Ultrasound deep learning for monitoring of flow-vessel dynamics in murine carotid artery.

Several arterial diseases are closely related with mechanical properties of the blood vessel and interactions of flow-vessel dynamics such as mean flow velocity, wall shear stress (WSS) and vascular strain. However, there is an opportunity to improve the measurement accuracy of vascular properties and hemodynamics by adopting deep learning-based ultrasound imaging for flow-vessel dynamics (DL-UFV). In this study, the DL-UFV is proposed by devising an integrated neural network for super-resolved localization and vessel wall segmentation, and it is also combined with tissue motion estimation and flow measurement techniques such as speckle image velocimetry and speckle tracking velocimetry for measuring velocity field information of blood flow. Performance of the DL-UFV is verified by comparing with other conventional techniques in tissue-mimicking phantoms. After the performance verification, in vivo feasibility is demonstrated in the murine carotid artery with different pathologies: aging and diabetes mellitus (DM). The mutual comparison of flow-vessel dynamics and histological analyses shows correlations between the immunoreactive region and abnormal flow-vessel dynamics interactions. The DL-UFV improves biases in measurements of velocity, WSS, and strain with up to 4.6-fold, 15.1-fold, and 22.2-fold in the tissue-mimicking phantom, respectively. Mean flow velocities and WSS values of the DM group decrease by 30% and 20% of those of the control group, respectively. Mean flow velocities and WSS values of the aging group (34.11 cm/s and 13.17 dyne/cm2) are slightly smaller than those of the control group (36.22 cm/s and 14.25 dyne/cm2). However, the strain values of the aging and DM groups are much smaller than those of the control group (p < 0.05). This study shows that the DL-UFV performs better than the conventional ultrasound-based flow and strain measurement techniques for measuring vascular stiffness and complicated flow-vessel dynamics. Furthermore, the DL-UFV demonstrates its excellent performance in the analysis of the hemodynamic and hemorheological effects of DM and aging on the flow and vascular characteristics. This work provides useful hemodynamic information, including mean flow velocity, WSS and strain with high-resolution for diagnosing the pathogenesis of arterial diseases. This information can be used for monitoring progression and regression of atherosclerotic diseases in clinical practice.

Adaptive hybrid flow measurement of color Doppler and speckle image velocimetry.

Color Doppler (CD) ultrasound has been commonly employed in biomedical field to get hemodynamic information. However, reliable diagnostic evaluation and criteria for vascular diseases may not be provided due to technical limitations of CD, including single-directional measurement, aliasing, and limited imaging conditions. In this study, adaptive hybrid (AH) scheme is proposed to enhance measurement accuracy of conventional CD. It can improve the accuracy of velocity field measurement by replacing erroneous vectors in the measured CD results with the correct vectors obtained from a speckle image velocimetry (SIV) technique. The performance of the proposed AH technique was validated through in vitro experiments for various flow rates and insonation angle conditions, comparing conventional velocimetry techniques. The in vitro experiments demonstrated that the AH technique could measure flow velocity with better accuracy than the CD with bias errors of below 0.7 mm/s. The clinical applicability of the AH was also validated by measuring venous flows at human lower extremity, checking constant volumetric flow rates. Flow rates measured by the AH were maintained along the vein, while the CD and SIV results varied. As a result, the AH can provide improved measurement accuracy without installing a new supplementary equipment. It would be effectively utilized for analyzing flow dynamics and diagnosing valve-related disease.

Deep Learning-Based Super-resolution Ultrasound Speckle Tracking Velocimetry.

Deep ultrasound localization microscopy (deep-ULM) allows sub-wavelength resolution imaging with deep learning. However, the injection of contrast agents (CAs) in deep-ULM is debatable because of their potential risk. In this study, we propose a deep learning-based super-resolution ultrasound (DL-SRU), which employs the concept of deep-ULM and a convolutional neural network. The network is trained with synthetic tracer images to localize positions of red blood cells (RBCs) and reconstruct vessel geometry at high resolution, even for CA-free ultrasound (US) images. The proposed algorithm is validated by comparing the full width at half-maximum values of the vascular profiles reconstructed by other techniques, such as the standard ULM and the US average intensity under in silico and in vitro conditions. RBC localization by DL-SRU is also compared with that by other localization approaches to validate its performance under in vivo condition, especially for veins in the human lower extremity. Furthermore, a two-frame particle tracking velocimetry (PTV) algorithm is applied to DL-SRU localization for accurate flow velocity measurement. The velocity profile obtained by applying the PTV is compared with a theoretical value under in vitro condition to verify its compatibility with the flow measurement modality. The velocity vectors of individual RBCs are obtained to determine the applicability to in vivo conditions. DL-SRU can achieve high-resolution vessel morphology and flow dynamics in vasculature, mapping 110 super-resolved images per second on a standard PC, regardless of various imaging conditions. As a result, the DL-SRU technique is much more robust in localization compared with previous deep-ULM. In addition, the performance of DL-SRU is nearly the same as that of deep-ULM in rapid computational processing and high measurement accuracy. Thus, DL-SRU might become an effective and useful instrument in clinical practice.

