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Cressman, E.

Publications and source records attributed to Cressman, E..

2 recordsLinked to original sources

Quantitative Comparison of 3D-1D Vascular Coupling Models: Lateral Average versus Sphere of Influence Methods

Computational models coupling one-dimensional vascular networks with three-dimensional tissue domains are widely used for predicting blood flow distribution in tumor perfusion, drug delivery, and therapeutic planning. Two prominent coupling paradigms have emerged: the Lateral Average Model (LAM) which implements distributed transmural exchange via a vessel wall conductivity parameter{gamma} (m Pa-1 s-1), and the Sphere of Influence (SOI) model, which employs localized terminal coupling via a source sphere radius{varepsilon} (m). Despite their broad application, systematic quantitative comparisons of their parametric behavior and predictive equivalence remain lacking. We compare LAM and SOI in 3D-1D simulations on a benchmark vascular network and a porcine liver study with a hepatic arterial network reconstructed from CT arteriography. Across a benchmark vascular network under three sink configurations, the LAM net flow rate rose smoothly with{gamma} and saturated at a plateau, while the SOI net flow rate increased with{varepsilon} without saturating; as a result, global-flow equivalence between the two formulations exists only for particular boundary geometries, and not at all within the tested parameter range for one of the three configurations examined. Despite this partial agreement in total flow, the two models diverged substantially in regional perfusion: in a porcine hepatic arterial network reconstructed from CT arteriography, SOI predicted stable perfusion fractions to two regions of interest across its full tested parameter range, whereas LAM predictions for the same regions varied several-fold with vessel wall permeability and, at low permeability, could invert which region received more flow. These results indicate that the choice of coupling model has limited consequence for predicted total organ flow but substantial consequence for predicted local drug delivery, and we provide guidance for selecting between the two formulations depending on the clinical or research question being asked. Author SummaryWhen doctors plan treatments for liver cancer, they often rely on computer simulations to predict how blood flows through the liver and how well a drug will reach the tumor. These simulations depend on mathematical models that describe how blood moves from vessels into surrounding tissue. Two commonly used approaches exist for building these models, but researchers have generally chosen between them based on habit or convenience rather than on a principled understanding of how their predictions differ. In this work, we directly compared these two approaches, one that spreads blood exchange continuously along the vessel wall, and one that delivers blood from the vessel tips into a surrounding spherical zone, using both a simple test network and a realistic pig liver reconstructed from medical imaging. We found that the two approaches can agree on the total amount of blood reaching the liver, but disagree substantially on where that blood goes within the tissue. This distinction matters enormously for treatment planning: a model that predicts the right total blood flow but delivers it to the wrong region of the liver could lead to an inaccurate forecast of drug concentration at the tumor site. Our results provide practical guidance for researchers on which approach to use depending on what information is available and what question is being asked.

biophysics↗

Cirrhosis and Inflammation Regulates CYP3A4 Mediated Chemoresistance in Vascularized Hepatocellular Carcinoma-on-a-chip

Understanding the effects of inflammation and cirrhosis on the regulation of drug metabolism during the progression of hepatocellular carcinoma (HCC) is critical for developing patient-specific treatment strategies. In this work, we created novel three-dimensional vascularized HCC-on-a-chips (HCCoC), composed of HCC, endothelial, stellate, and Kupffer cells tuned to mimic normal or cirrhotic liver stiffness. HCC inflammation was controlled by tuning Kupffer macrophage numbers, and the impact of cytochrome P450-3A4 (CYP3A4) was investigated by culturing HepG2 HCC cells transfected with CYP3A4 to upregulate expression from baseline. This model allowed for the simulation of chemotherapeutic delivery methods such as intravenous injection and transcatheter arterial chemoembolization (TACE). We showed that upregulation of metabolic activity, incorporation of cirrhosis and inflammation, increase vascular permeability due to upregulated inflammatory cytokines leading to significant variability in chemotherapeutic treatment efficacy. Specifically, we show that further modulation of CYP3A4 activity of HCC cells by TACE delivery of doxorubicin provides an additional improvement to treatment response and reduces chemotherapy-associated endothelial porosity increase. The HCCoCs were shown to have utility in uncovering the impact of the tumor microenvironment (TME) during cancer progression on vascular properties, tumor response to therapeutics, and drug delivery strategies. Statement of SignificanceRegulation of drug metabolism during the cancer progression of hepatocellular carcinoma (HCC) can be influential to develop personalized treatment strategies. We created novel vascularized hepatocellular carcinoma-chip (HCCoC) composed of tunable collagen and four main liver-specific cell lines to be used as a preclinical tool. In this model, we found cancer evolution states such as inflammation and cirrhosis increases vascular permeability progressively as a result of increased inflammatory cytokines. Furthermore, delivery of doxorubicin only with embolization improved treatment efficacy by decreasing CYP3A4 activity, which can modulate treatment outcome. Overall, we found different disease states can be influential on CYP3A4, thus its targeting can improve HCC treatment outcome.

bioengineering↗