Regional assessment of vascular morphology and hemodynamics: methodology and evaluation for abdominal aortic aneurysms after endovascular repair.

Abdominal aortic aneurysm is a deadly disease that can be treated with different endovascular devices that will distinctly alter the aortic morphology. Computational methods can be used to understand the effect of anatomical changes on aortic hemodynamics. We propose a standardized method to assess morphological and hemodynamic changes of the abdominal aorta through the longitudinal axis of the vessel. Patient-specific CFD simulations were used to quantify these changes for two different endografts before and after surgery. Differences in cross-sectional area, blood pressure, peak blood velocity, wall shear stress, and retrograde blood flow were accurately evidenced with the proposed methodology.

Quantitative assessment of the conjunctival microcirculation using a smartphone and slit-lamp biomicroscope.

PURPOSE: The conjunctival microcirculation is a readily-accessible vascular bed for quantitative haemodynamic assessment and has been studied previously using a digital charge-coupled device (CCD). Smartphone video imaging of the conjunctiva, and haemodynamic parameter quantification, represents a novel approach. We report the feasibility of smartphone video acquisition and subsequent haemodynamic measure quantification via semi-automated means. METHODS: Using an Apple iPhone 6 s and a Topcon SL-D4 slit-lamp biomicroscope, we obtained videos of the conjunctival microcirculation in 4 fields of view per patient, for 17 low cardiovascular risk patients. After image registration and processing, we quantified the diameter, mean axial velocity, mean blood volume flow, and wall shear rate for each vessel studied. Vessels were grouped into quartiles based on their diameter i.e. group 1 (<11 µm), 2 (11-16 µm), 3 (16-22 µm) and 4 (>22 µm). RESULTS: From the 17 healthy controls (mean QRISK3 6.6%), we obtained quantifiable haemodynamics from 626 vessel segments. The mean diameter of microvessels, across all sites, was 21.1µm (range 5.8-58 µm). Mean axial velocity was 0.50mm/s (range 0.11-1mm/s) and there was a modestly positive correlation (r 0.322) seen with increasing diameter, best appreciated when comparing group 4 to the remaining groups (p < .0001). Blood volume flow (mean 145.61pl/s, range 7.05-1178.81pl/s) was strongly correlated with increasing diameter (r 0.943, p < .0001) and wall shear rate (mean 157.31 s-1, range 37.37-841.66 s-1) negatively correlated with increasing diameter (r - 0.703, p < .0001). CONCLUSIONS: We, for the first time, report the successful assessment and quantification of the conjunctival microcirculatory haemodynamics using a smartphone-based system.

Fluid-structure interaction assessment of blood flow hemodynamics and leaflet stress during mitral regurgitation.

The aim of this study is to simulate the Mitral Regurgitation (MR) disease progression from mild to severe intensity. A Fluid Structure Interaction (FSI) model was developed to extract the hemodynamic parameters of blood flow in mitral regurgitation (MR) during systole. A two-dimensional (2D) geometry of the mitral valve was built based on the data resulting from Magnetic Resonance Imaging (MRI) dimensional measurements. The leaflets were assumed to be elastic. Using COMSOL software, the hemodynamic parameters of blood flow including velocity, pressure, and Von Mises stress contours were obtained by moving arbitrary Lagrange-Euler mesh. The results were obtained for normal and MR cases. They showed the effects of the abnormal distance between the leaflets on the amount of returned flow. Furthermore, the deformation of the leaflets was measured during systole. The results were found to be consistent with the relevant literature.

Photoplethysmography for the Assessment of Haemorheology.

