Transient Performance Analysis of Centrifugal Left Ventricular Assist Devices Coupled With Windkessel Model: Large Eddy Simulations Study on Continuous and Pulsatile Flow Operation.

Computational fluid dynamics (CFD) simulations are widely used to develop and analyze blood-contacting medical devices such as left ventricular assist devices (LVADs). This work presents an analysis of the transient behavior of two centrifugal LVADs with different designs: HeartWare VAD and HeartMate3. A scale-resolving methodology is followed through Large Eddy Simulations, which allows for the visualization of turbulent structures. The three-dimensional (3D) LVAD models are coupled to a zero-dimensional (0D) 2-element Windkessel model, which accounts for the vascular resistance and compliance of the arterial system downstream of the device. Furthermore, both continuous- and pulsatile-flow operation modes are analyzed. For the pulsatile conditions, the artificial pulse of HeartMate3 is imposed, leading to a larger variation of performance variables in HeartWare VAD than in HeartMate3. Moreover, CFD results of pulsatile-flow simulations are compared to those obtained by accessing the quasi-steady maps of the pumps. The quasi-steady approach is a predictive tool used to provide a preliminary approximation of the pulsatile evolution of flow rate, pressure head, and power, by only imposing a speed pulse and vascular parameters. This preliminary quasi-steady solution can be useful for deciding the characteristics of the pulsatile speed law before running a transient CFD simulation, as the former entails a significant reduction in computational cost in comparison to the latter.

Peristaltic pumps adapted for laminar flow experiments enhance in vitro modeling of vascular cell behavior.

Endothelial cells (ECs) are the primary cellular constituent of blood vessels that are in direct contact with hemodynamic forces over their lifetime. Throughout the body, vessels experience different blood flow patterns and rates that alter vascular architecture and cellular behavior. Because of the complexities of studying blood flow in an intact organism, particularly during development, the field has increasingly relied on in vitro modeling of blood flow as a powerful technique for studying hemodynamic-dependent signaling mechanisms in ECs. While commercial flow systems that recirculate fluids exist, many commercially available pumps are peristaltic and best model pulsatile flow conditions. However, there are many important situations in which ECs experience laminar flow conditions in vivo, such as along long straight stretches of the vasculature. To understand EC function under these contexts, it is important to be able to reproducibly model laminar flow conditions in vitro. Here, we outline a method to reliably adapt commercially available peristaltic pumps to study laminar flow conditions. Our proof-of-concept study focuses on 2D models but could be further adapted to 3D environments to better model in vivo scenarios, such as organ development. Our studies make significant inroads into solving technical challenges associated with flow modeling and allow us to conduct functional studies toward understanding the mechanistic role of shear forces on vascular architecture, cellular behavior, and remodeling in diverse physiological contexts.

Continuous versus Pulsatile Flow in 24-Hour Vascularized Composite Allograft Machine Perfusion in Swine: A Pilot Study.

INTRODUCTION: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs. METHODS: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints. RESULTS: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h. CONCLUSIONS: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury.

Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.

BACKGROUND: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. METHODS: This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). RESULTS: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. CONCLUSIONS: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.

Nonlinear hydrodynamic instability and turbulence in pulsatile flow.

Pulsating flows through tubular geometries are laminar provided that velocities are moderate. This in particular is also believed to apply to cardiovascular flows where inertial forces are typically too low to sustain turbulence. On the other hand, flow instabilities and fluctuating shear stresses are held responsible for a variety of cardiovascular diseases. Here we report a nonlinear instability mechanism for pulsating pipe flow that gives rise to bursts of turbulence at low flow rates. Geometrical distortions of small, yet finite, amplitude are found to excite a state consisting of helical vortices during flow deceleration. The resulting flow pattern grows rapidly in magnitude, breaks down into turbulence, and eventually returns to laminar when the flow accelerates. This scenario causes shear stress fluctuations and flow reversal during each pulsation cycle. Such unsteady conditions can adversely affect blood vessels and have been shown to promote inflammation and dysfunction of the shear stress-sensitive endothelial cell layer.

Comparison of hemodynamics and root configurations between remodeling and reimplantation methods for valve-sparing aortic root replacement: a pulsatile flow study.

