A clinically aligned experimental approach for quantitative characterization of patient-specific cardiovascular models

Recent improvements in computational tools opened the possibility of patient-specific modeling to aid clinicians during diagnosis, treatment, and monitoring. One example is the modeling of blood flow for surgical planning, where modeling can help predict the prognosis. Computational analysis is used to extract hemodynamic information about the case; however, these methods are sensitive to assumptions on blood properties, boundary conditions, and appropriate geometry accuracy. When available, experimental measurements can be used to validate the results and, among the modalities, ultrasound-based methods are suitable due to their relative low cost and non-invasiveness. This work proposes a procedure to create accurate patient-specific silicone replicas of blood vessels and a power Doppler compatible experimental setup able to simulate and measure realistic flow conditions. The assessment of silicone model geometry shows small discrepancies between these and the target geometries (median of surface error lies within 57 µm and 82 μm). Power Doppler measurements were compared against computational fluid dynamics results, showing discrepancies within 10% near the wall. The experimental approach offers a setup to quantify flow in in vitro systems and provide more accurate results where other techniques (e.g., particle image velocimetry and particle tracking velocimetry) have shown limitations due to the interference of the interface

Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles

Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles. Experiments were carried out in a mouse xenograft tumour model for human pancreatic cancer (BxPc-3 cells in male SCID mice). A single dose of 100 μL of oxygen saturated water, oxygen nanobubbles or argon nanobubbles was administered via gavage. Animals were sacrificed 30 minutes post-treatment (3 per group) and expression of hypoxia-inducible-factor-1α (HIF1α) protein measured by real time quantitative polymerase chain reaction and Western blot analysis of the excised tumour tissue. Neither the oxygen saturated water nor argon nanobubbles produced a statistically significant change in HIF1α expression at the transcriptional level. In contrast, a reduction of 75% and 25% in the transcriptional and translational expression of HIF1α respectively (p<0.001) was found for the animals receiving the oxygen nanobubbles. This magnitude of reduction has been shown in previous studies to be commensurate with an improvement in outcome with both radiation and drug-based treatments. In addition, there was a significant reduction in the expression of vascular endothelial growth factor (VEGF) in this group and corresponding increase in the expression of arrest-defective protein 1 homolog A (ARD1A)

Relaxation of Excited Eu(III) Complexes in Cetyltrimethylammonium Bromide Micellar Solutions

The equilibria between pyridine-2,6-dicarboxylate and Eu(III) in H$\text{}_{2}$O or D$\text{}_{2}$O cetyltrimethylammonium bromide micellar solutions at room temperature have been made as a function of the ligand concentration and pH by excitation spectroscopy and emission decay measurements. Formation of the tris-complex is complete at [Eu$\text{}^{3+}$]:[pdc$\text{}^{2-}$] ≥ 1:4 at neutral to slightly alkaline conditions but is incomplete under acidic conditions. The $\text{}^{5}$D$\text{}_{0}$ lifetimes corresponding to the Eu(pdc)$\text{}_{3}^{3-}$ anion is observed to increase on association of the complex with the micellar surface due to exclusion of the solvating molecules from the second co-ordination sphere. Energy transfer in the bulk solution requires the presence of binuclear mixed Eu$\text{}^{3+}$ and Nd(pdc)$\text{}_{3}^{3-}$ complexes or confinement of the Ln(pdc)$\text{}_{3}^{3-}$/Eu$\text{}^{3+}$ on the micelle surface. Energy transfer from the Eu(pdc)$\text{}_{3}^{3-}$ anion is inefficient in the bulk solution

Molecular Dynamics Simulations of Liquid Condensed to Liquid Expanded Transitions in DPPC Monolayers

We have investigated the phase behavior of DPPC (dipalmitoylphosphatidylcholine) monolayers at the water-air interface using molecular dynamics simulations, where the phospholipids and the water molecules are modeled atomistically. We report pressure-area isotherms in the interval of 273-310 K. Our results show evidence for a liquid condensed (LC) to liquid expanded (LE) phase transition and indicate that ordered condensed phases call nucleate from a starting disordered phase on a time scale of approximately 50 ns. The existence of the phase transition is confirmed with structural analyses of the phospholipid pair correlation functions and of the monolayer thickness. We find that the change in the monolayer thickness associated with the LC-LE transition is largely due to a shortening of the hydrocarbon chains, with little modification in the average tilt angle of the choline head group. This result is compatible with recent sum frequency spectroscopy experiments, Which Concluded that the transition Occurs without major changes in the orientation of the head group with respect to the monolayer plane. The dependence of the simulated pressure-area isotherms oil temperature, in particular, the reduction in width of the coexistence plateau with increasing temperature, is consistent with published experimental pressure-area isotherms

Single bubble acoustic characterization and stability measurement of adherent microbubbles

This article examines how the acoustic and stability characteristics of single lipid-shelled microbubbles (MBs) change as a result of adherence to a target surface. For individual adherent and non-adherent MBs, the backscattered echo from a narrowband 2-MHz, 90-kPa peak negative pressure interrogation pulse was obtained. These measurements were made in conjunction with an increasing amplitude broadband disruption pulse. It was found that, for the given driving frequency, adherence had little effect on the fundamental response of an MB. Examination of the second harmonic response indicated an increase of the resonance frequency for an adherent MB: resonance radius increasing of 0.3 ± 0.1 μm for an adherent MB. MB stability was seen to be closely related to MB resonance and gave further evidence of a change in the resonance frequency due to adherence

The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm Treatment with Flow-Diverter Stents

BACKGROUND AND PURPOSE: Treatment of intracranial bifurcation aneurysms with flow-diverter stents can lead to caliber changes of the distal vessels in a subacute phase. This study aims to evaluate whether local anatomy and flow disruption induced by flow-diverter stents are associated with vessel caliber changes in intracranial bifurcations. MATERIALS AND METHODS: Radiologic images and demographic data were acquired for 25 patients with bifurcation aneurysms treated with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were used to evaluate if anatomic data and caliber changes could be linked. Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized and patient-specific anatomies to evaluate flow changes induced by flow-diverter stents in the jailed vessel. RESULTS: Statistical analysis identified a marked correspondence between asymmetric bifurcation and caliber change. Symmetry ratios were lower for cases showing narrowing or subacute occlusion (medium daughter vessel diameter ratio = 0.59) compared with cases with posttreatment caliber conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid dynamics analysis in idealized and patient-specific anatomies showed that wall shear stress in the jailed vessel was more affected when flow-diverter stents were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected when deployed in symmetric anatomies (diameter ratio ∼1.00). CONCLUSIONS: Anatomic data analysis showed statistically significant correspondence between caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P < .001). Similarly, computational fluid dynamics results showed the highest impact on hemodynamics when flow-diverter stents are deployed in asymmetric bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress fields. Further research and clinical validation are necessary to identify all elements involved in vessel caliber changes after flow-diverter stent procedures