojet. In 1982 Ken and members of his team formed Nimbus Inc. in Rancho Cordova, California, where he and his team secured major government contracts for pioneering thermally-powered artificial hearts and left ventricular assist devices (LVADs). Together with their clinical partner, the Cleveland Clinic Foundation, they were contracted by National Heart Lung and Blood Institute (NHLBI) to develop an electro-hydraulic LVAD, a fully implantable LVAD, and a total artificial heart (TAH). Ken's successes over the years in securing NHLBI grants and contracts paved the way for Nimbus' clinical introduction of two breakthrough blood pumps that revolutionized the field of mechanical circulatory support (MCS): the Hemopump™ in 1988 and the "Axipump" which later became the HeartMate II (HM II) in 2003. Our "connection" with Ken Butler began for one of us (H.S.B.) in 1977 at the First Annual Contractors Conference sponsored by the Devices and Technology Branch of NHLBI. At that meeting, and subsequent Contractors Conferences, Ken reported masterfully on his thermal energy systems for MCS and TAH/LVAD technologies under development, which established him as one of the lead investigators in the field. It was also very obvious how respected and liked Ken was by all in the field, including his competitors for NHLBI funding in the TAH and LVAD programs.
Current risk stratification models to predict outcomes after a left ventricular assist device (LV... more Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012-2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort) , we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3 and 12 months post implant according to disease severity (IM profiles), device type (axial v. centrifugal) and strategy (bridge to transplantation or destination therapy). 15% (n=308) were categorized as IM Profile 1, 36% (n=752) as Profile 2, 33% (n=672) as Profile 3 and 15% (n=311) as Profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
PediaFlow is a miniature mixed-flow ventricular assist device for neonates and toddlers. PediaFlo... more PediaFlow is a miniature mixed-flow ventricular assist device for neonates and toddlers. PediaFlow has a fully magnetically levitated rotor which improves biocompatibility, but the increased length of the rotor creates a long annular passage where fluid energy is lost. Therefore, a set of helical stator blades was proposed immediately after the impeller stage to remove the swirling flow and recover the dynamic head as static pressure. Automated computational fluid dynamics (CFD) shape optimization of the stator blades was performed to maximize pressure recovery at the operating point of 1.5 LPM and 16,000 RPM. Additionally, the effect on hemolysis and thrombogenicity were assessed using numerical modeling. The optimization algorithm favored fewer blades of greater length over a larger number of short blades. The ratio of wrap angle to axial length emerged as a key constraint to ensure the viability of a design. The best design had 2 blades and generated 73 mmHg of pressure recovery in an isolated stage. When reintroduced to the CFD simulation of the complete flow path, the added stator stage increased the pump head by 46% and improved the pump efficiency from 21.9% to 25.7% at the selected operating point. Automated CFD shape optimization combined with in silico evaluation of hemocompatibility can be an effective tool for exploring design choices and informing early development process.
Significance: Longitudinal tracking of hemodynamic changes in the breast has shown potential for ... more Significance: Longitudinal tracking of hemodynamic changes in the breast has shown potential for neoadjuvant chemotherapy (NAC) outcome prediction. Spatial frequency domain imaging (SFDI) could be suitable for frequent monitoring of shallow breast tumors, but strong sensitivity to superficial absorbers presents a challenge. Aim: We investigated the efficacy of a two-layer SFDI inverse model that accounts for varying melanin concentration in the skin to improve discrimination of optical properties of deep tissue of the breast. Approach: Hemodynamic changes in response to localized breast compression were measured in 13 healthy volunteers using a handheld SFDI device. Epidermis optical thickness was determined based on spectral fitting of the model output and used to calculate subcutaneous optical properties. Results: Optical properties from a homogeneous model yielded physiologically unreasonable absorption and scattering coefficients for highly pigmented volunteers. The two-layer model compensated for the effect of melanin and yielded properties in the expected range for healthy breast. Extracted epidermal optical thickness was higher for higher Fitzpatrick types. Compression induced a decrease in total hemoglobin consistent with tissue blanching. Conclusions: The handheld SFDI device and two-layer model show potential for imaging hemodynamic responses that potentially could help predict efficacy of NAC in patients of varying skin tones.
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