Correction: A nature-inspired lubricant-infused surface for sustainable drag reduction.

Correction for 'A nature-inspired lubricant-infused surface for sustainable drag reduction' by Sang Joon Lee et al., Soft Matter, 2019, DOI: 10.1039/c9sm01576k.

A nature-inspired lubricant-infused surface for sustainable drag reduction.

Reduction of frictional drag exerted on submerged marine vehicles results in considerable economic and environmental benefits. A lubricant-infused surface (LIS) inspired by Nepenthes pitcher was introduced as an emerging surface technology for substantial frictional drag reduction. However, the LIS easily loses its drag-reduction ability because the lubricant is easily depleted by shear stresses of external flow. In this study, a new biomimetic LIS with a unique surface topography is proposed to increase the sustainability of the infused lubricant. This biomimetic LIS has re-entrant shaped cavities in the surface, inspired by the mucus secretion and storage systems of loach, hagfish, and seaweed, whose skin can sustain slippery mucus layers even under continuous exposure to harsh seawater flow conditions. The slippery characteristics and enhanced sustainability of the biomimetic LIS were investigated by directly measurement of the slip length and pressure loss in channel flow over the LIS. The frictional drag reduction efficiency of the biomimetic LIS was measured to be approximately 18% compared with the corresponding no-slip surface. Moreover, the excellent sustainability of the biomimetic LIS was demonstrated by comparing the drag-reduction abilities before and after exposure to a high shear flow. The high durability might be attributed to the re-entrant shaped surface topography of the biomimetic LIS. The present results would provide insights into the design of a robust and sustainable LIS for practical drag reduction applications.

Homocysteine-induced peripheral microcirculation dysfunction in zebrafish and its attenuation by L-arginine.

Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter [Formula: see text], where [Formula: see text] and [Formula: see text] represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively. The ratio of the peripheral microcirculation perfusion to the systemic perfusion is largely decreased due to peripheral accumulation of neutrophils, while the systemic perfusion is relatively preserved by increased blood supply from subintestinal vein. Pretreatment with L-arginine attenuates the effects of Hcy on peripheral microcirculation and reduces the peripheral accumulation of neutrophils. Given its convenience, high reproducibility of the observation site, non-invasiveness, and the ease of drug treatment, the present zebrafish model with the proposed parameters will be used as a useful drug screening platform for investigating the pathophysiology of Hcy-induced microvascular diseases.

Hemodynamic characteristics of flow around a deformable stenosis.

Clinical studies reported that some vulnerable stenoses deformed their shape in a blood vessel based on flow condition. However, the effects of shape variation on flow characteristics remain unclear. The flow characteristics are known to affect vulnerable stenosis rupture and fractional flow reserve (FFR) value which has been widely used as a diagnostic tool for stenosis. Vulnerable stenosis rupture occurs when the structural stress exerted on a fibrous cap exceeds its tolerable threshold. The stress magnitude is determined from the spatial distribution of static pressure around the stenosis. In the present study, the static pressure distribution and the FFR value in deformable stenosis were investigated with related other flow characteristics. Two phantom models were fabricated to mimic deformable and nondeformable stenoses using polydimethylsiloxane. The flow characteristics were observed under a steady-flow condition at three Reynolds numbers (Re=500, 1000, 1500) using a particle image velocimetry. The pressure drop across the stenosis models were measured using a pressure sensor to determine effects of shape deformation on FFR value. Shape variations and jet deflections were clearly observed in the deformable stenosis model, and the effective severity of the stenosis increased up to 17.2%. The shape variations of deformable stenosis model increased the static pressure difference at the upstream and downstream sides of the stenosis. The pressure drop across the deformable stenosis model was significantly higher than that of the nondeformable stenosis model. The present results substantiate that stenosis deformability should be carefully considered to diagnose the rupture of vulnerable stenosis.

Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats.

Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.

Variation in wall shear stress in channel networks of zebrafish models.