PURPOSE: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator. METHODS: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18). Valve models were tested at mean pulsatile flow and aortic pressure of 5.0 L/min and 120/80 (100) mmHg, respectively, at 70 beats/min. The forward flow, regurgitation, leakage, backflow rates, valve-closing time, and mean and peak pressure gradient (p-PG) were evaluated. Root configurations were examined using micro-computed tomography (micro-CT). RESULTS: The backflow rate was larger in the RM models than in the RI models (RI: 8.56% ± 0.38% vs. RM: 12.64% ± 0.79%; p < 0.01). The RM-AP and RI models were comparable in terms of the forward flow, regurgitation, backflow rates, p-PG, and valve-closing time. The analysis using a micro-CT showed a larger dilatation of the sinus of the Valsalva in the RM groups than in the RI group (Valsalva: RI, 26.55 ± 0.40 mm vs. RM-AP22, 31.22 ± 0.55 mm [p < 0.05]; RM-AP18, 31.05 ± 0.85 mm [p < 0.05]). CONCLUSIONS: RM with ESA and RI with neo-sinuses showed comparable hemodynamics. ESA to RM reduced regurgitation.

Numerical simulation of effect of hybrid nanofluid on heat transfer and flow of the Newtonian pulsatile blood through 3D occluded artery: Silver and gold nanoparticles.

The study of blood flow in obstructed arteries is a significant focus in computational fluid dynamics, particularly in the field of biomedicine. The primary objective of this research is to investigate the impact of pulsating blood velocity on heat transfer within biological systems, with a specific focus on blood flow in obstructed arteries. To achieve this goal, a comprehensive 3D model representing a straight, constricted blood vessel has been developed. This model incorporates periodic, unsteady, Newtonian blood flow along with the presence of gold and silver nanoparticles. Leveraging the Finite Element Method (FEM), the Navier-Stokes and energy equations have been rigorously solved. Through the investigation, it is aim to shed light on how alterations in the pulsation rate and the volume fraction of nanoparticles influence both temperature distribution and velocity profiles within the system. The present study findings unequivocally highlight that the behavior of pulsatile nanofluid flow significantly impacts the velocity field and heat transfer performance. However, it is imperative to note that the extent of this influence varies depending on the specific volume fractions involved. Specifically, higher volume fractions of nanofluids correlate with elevated velocities at the center of the vessel and decreased velocities near the vessel walls. This pattern also extends to the temperature distribution and heat flux within the vessel, further underscoring the paramount importance of pulsatile flow dynamics in biomedicine and computational fluid dynamics research. Besides, results revealed that the presence of occlusion significantly affects the heat transfer and fluid flow.

A Mathematical Description of the Flow in a Spherical Lymph Node.

The motion of the lymph has a very important role in the immune system, and it is influenced by the porosity of the lymph nodes: more than 90% takes the peripheral path without entering the lymphoid compartment. In this paper, we construct a mathematical model of a lymph node assumed to have a spherical geometry, where the subcapsular sinus is a thin spherical shell near the external wall of the lymph node and the core is a porous material describing the lymphoid compartment. For the mathematical formulation, we assume incompressibility and we use Stokes together with Darcy-Brinkman equation for the flow of the lymph. Thanks to the hypothesis of axisymmetric flow with respect to the azimuthal angle and the use of the stream function approach, we find an explicit solution for the fully developed pulsatile flow in terms of Gegenbauer polynomials. A selected set of plots is provided to show the trend of motion in the case of physiological parameters. Then, a finite element simulation is performed and it is compared with the explicit solution.

Pulsatility hemodynamics during speed modulation of continuous-flow total artificial heart in a chronic in vivo model.

BACKGROUND: The evaluation of pulsatile flow created by the new Cleveland Clinic continuous-flow total artificial heart (CFTAH100), which has a re-designed right impeller and motor, had not been tested in vivo. The purpose of this study was to evaluate the feasibility of pulsatility with the CFTAH100 during the application of pump speed modulation protocols in a chronic animal model. METHODS: A 30-day chronic animal experiment was conducted with a calf. Five pulsatile studies were performed on the alert animal. The mean pump speed was set at 2800 rpm, and modulated sinusoidally within a range of 0 to ± 35% of mean speed, in increments of 5% at 80 beats per minute (bpm). The pressures and pump flow were collected and a pulsatility index (PI) was calculated. RESULTS: The calf was supported with the CFTAH100 without any major complications. The maximum and minimum pump flows changed significantly from baseline in all conditions, while the mean pump flow did not change. All flow pulsatility (FP) readings in all conditions significantly increased from baseline, and the percent modulation (%S) and FP had a strong positive correlation (r = 0.99, p < 0.01). The PI also increased significantly in all conditions (maximum at %S of 35%, 2.2 ± 0.05, p < 0.01), and a positive correlation between %S and PI (r = 0.99, p < 0.01) was observed. CONCLUSION: The CFTAH100 showed the feasibility of creating pulsatile circulation with sinusoidal pump speed modulation.