Haemorheology has been long identified as an early biomarker of a wide range of diseases, especially cardiovascular diseases. This study investigates for the first time the suitability of Photoplethysmography (PPG) as a non-invasive diagnostic method for haemorheological changes. The sensitivity of both PPG components (AC and DC) to changes in haemorheology were rigorously investigated in an in vitro experimental setup that mimics the human circulation. A custom-made reflectance PPG sensor, a pressure transducer and an ultrasonic Doppler flowmeter were used to map changes in flow dynamics and optical responses in an arterial model. The study investigated the effect of shear rates by varying fluid pumping frequencies using 4 set-points and the effect of clot formation using a chemical trigger. Both PPGAC amplitudes and PPGDC levels showed significant (p < 0.001) changes during the increase in shear rates and an immediate change after thromboplastin activation. The findings highlight that PPG has the potential to be used as a simple non-invasive method for the detection of blood characteristics, including disaggregation, radial migration and cross-linking fibrin formations. Such capability will enable the assessment of the effects of clotting-activators and anticoagulants (including non-pharmacological methods) and might aid in the early non-invasive assessment of cardiovascular pathologies.

Assessment of Influences of Stenoses in Right Carotid Artery on Left Carotid Artery Using Wall Stress Marker.

Purpose. Atherosclerosis is a diseased condition of blood vessel. It causes partial blockage in lumen of vessel and affects hemodynamic of localized flowing blood. Complex geometries like region of bifurcation also affects hemodynamic to a larger extent. Complexity further increases in presence of stenoses at region of bifurcation. Such morphological change in vessel largely affects parent as well as corresponding sister and daughter vessels. In this paper, complexity in hemodynamic of blood in pair of carotid arteries (left and right carotid arteries) is evaluated in presence of stenoses at basilar segment of right artery in three-dimensional domain using reconstructed tomographic images of patient. Methods. Transient information of blood flow is obtained using four-dimensional phase-contrast MRI technique. Haematocrit component of blood at diseased condition is considered using Power Law and Quemada model. Numerical techniques are used to solve pressure-coupled governing equations of flowing blood. Results. Dysfunctions of endothelial cells near the wall are characterised by evaluating shear stress markers. Wall shear stress and its gradient based and harmonic based descriptors are calculated over complete geometry during one cardiac cycle. Conclusion. Internal branch of left carotid artery and external branch of right carotid artery are found prone to secondary stenoses in presence of primary stenoses at basilar segment of right carotid artery.

A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces.

The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates.

Computational simulation of carotid stenosis and flow dynamics based on patient ultrasound data - A new tool for risk assessment and surgical planning.

PURPOSE: There is nowadays extensive experimental and computational investigation on the pathophysiology of atherosclerosis, searching correlations between its focal nature and local hemodynamic environment. The goal of this work is to present a methodology for patient-specific hemodynamics study of the carotid artery bifurcation based on the use of ultrasound (US) morphological and blood flow velocity patient data. MATERIALS/METHODS: Subject-specific studies were performed for two patients, using a developed finite element code. Geometrical models were obtained from the acquisition of longitudinal and sequential cross-sectional ultrasound images and boundary conditions from Doppler velocity measurements at the common carotid artery. RESULTS: There was a good agreement between ultrasound imaging data and computational simulated results. For a normal and a stenosed carotid bifurcation the velocity, wall shear stress (WSS) and WSS descriptors analysis illustrated the extremely complex hemodynamic behavior along the cardiac cycle. Different patterns were found, associated with morphology and hemodynamic patient-specific conditions. High values of time-averaged WSS (TAWSS) were found at stenosis site and for both patients TAWSS fields presented low values within areas of high oscillating shear index and relative residence time values, corresponding to recirculation zones. CONCLUSION: Simulated hemodynamic parameters were able to capture the disturbed flow conditions in a normal and a stenosed carotid artery bifurcation, which play an important role in the development of local atherosclerotic plaques. Computational simulations based on clinic US might help improving diagnostic and treatment management of carotid atherosclerosis.

Effect of variation in hemorheology between human and animal blood on the binding efficacy of vascular-targeted carriers.