Physiological functions of vascular endothelial cells (ECs) vary depending on wall shear stress (WSS) magnitude, and the functional change affects the pathologies of various cardiovascular systems. Several in vitro and in vivo models have been used to investigate the functions of ECs under different WSS conditions. However, these models have technical limitations in precisely mimicking the physiological environments of ECs and monitoring temporal variations of ECs in detail. Although zebrafish (Danio rerio) has several strategies to overcome these technical limitations, zebrafish cannot be used as a perfect animal model because applying various WSS conditions on blood vessels of zebrafish is difficult. This study proposes a new zebrafish model in which various WSS can be applied to the caudal vein. The WSS magnitude is controlled by blocking some parts of blood-vessel networks. The accuracy and reproducibility of the proposed method are validated using an equivalent circuit model of blood vessels in zebrafish. The proposed method is applied to lipopolysaccharide (LPS)-stimulated zebrafish as a typical application. The proposed zebrafish model can be used as an in vivo animal model to investigate the relationship between WSS and EC physiology or WSS-induced cardiovascular diseases.

Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish.

Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS) that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV) technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis.

Effect of swirling blood flow on vortex formation at post-stenosis.

Various clinical observations reported that swirling blood flow is a normal physiological flow pattern in various vasculatures. The swirling flow has beneficial effects on blood circulation through the blood vessels. It enhances oxygen transfer and reduces low-density lipoprotein concentration in the blood vessel by enhancing cross-plane mixing of the blood. However, the fluid-dynamic roles of the swirling flow are not yet fully understood. In this study, inhibition of material deposition at the post-stenosis region by the swirling flow was observed. To reveal the underlying fluid-dynamic characteristics, pathline flow visualization and time-resolved particle image velocimetry measurements were conducted. Results showed that the swirling inlet flow increased the development of vortices at near wall region of the post-stenosis, which can suppress further development of stenosis by enhancing transport and mixing of the blood flow. The fluid-dynamic characteristics obtained in this study would be useful for improving hemodynamic characteristics of vascular grafts and stents in which the stenosis frequently occurred. Moreover, the time-resolved particle image velocimetry measurement technique and vortex identification method employed in this study would be useful for investigating the fluid-dynamic effects of the swirling flow on various vascular environments.

Beneficial fluid-dynamic features of pulsatile swirling flow in 45° end-to-side anastomosis.

Although a large number of vascular grafts are surgically implanted annually, approximately 10-15% of these grafts fail in the first year after operation and about 50% are only effective for five to ten years. Surgical implantation of a vascular graft modifies the inherent hemodynamic environment in blood vessels; hence, fluid dynamic characteristics of pathological blood flow are highly related to the performance of the vascular graft. In this study, pathological fluid-dynamic characteristics in a 45° end-to-side anastomosis were experimentally investigated using a particle image velocimetry technique. In particular, the effect of the pulsatile swirling inlet flow in the vascular graft on the improvement of pathological hemodynamic features was systematically investigated. Introducing the pulsatile swirling flow equalizes the asymmetric distribution of wall shear stress and reduces oscillatory shear index and the size of flow separation because the flow disturbs the formation of Dean-type vortices and suppresses secondary flow collision. The fluid dynamic features of the pulsatile swirling flow are expected to be beneficial in designing vascular grafts that can suppress pathological hemodynamic characteristics in the recipient host vessel.

Fluid-dynamic optimal design of helical vascular graft for stenotic disturbed flow.

Although a helical configuration of a prosthetic vascular graft appears to be clinically beneficial in suppressing thrombosis and intimal hyperplasia, an optimization of a helical design has yet to be achieved because of the lack of a detailed understanding on hemodynamic features in helical grafts and their fluid dynamic influences. In the present study, the swirling flow in a helical graft was hypothesized to have beneficial influences on a disturbed flow structure such as stenotic flow. The characteristics of swirling flows generated by helical tubes with various helical pitches and curvatures were investigated to prove the hypothesis. The fluid dynamic influences of these helical tubes on stenotic flow were quantitatively analysed by using a particle image velocimetry technique. Results showed that the swirling intensity and helicity of the swirling flow have a linear relation with a modified Germano number (Gn*) of the helical pipe. In addition, the swirling flow generated a beneficial flow structure at the stenosis by reducing the size of the recirculation flow under steady and pulsatile flow conditions. Therefore, the beneficial effects of a helical graft on the flow field can be estimated by using the magnitude of Gn*. Finally, an optimized helical design with a maximum Gn* was suggested for the future design of a vascular graft.