Effect of pulsatility on shear-induced extensional behavior of Von Willebrand factor.

BACKGROUND: Patients with continuous flow ventricular assist devices (CF-VADs) are at high risk for non-surgical bleeding, speculated to associate with the loss of pulsatility following CF-VAD placement. It has been hypothesized that continuous shear stress causes elongation and increased enzymatic degradation of von Willebrand Factor (vWF), a key player in thrombus formation at sites of vascular damage. However, the role of loss of pulsatility on the unravelling behavior of vWF has not been widely explored. METHODS: vWF molecules were immobilized on the surface of microfluidic devices and subjected to various pulsatile flow profiles, including continuous flow and pulsatile flow of different magnitudes, dQ/dt (i.e., first derivative of flow rate) of pulsatility and pulse frequencies to mimic in vivo shear flow environments with and without CF-VAD support. VWF elongation was observed using total internal reflection fluorescence (TIRF) microscopy. Besides, the vWF level is measured from the patients' blood sample before and after CF-VAD implantation from a clinical perspective. To our knowledge, this work is the first in providing direct, visual observation of single vWF molecule extension under controlled-pulsatile shear flow. RESULTS: Unravelling of vWF (total sample size n ~ 200 molecules) is significantly reduced under pulsatile flow (p < 0.01) compared to continuous flow. An increase in the magnitude of pulsatility further reduces unravelling lengths, while lower frequency of pulsatility (20 vs. 60 pulses per min) does not have a major effect on the maximum or minimum unravelling lengths. Evaluation of CF-VAD patient blood samples (n = 13) demonstrates that vWF levels decreased by ~40% following CF-VAD placement (p < 0.01), which correlates to single-molecule observations from a clinical point of view. CONCLUSIONS: Pulsatile flow reduces unfolding of vWF compared to continuous flow and a lower pulse frequency of 20 pulses/minute yielded comparable vWF unfolding to 60 pulses/minute. These findings could shed light on non-surgical bleeding associated with the loss of pulsatility following CF-VAD placement.

A pre-conditioning protocol of peripheral blood derived endothelial colony forming cells for endothelialization of tissue engineered constructs.

In regenerative medicine, autologous endothelial colony forming cells (ECFCs) bear the greatest potential to be used for surface endothelialization of tissue engineered constructs, as they are easily attainable and possess a high proliferation rate. The aim of this study was to develop a standardized pre-conditioning protocol under dynamic conditions simulating the physiology of human circulation to improve the formation of a flow resistant monolayer of ECFCs and to enhance the antithrombogenicity of the endothelial cells. The main focus of the study was to consequently compare the cellular behavior under a steady laminar flow against a pulsatile flow. Mononuclear cells were isolated out of peripheral blood (PB) buffy coats and plated on uncoated tissue culture flasks in anticipation of guidelines for Advanced Therapy Medicinal Products. ECFCs were identified by typical surface markers such as CD31, CD146 and VE-Cadherin. To explore the effects of dynamic cultivation, ECFCs and human umbilical vein endothelial cells were comparatively cultured under either laminar or pulsatile (1 Hz) flow conditions with different grades of shear stress (5 dyn/cm2versus 20 dyn/cm2). High shear stress of 20 dyn/cm2 led to a significant upregulation of the antithrombotic gene marker thrombomodulin in both cell types, but only ECFCs orientated and elongated significantly after shear stress application forming a confluent endothelial cell layer. The work therefore documents a suitable protocol to pre-condition PB-derived ECFCs for sustainable endothelialization of blood contacting surfaces and provides essential knowledge for future cultivations in bioreactor systems.

Investigating the cause of hemolysis in patients supported by a pulsatile ventricular assist device.

