Impact of the Spatial Velocity Inlet Distribution on the Hemodynamics of the Thoracic Aorta.

The impact of the distribution in space of the inlet velocity in the numerical simulations of the hemodynamics in the thoracic aorta is systematically investigated. A real healthy aorta geometry, for which in-vivo measurements are available, is considered. The distribution is modeled through a truncated cone shape, which is a suitable approximation of the real one downstream of a trileaflet aortic valve during the systolic part of the cardiac cycle. The ratio between the upper and the lower base of the truncated cone and the position of the center of the upper base are selected as uncertain parameters. A stochastic approach is chosen, based on the generalized Polynomial Chaos expansion, to obtain accurate response surfaces of the quantities of interest in the parameter space. The selected parameters influence the velocity distribution in the ascending aorta. Consequently, effects on the wall shear stress are observed, confirming the need to use patient-specific inlet conditions if interested in the hemodynamics of this region. The surface base ratio is globally the most important parameter. Conversely, the impact on the velocity and wall shear stress in the aortic arch and descending aorta is almost negligible.

High-Versatility Left Ventricle Pump and Aortic Mock Circulatory Loop Development for Patient-Specific Hemodynamic In Vitro Analysis.

The importance of experimental setups able to reproduce cardiac functions was well established in the field of clinical innovations. The mock circulatory loops acquired rising relevance, and the possibility to have a complete reproduction of different and specific fluid dynamic conditions within the setup is pivotal. A system with enough versatility to reproduce the physiologic range of both flows and pressures is required. This study describes the design of a versatile setup composed by a custom pulsatile left ventricular pump system and a 3D-printed mock circulatory loop for the in vitro analysis of a patient-specific case of an aortic complex. The performances of the pump were validated first with a set of test flow profiles. It was demonstrated that the system was able to cover a wide range of aortic and mitral flows. Second, the pump system was inserted within the full mock circulatory loop. A patient-specific case was reproduced, both in terms of flow and pressure profiles. A successful validation of the flow and pressure waveforms was obtained by using patient-specific in vivo data from magnetic resonance analysis.

Mixing Improvement in a T-Shaped Micro-Junction through Small Rectangular Cavities.

The T-shaped micro-junction is among the most used geometry in microfluidic applications, and many design modifications of the channel walls have been proposed to enhance mixing. In this work, we investigate through numerical simulations the introduction of one pair of small rectangular cavities in the lateral walls of the mixing channel just downstream of the confluence region. The aim is to preserve the simple geometry that has contributed to spread the practical use of the T-shaped micro-junction while suggesting a modification that should, in principle, work jointly with the vortical structures present in the mixing channel, further enhancing their efficiency in mixing without significant additional pressure drops. The performance is analyzed in the different flow regimes occurring by increasing the Reynolds number. The cavities are effective in the two highly-mixed flow regimes, viz., the steady engulfment and the periodic asymmetric regimes. This presence does not interfere with the formation of the vortical structures that promote mixing by convection in these two regimes, but it further enhances the mixing of the inlet streams in the near-wall region of the mixing channel without any additional cost, leading to better performance than the classical configuration.

Effects of Uncertainty of Outlet Boundary Conditions in a Patient-Specific Case of Aortic Coarctation.

Computational Fluid Dynamics (CFD) simulations of blood flow are widely used to compute a variety of hemodynamic indicators such as velocity, time-varying wall shear stress, pressure drop, and energy losses. One of the major advances of this approach is that it is non-invasive. The accuracy of the cardiovascular simulations depends directly on the level of certainty on input parameters due to the modelling assumptions or computational settings. Physiologically suitable boundary conditions at the inlet and outlet of the computational domain are needed to perform a patient-specific CFD analysis. These conditions are often affected by uncertainties, whose impact can be quantified through a stochastic approach. A methodology based on a full propagation of the uncertainty from clinical data to model results is proposed here. It was possible to estimate the confidence associated with model predictions, differently than by deterministic simulations. We evaluated the effect of using three-element Windkessel models as the outflow boundary conditions of a patient-specific aortic coarctation model. A parameter was introduced to calibrate the resistances of the Windkessel model at the outlets. The generalized Polynomial Chaos method was adopted to perform the stochastic analysis, starting from a few deterministic simulations. Our results show that the uncertainty of the input parameter gave a remarkable variability on the volume flow rate waveform at the systolic peak simulating the conditions before the treatment. The same uncertain parameter had a slighter effect on other quantities of interest, such as the pressure gradient. Furthermore, the results highlight that the fine-tuning of Windkessel resistances is not necessary to simulate the post-stenting scenario.