Animal models are extensively used to evaluate the in vivo functionality of novel drug delivery systems (DDS). However, many variations likely exist in vivo between the animals and human physiological environment that significantly alter results obtained with animal models relative to human system. To date, it is not clear if the variation in hemorheology and hemodynamics between common animal and human models affect the functionality of DDS. This study investigates the role of hemorheology of humans and various animal models in dictating the binding efficiency of model vascular-targeted carriers (VTCs) to the wall in physiological blood flows. Specifically, the adhesion of sLe(A)-coated nano- and micro-spheres to inflamed endothelial cells monolayers were conducted via a parallel plate flow chamber assay with steady and disturbed red blood cells (RBCs)-in-buffer and whole blood flows of common animal models. Our results suggest that the ratio of carrier size to RBC size dictate particle binding in blood flow. Additionally, the presence of white blood cells affects the trend of particle adhesion depending on the animal species. Overall, this work sheds light on some deviation in VTC vascular wall interaction results obtained with in vivo animal experimentation from expected outcome and efficiency in vivo in human.

Thrombolytic effects of the snake venom disintegrin saxatilin determined by novel assessment methods: a FeCl3-induced thrombosis model in mice.

Saxatilin, a novel disintegrin purified and cloned from the venom of the Korean snake Gloydius saxatilis, strongly inhibits activation and aggregation of platelets. Glycoprotein (GP) IIb/IIIa receptor antagonists can resolve thrombus, so saxatilin might also have thrombolytic effects. We investigated the thrombolytic effects of saxatilin in mice using a ferric chloride-induced carotid arterial thrombosis model. Thrombotic occlusion and thrombus resolution were evaluated quantitatively by measuring blood flow in the carotid artery with an ultrasonic flow meter and calculating the degree of flow restoration on a minute-by-minute basis; results were confirmed by histological examination. Saxatilin dissolved thrombi in a dose-dependent manner. Saxatilin at 5 mg/kg restored blood flow to baseline levels. As saxatilin dose increased, time to recanalization decreased. A bolus injection of 10% of a complete dose with continuous infusion of the remaining dose for 60 minutes resulted in effective recanalization without reocclusion. The thrombolytic effect of saxatilin was also demonstrated in vitro using platelet aggregometry by administering saxatilin in preformed thrombi. Bleeding complications were observed in 2 of 71 mice that received saxatilin. Fibrin/fibrinogen zymography and platelet aggregometry studies indicated that saxatilin does not have fibrinolytic activity, but exerted its action on platelets. Integrin-binding assays showed that saxatilin inhibited multiple integrins, specifically α2bß3 (GP IIb/IIIa), α5ß1, αvß3, αvß1, and αvß5, which act on platelet adhesion/aggregation. Saxatilin inhibited multiple integrins by acting on platelets, and was safe and effective in resolving thrombi in mice.

[SKF-index as an indicator of biological age of hemostasis and blood vessels in children and adults in norm and pathology].

A novel noninvasive method of an assessment of the hemostasis system and the vascular walls functioning is proposed. This method is based on the methodology of dynamic light scattering (DLS). New index SKF, which is derived from the previously established relationship between the intravascular mobility of the erythrocytes and the biological age, has been introduced. We demonstrated that the degree of the severity of the diseases correlates with the SKF index. More specifically, an increased value of the SKF index was found for the groups with cardio-vascular, oncological diseases and diabetes mellitus. In addition we provided evidences that the SKF index depends on the blood and plasma viscosity related to activity stage of the hemostasis system as well as on the functioning of the vascular walls.

Numerical and experimental assessment of turbulent kinetic energy in an aortic coarctation.