A survey conducted by Abiomed, Inc. revealed that 10 of 60 patients who received ventricular assistance via the AB5000 ventricular assist device (VAD) experienced hemolysis. The present study was conducted to investigate which factors influence hemolysis under pulsatile-flow VADs such as the AB5000. We compared the specificity of the AB5000 and its driving console with those of the NIPRO-VAD and VCT50χ under severe heart failure conditions using a mock circulatory system with a glycerol water solution. We used the mock circuit with bovine blood to confirm which pump conditions were most likely to cause hemolysis. In addition, we measured the shear velocity using particle image velocimetry by analyzing the seeding particle motion for both the AB5000 and NIPRO-VAD under the same conditions as those indicated in the initial experiment. Finally, we analyzed the correlation between negative pressure, exposure time, and hemolysis by continuously exposing fixed vacuum pressures for fixed times in a sealed device injected with bovine blood. Applying higher vacuum pressure to the AB5000 pump yielded a larger minimum inlet pressure and a longer exposure time when the negative pressure was under - 10 mmHg. The plasma-free hemoglobin increased as more negative pressure was driven into the AB5000 pump. Moreover, the negative pressure interacted with the exposure time, inducing hemolysis. This study revealed that negative pressure and exposure time were both associated with hemolysis.

Extracorporeal circulation during on-pump cardiac surgery: An evaluation of the energy equivalent pressure index based on waveforms decomposition in harmonics.

The use of pulsatile perfusion instead of nonpulsatile perfusion during cardiopulmonary bypass continues to be a source of debate. The disagreements among the conclusions of the published studies may be due to different factors: differences in the type of patients included in the studies, differences in the protocol of the studies, and difficulty to quantify the pulsatility of the flow. In the present paper, we propose a quantitative evaluation of Shepard's energy equivalent pressure index, based on the harmonic decomposition of the physiological aortic pressure and flow rate signal. It is thus demonstrated that the surplus energy provided by pulsatile flow remains moderate (of order 10 mm Hg), but that it can be improved by changing the relative shapes of the pressure and flow waves.

Vasoplegia from Continuous Flow Left Ventricular Assist Devices.

PURPOSE OF REVIEW: The contribution of continuous flow left ventricular assist devices (c-LVAD) to vasoplegic syndrome and postoperative outcomes after orthotopic heart transplant (OHT) is contested in the literature. A standardized definition of vasoplegic syndrome (VS) is needed to better recognize and manage vasoplegic shock. RECENT FINDINGS: Vasoplegic syndrome occurs after orthotopic heart transplant more frequently than after other surgeries requiring cardiopulmonary bypass. c-LVADs lead to small vessel endothelial dysfunction and desensitized adrenal receptors; however, their contribution to the development of vasoplegia is debated in clinical studies. Pulsatility may mitigate vascular dysfunction resulting from long-term continuous flow, and should be further explored in the clinical setting when considering risk factors for vasoplegic syndrome. The incidence of vasoplegic syndrome after orthotopic heart transplant is rising with the increasing use of c-LVAD bridge to therapy. Robust clinical studies are needed to advance our understanding and approach to mitigating VS after OHT.

Noninvasive Flow Monitoring in Simple Flow Phantom Using Resistive Strain Sensors.

In this paper, we introduce a monitoring method for flow expansion and contraction in a simple flow phantom based on electrical resistance changes in an epidermal strain sensor attached to the phantom. The flow phantom was fabricated to have a nonflat surface and small modulus that are analogous to human skin. The epidermal sensors made of polydopamine and polyvinyl alcohol show sufficient linearity (R = 0.9969), reproducibility, and self-adhesion properties, as well as high sensitivity to small modulus measurements (<1% tensile strain). Pulsatile flow monitoring experiments were performed by placing the epidermal sensor on the flow phantom and measuring the relative changes in resistance by the heartbeat. Experiments were conducted for three types of vessel diameters (1.5, 2, and 3 mm). In each of the experiments, the vessels were divided into Top, Middle, and Bottom positions. Experiments for each position show that the relative changes in resistance increase proportionally with the diameter of the vessel. The vessels located close to the epidermal layer have greater relative electrical changes. The results were analyzed using the Bernoulli equation and hoop stress formula. This study demonstrates the feasibility of a noninvasive flow monitoring method using a novel resistive strain sensor.