A Study on the Effect of Flow Unsteadiness on the Yield of a Chemical Reaction in a T Micro-Reactor.

Despite the very simple geometry and the laminar flow, T-shaped microreactors have been found to be characterized by different and complex steady and unsteady flow regimes, depending on the Reynolds number. In particular, flow unsteadiness modifies strongly the mixing process; however, little is known on how this change may affect the yield of a chemical reaction. In the present work, experiments and 3-dimensional numerical simulations are carried out jointly to analyze mixing and reaction in a T-shaped microreactor with the ultimate goal to investigate how flow unsteadiness affects the reaction yield. The onset of the unsteady asymmetric regime enhances the reaction yield by more than 30%; however, a strong decrease of the yield back to values typical of the vortex regime is observed when the flow undergoes a transition to the unsteady symmetric regime.

Bidirectional biomimetic flow sensing with antiparallel and curved artificial hair sensors.

Background: Flow stimuli in the natural world are varied and contain a wide variety of directional information. Nature has developed morphological polarity and bidirectional arrangements for flow sensing to filter the incoming stimuli. Inspired by the neuromasts found in the lateral line of fish, we present a novel flow sensor design based on two curved cantilevers with bending orientation antiparallel to each other. Antiparallel cantilever pairs were designed, fabricated and compared to a single cantilever based hair sensor in terms of sensitivity to temperature changes and their response to changes in relative air flow direction. Results: In bidirectional air flow, antiparallel cantilever pairs exhibit an axially symmetrical sensitivity between 40 µV/(m s-1) for the lower air flow velocity range (between ±10-20 m s-1) and 80 µV/(m s-1) for a higher air flow velocity range (between ±20-32 m s-1). The antiparallel cantilever design improves directional sensitivity and provides a sinusoidal response to flow angle. In forward flow, the single sensor reaches its saturation limitation, flattening at 67% of the ideal sinusoidal curve which is earlier than the antiparallel cantilevers at 75%. The antiparallel artificial hair sensor better compensates for temperature changes than the single sensor. Conclusion: This work demonstrated the successive improvement of the bidirectional sensitivity, that is, improved temperature compensation, decreased noise generation and symmetrical response behaviour. In the antiparallel configuration, one of the two cantilevers always extends out into the free stream flow, remaining sensitive to directional flow and preserving a sensitivity to further flow stimuli.

Validation of Numerical Simulations of Thoracic Aorta Hemodynamics: Comparison with In Vivo Measurements and Stochastic Sensitivity Analysis.

PURPOSE: Computational fluid dynamics (CFD) and 4D-flow magnetic resonance imaging (MRI) are synergically used for the simulation and the analysis of the flow in a patient-specific geometry of a healthy thoracic aorta. METHODS: CFD simulations are carried out through the open-source code SimVascular. The MRI data are used, first, to provide patient-specific boundary conditions. In particular, the experimentally acquired flow rate waveform is imposed at the inlet, while at the outlets the RCR parameters of the Windkessel model are tuned in order to match the experimentally measured fractions of flow rate exiting each domain outlet during an entire cardiac cycle. Then, the MRI data are used to validate the results of the hemodynamic simulations. As expected, with a rigid-wall model the computed flow rate waveforms at the outlets do not show the time lag respect to the inlet waveform conversely found in MRI data. We therefore evaluate the effect of wall compliance by using a linear elastic model with homogeneous and isotropic properties and changing the value of the Young's modulus. A stochastic analysis based on the polynomial chaos approach is adopted, which allows continuous response surfaces to be obtained in the parameter space starting from a few deterministic simulations. RESULTS: The flow rate waveform can be accurately reproduced by the compliant simulations in the ascending aorta; on the other hand, in the aortic arch and in the descending aorta, the experimental time delay can be matched with low values of the Young's modulus, close to the average value estimated from experiments. However, by decreasing the Young's modulus the underestimation of the peak flow rate becomes more significant. As for the velocity maps, we found a generally good qualitative agreement of simulations with MRI data. The main difference is that the simulations overestimate the extent of reverse flow regions or predict reverse flow when it is absent in the experimental data. Finally, a significant sensitivity to wall compliance of instantaneous shear stresses during large part of the cardiac cycle period is observed; the variability of the time-averaged wall shear stresses remains however very low. CONCLUSIONS: In summary, a successful integration of hemodynamic simulations and of MRI data for a patient-specific simulation has been shown. The wall compliance seems to have a significant impact on the numerical predictions; a larger wall elasticity generally improves the agreement with experimental data.