The turbulent blood flow through an aortic coarctation in a 63-year old female patient was studied experimentally using magnetic resonance imaging (MRI), and numerically using computational fluid dynamics (CFD), before and after catheter intervention. Turbulent kinetic energy (TKE) was computed in the numerical model using large eddy simulation and compared with direct in vivo MRI measurements. Despite the two totally different methods to obtain TKE values, both quantitative and qualitative results agreed very well. The results showed that even though both blood flow rate and Reynolds number increased after intervention, total turbulent kinetic energy levels decreased in the coarctation. Therefore, the use of the Reynolds number alone as a measure of turbulence in cardiovascular flows should be used with caution. Furthermore, the change in flow field and kinetic energy were assessed, and it was found that before intervention a jet formed in the throat of the coarctation, which impacted the arterial wall just downstream the constriction. After intervention the jet was significantly weaker and broke up almost immediately, presumably resulting in less stress on the wall. As there was a good agreement between measurements and numerical results (the increase and decrease of integrated TKE matched measurements almost perfectly while peak values differed by approximately 1mJ), the CFD results confirmed the MRI measurements while at the same time providing high-resolution details about the flow. Thus, this preliminary study indicates that MR-based TKE measurements might be useful as a diagnostic tool when evaluating intervention outcome, while the detailed numerical results might be useful for further understanding of the flow for treatment planning.

Computational flow dynamics and preclinical assessment of a novel hemodialysis catheter.

We examined flow characteristics and recirculation of a novel dialysis catheter with helically contoured lumens, which optimize the vectors of blood entering and leaving the device. Computational flow dynamics were used to measure shear stress, residence time (RT), Platelet Lysis Index (PLI), and recirculation of the study catheter, termed the VectorFlow catheter, compared with the Palindrome catheter. Bench and animal models were used to measure recirculation compared with other dialysis catheter designs. The VectorFlow catheter was associated with an 18% reduction in mean shear stress compared with the Palindrome catheter, at 13.6 and 16.6 Pa, respectively. Low PLI was seen with the VectorFlow (PLI = 0.019) and Palindrome (PLI = 0.015) catheters. The VectorFlow catheter was associated with a % RT >0.030 seconds of 1.2%, compared to 0.9% for the Palindrome. Calculated recirculation of the VectorFlow, Palindrome, and step-tip catheter designs in reversed position were 1.2 × 10(-4) %, 0.039%, and 13.6%, respectively. In vitro, the VectorFlow catheter had no detectable recirculation (0%) compared to 7.3-9.5% with the Palindrome at flow rates of 400-600 ml/minute. In vivo, the VectorFlow catheter had no detectable recirculation, compared to 6.7-12% for the Palindrome. The VectorFlow catheter was associated with an absence of detectable recirculation with favorable flow dynamics.

In vivo multispectral photoacoustic and photothermal flow cytometry with multicolor dyes: a potential for real-time assessment of circulation, dye-cell interaction, and blood volume.

Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo detection of circulating tumor cells and bacteria targeted by nanoparticles. Here, we propose multispectral PAFC with multiple dyes having distinctive absorption spectra as multicolor PA contrast agents. As a first step of our proof-of-concept, we characterized high-speed PAFC capability to monitor the clearance of three dyes (Indocyanine Green [ICG], Methylene Blue [MB], and Trypan Blue [TB]) in an animal model in vivo and in real time. We observed strong dynamic PA signal fluctuations, which can be associated with interactions of dyes with circulating blood cells and plasma proteins. PAFC demonstrated enumeration of circulating red and white blood cells labeled with ICG and MB, respectively, and detection of rare dead cells uptaking TB directly in bloodstream. The possibility for accurate measurements of various dye concentrations including Crystal Violet and Brilliant Green were verified in vitro using complementary to PAFC photothermal (PT) technique and spectrophotometry under batch and flow conditions. We further analyze the potential of integrated PAFC/PT spectroscopy with multiple dyes for rapid and accurate measurements of circulating blood volume without a priori information on hemoglobin content, which is impossible with existing optical techniques. This is important in many medical conditions including surgery and trauma with extensive blood loss, rapid fluid administration, and transfusion of red blood cells. The potential for developing a robust clinical PAFC prototype that is safe for human, and its applications for studying the liver function are further highlighted.