Cu and Cu-SWCNT Nanoparticles' Suspension in Pulsatile Casson Fluid Flow via Darcy-Forchheimer Porous Channel with Compliant Walls: A Prospective Model for Blood Flow in Stenosed Arteries.

The use of experimental relations to approximate the efficient thermophysical properties of a nanofluid (NF) with Cu nanoparticles (NPs) and hybrid nanofluid (HNF) with Cu-SWCNT NPs and subsequently model the two-dimensional pulsatile Casson fluid flow under the impact of the magnetic field and thermal radiation is a novelty of the current study. Heat and mass transfer analysis of the pulsatile flow of non-Newtonian Casson HNF via a Darcy-Forchheimer porous channel with compliant walls is presented. Such a problem offers a prospective model to study the blood flow via stenosed arteries. A finite-difference flow solver is used to numerically solve the system obtained using the vorticity stream function formulation on the time-dependent governing equations. The behavior of Cu-based NF and Cu-SWCNT-based HNF on the wall shear stress (WSS), velocity, temperature, and concentration profiles are analyzed graphically. The influence of the Casson parameter, radiation parameter, Hartmann number, Darcy number, Soret number, Reynolds number, Strouhal number, and Peclet number on the flow profiles are analyzed. Furthermore, the influence of the flow parameters on the non-dimensional numbers such as the skin friction coefficient, Nusselt number, and Sherwood number is also discussed. These quantities escalate as the Reynolds number is enhanced and reduce by escalating the porosity parameter. The Peclet number shows a high impact on the microorganism's density in a blood NF. The HNF has been shown to have superior thermal properties to the traditional one. These results could help in devising hydraulic treatments for blood flow in highly stenosed arteries, biomechanical system design, and industrial plants in which flow pulsation is essential.

Intracranial Pulsatility in Relation to Severity and Progression of Cerebral White Matter Hyperintensities.

BACKGROUND AND PURPOSE: Previous studies suggested an association between increased intracranial arterial pulsatility and the severity of microangiopathic white matter hyperintensities (WMH). However, possible confounders such as age and hypertension were seldomly considered and longitudinal data are lacking. We here aimed to explore whether increased middle cerebral artery pulsatility is associated with baseline severity and progression of cerebral small vessel disease-related WMH in elderly individuals. METHODS: The study population consisted of elderly participants from the community-based ASPS (Austrian Stroke Prevention Study). Baseline and follow-up assessment comprised transcranial Doppler sonography, brain magnetic resonance imaging, and clinical/laboratory examination of vascular risk factors. Pulsatility index on transcranial Doppler sonography was averaged from baseline indices of both middle cerebral arteries and was correlated with baseline WMH severity and WMH progression over a median follow-up period of 5 years in uni- and multivariable analyses. WMH severity was graded according to the Fazekas scale, and WMH load was quantified by semiautomated volumetric assessment. RESULTS: The study cohort comprised 491 participants (mean age: 60.7±6.9 years; female: 48.5%). Pulsatility index was increased in participants with more severe WMH at baseline (P<0.001) but was not associated with WMH progression during follow-up (rs: 0.097, P=0.099). In multivariable analyses, only arterial hypertension remained significantly associated with baseline severity (P=0.04) and progression (P=0.008) of WMH, although transcranial Doppler sonography pulsatility index was not predictive (P>0.1, respectively). CONCLUSIONS: This community-based cohort study of elderly individuals does not support the pulsatility index of the middle cerebral artery on transcranial Doppler sonography as an independent marker of microangiopathic WMH severity and progression over time.

Effect of Natesto on Reproductive Hormones, Semen Parameters and Hypogonadal Symptoms: A Single Center, Open Label, Single Arm Trial.