Non-invasive in vivo detection of peripheral limb ischemia improvement in the rat after adipose tissue-derived stromal cell transplantation.

BACKGROUND: Adipose tissue-derived stromal cells (ADSCs) might help repair ischemic cardiovascular tissue. Their in vivo effects on the bioenergetics and microcirculation of ischemic muscle through a variety of non-invasive techniques was examined. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in 42 rats. One day after femoral artery ligation, 6 rats per group were randomly injected with intramuscularly allogeneic ADSCs (10(6)-10(7)-10(8) cells/ml), conditioned media from ADSC cultures (conditioned media [CM], control), saline (control), allogeneic fibroblasts (10(7) cells/ml, control) or a non-conditioned medium (control). Rats underwent magnetic resonance angiography (MRA), short-time inversion recovery (STIR) edema-weighed imaging, proton MR spectroscopy ((1)H-MRS), thermal infrared imaging (IRI), immunoblotting and immunofluorescence analysis on both hindlimbs for 4 weeks. MRA and STIR documented arterial occlusion and ischemia, respectively. Muscle (1)H-MRS and IRI showed reductions of total creatine (tCr)/water and skin temperature in occluded hind limbs, respectively. At 4 weeks, the ADSC and CM groups had greater recovery of skin temperature and tCr/water in ischemic limbs compared with controls (P<0.01), with increased expression of α-sarcomeric actinin and vascular growth factors, such as hepatocyte growth factor (HGF), increased vessel density (capillaries, arterioles and venules) and less type III collagen. CONCLUSIONS: Allogeneic ADSCs improve ischemic muscle metabolism, increase neovasculogenesis and decrease fibrosis, largely through a paracrine mechanism. (1)H-MRS and IRI are useful tools to monitor attempts at salvaging the ischemic tissues with cell-derived novel therapies.

Scrotal thermoregulatory model and assessment of the impairment of scrotal temperature control in varicocele.

Varicocele is defined as the pathological dilatation of the pampiniform plexus and scrotal veins with venous blood reflux. Varicocele may impair scrotal thermoregulation and spermatogenesis, even when present in asymptomatic forms. In this study, we use the control system theory to model scrotal thermoregulation in response to a standardized cold challenge in order to study the functional thermal impairment secondary to varicocele. The proposed model is based on a homeostatic negative feedback loop, characterized by four distinct parameters, which describe how the control mechanisms are activated and maintained. Thermal infrared images series from 49 young patients suffering from left varicocele and 17 healthy controls were processed. With respect to healthy controls, left varicocele patients presented higher basal scrotal temperature and faster recovery of the left hemiscrotum. The model indicated that varicocele alters local heat exchange processes among cutaneous layers and inner structures. The estimated model parameters help in the assessment of the scrotal thermoregulatory impairment secondary to the disease.

Finger thermoregulatory model assessing functional impairment in Raynaud's phenomenon.

Raynaud's Phenomenon (RP) is a paroxysmal vasospastic disorder of small arteries, pre-capillary arteries, and cutaneous arteriovenous shunts of the extremities, typically induced by cold exposure and emotional stress. RP is either primary (PRP) or secondary to systemic sclerosis. In this study we use Control System Theory to model finger thermoregulatory processes in response to a standardized cold challenge (a diagnostic test routinely performed for differential diagnosis of RP). The proposed model is based on a homeostatic negative feedback loop, characterized by five distinct parameters which describe how the control mechanisms are activated and maintained. Thermal infrared imaging data from 14 systemic sclerosis subjects (SSc), 14 PRP, and 16 healthy control subjects (HCS) were processed. HCS presented the fastest active recovery, with the highest gain. PRP presented the slowest and weakest recovery, mostly due to passive heat exchange with the environment. SSc presented an intermediate behavior, with the longest delay of response onset. The estimated model parameters elucidated the level of functional impairment expressed in the various forms of this disease.