Noninvasive assessment of wall-shear rate and vascular elasticity using combined ARFI/SWEI/spectral Doppler imaging system.

The progression of atherosclerotic disease is a complex process believed to be a function of the localized mechanical properties and hemodynamic loading associated with the arterial wall. It is hypothesized that measurements of cardiovascular stiffness and wall-shear rate (WSR) may provide important information regarding vascular remodeling, endothelial function and the growth of soft lipid-filled plaques that could help a clinician better predict the occurrence of clinical events such as stroke. Two novel ARFI based imaging techniques, combined on-axis/off-axis ARFI/Spectral Doppler Imaging (SAD-SWEI) and Gated 2D ARFI/Spectral Doppler Imaging (SAD-Gated), were developed to form co-registered depictions of B-mode echogenicity, ARFI displacements, ARF-excited transverse wave velocity estimates and estimates ofwall-shear rate throughout the cardiac cycle. Implemented on a commercial ultrasound scanner, the developed techniques were evaluated in tissue-mimicking and steady-state flow phantoms and compared with conventional techniques, other published study results and theoretical values. Initial in vivo feasibility of the method is demonstrated with results obtained from scanning the carotid arteries of five healthy volunteers. Cyclic variations over the cardiac cycle were observed in on-axis displacements, off-axis transverse-wave velocities and wall-shear rates.

Numerical modeling of stress in stenotic arteries with microcalcifications: a parameter sensitivity study.

As a follow-up to the work presented in Wenk et al. (2010, "Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation," ASME J. Biomech. Eng., 132, p. 091011), a formal sensitivity study was conducted in which several model parameters were varied. The previous work only simulated a few combinations of the parameters. In the present study, the fibrous cap thickness, longitudinal position of the region of microcalcifications, and volume fraction of microcalcifications were varied over a broader range of values. The goal of the present work is to investigate the effects of localized regions of microcalcifications on the stress field of atherosclerotic plaque caps in a section of carotid artery. More specifically, the variations in the magnitude and location of the maximum circumferential stress were assessed for a range of parameters using a global sensitivity analysis method known as Sobol' indices. The stress was calculated by performing finite element simulations of three-dimensional fluid-structure interaction models, while the sensitivity indices were computed using a Monte Carlo scheme. The results indicate that cap thickness plays a significant role in the variation in the magnitude of the maximum circumferential stress, with the sensitivity to volume fraction increasing when the region of microcalcification is located at the shoulder. However, the volume fraction played a larger role in the variation in the location of the maximum circumferential stress. This matches the finding of the previous study (Wenk et al., 2010, "Numerical Modeling of Stress in Stenotic Arteries With Microcalcifications: A Micromechanical Approximation," ASME J. Biomech. Eng., 132, p. 091011), which indicates that the maximum circumferential stress always shifts to the region of microcalcification.

One-arm maximal strength training improves work economy and endurance capacity but not skeletal muscle blood flow.

Maximal strength training with a focus on maximal mobilization of force in the concentric phase improves endurance performance that employs a large muscle mass. However, this has not been studied during work with a small muscle mass, which does not challenge convective oxygen supply. We therefore randomized 23 adult females with no arm-training history to either one-arm maximal strength training or a control group. The training group performed five sets of five repetitions of dynamic arm curls against a near-maximal load, 3 days a week for 8 weeks. This training increased maximal strength by 75% and improved rate of force development during both strength and endurance exercise, suggesting that each arm curl became more efficient. This coincided with a 17-18% reduction in oxygen cost at standardized submaximal workloads (work economy), and a 21% higher peak oxygen uptake and 30% higher peak load during maximal arm endurance exercise. Blood flow assessed by Doppler ultrasound in the axillary artery supplying the working biceps brachii and brachialis muscles could not explain the training-induced adaptations. These data suggest that maximal strength training improved work economy and endurance performance in the skeletal muscle, and that these effects are independent of convective oxygen supply.