PURPOSE: To evaluate the effect of short-acting 4.5% nasal testosterone gel (Natesto) on serum testosterone, gonadotropins, total motile sperm count, health related quality of life and sexual function. MATERIALS AND METHODS: This was a single institution, open label, single arm trial conducted between November 2017 and September 2019 at the University of Miami. Men 18 to 55 years old diagnosed with symptomatic hypogonadism (total testosterone less than 300 ng/dl on 2 occasions) were included. Men with azoospermia, vasectomy or a total motile sperm count less than 5 million were excluded. Enrolled patients were treated with Natesto, a short-acting nasal testosterone (125 µl per nostril, 11.0 mg testosterone per dose, TID) for 6 months. RESULTS: In total, 60 men were enrolled in the study. Of these, 44 and 33 patients were evaluated for testosterone at 3 and 6 months, respectively. A total of 31 patients (90.9%) reached a normal testosterone level (greater than 300 ng/dl) at 6 months. Follicle stimulating hormone and luteinizing hormone levels were maintained within the normal range in 81.8% and 72.7% of patients at 6 months, respectively. Total motile sperm count was maintained with total motile sperm count greater than 5 million over the treatment period in 88.4% of men at 3 months and 93.9% at 6 months. There were statistically significant improvements on International Index of Erectile Function sexual desire and overall satisfaction domains at 6 months. CONCLUSIONS: Natesto appears to increase testosterone while maintaining semen parameters in a majority of men. Natesto has the potential to be a safe and effective treatment for men with functional hypogonadism who wish to preserve semen parameters. Long-term studies beyond 6 months are needed before we can safely prescribe nasal testosterone gel for men interested in fertility.

Multiparametric flow analysis using four-dimensional flow magnetic resonance imaging can detect cerebral hemodynamic impairment in patients with internal carotid artery stenosis.

PURPOSE: MRI-based risk stratification should be established to identify patients with internal carotid artery stenosis (ICS) who require further PET or SPECT evaluation. This study assessed whether multiparametric flow analysis using time-resolved 3D phase-contrast (4D flow) MRI can detect cerebral hemodynamic impairment in patients with ICS. METHODS: This retrospective study analyzed 26 consecutive patients with unilateral ICS (21 men; mean age, 71 years) who underwent 4D flow MRI and acetazolamide-stress brain perfusion SPECT. Collateral flow via the Willis ring was visually evaluated. Temporal mean flow volume rate (Net), pulsatile flow volume (ΔV), and pulsatility index (PI) at the middle cerebral artery were measured. Cerebral vascular reserve (CVR) was calculated from the SPECT dataset. Patients were assigned to the misery perfusion group if the CVR was < 10% and to the nonmisery perfusion group if the CVR was ≥ 10%. Parameters showing a significant difference in both groups were statistically evaluated. RESULTS: Affected side ΔV, ratio of affected to contralateral side Net (rNet), and ratio of affected to contralateral side ΔV were significantly correlated to CVR (p = 0.030, p = 0.010, p = 0.015, respectively). Absence of retrograde flow at the posterior communicating artery was observed in the misery perfusion group (p = 0.020). Combined cut-off values of the affected side ΔV (0.18 ml) and rNet (0.64) showed a sensitivity and specificity of 100% and 77.8%, respectively. CONCLUSION: Multiparametric flow analysis using 4D flow MRI can detect misery perfusion by comprehensively assessing blood flow data, including blood flow volume, pulsation, and collateral flow.

Proof of principle of a novel co-pulsating intra-ventricular membrane pump.

In this proof of principle study, we investigated the effectiveness and safety of hemodynamic support with the Intra-Ventricular Membrane Pump (IVMP). The IVMP was implanted into the apex of the left ventricle. Hemodynamic assessment was performed in six ex vivo beating porcine hearts (PhysioHeart platform). The cardiac output (CO), mean arterial pressure (MAP), coronary flow (CF) and pulse pressure (PP) were obtained before and during IVMP support and reported as means ± standard deviations. In two additional visualization experiments, the integrity of the mitral valve was assessed during IVMP support. We found a significant increase of the CO (+1.4 ± 0.2 L/min, P < .001), MAP (+13 ± 6 mm Hg, P = .008), CF (+0.23 ± 0.1 L/min, P = .004), and PP (+15 ± 4 mm Hg, P = .002) during IVMP support, when compared to baseline. No interference of the IVMP with mitral valve function was observed. An increase of premature ventricular complexes (PVC) was observed during support with the IVMP (mean PVC-burden 4.3% vs. 0.7% at baseline), negatively influencing hemodynamic parameters. The IVMP is able to significantly improve hemodynamic parameters in a co-pulsatile fashion, without hampering the function of the mitral valve. These findings provide a basis for future development of a catheter-based IVMP.