Vascular Bifurcations Research Articles

Red Blood Cell‐resolved 3D Computational Modeling of Blood Flow in Physiologically Realistic Microvascular Networks

Microvascular networks represent geometrically complex architecture due to constantly bifurcating and merging vessels. Moreover, blood vessels are not necessarily straight, and often highly winding. Mathematical models of blood flow in such networks have treated these vessels as 1D straight segments neglecting the geometric complexity and details. These models also do not consider the deformation and flow of individual red blood cell, and instead use empirical relations to prescribe blood viscosity and red blood cell distribution at a vascular bifurcation. As such, these models cannot predict hemodynamic variations over short time and length scales. To overcome this limitation, we have recently developed a high‐fidelity 3D, first‐principle based, fluid‐‐structure interaction model of blood flow in physiologically realistic microvascular networks. The model retains the exact geometric details of the vasculature, e.g., 3D nature of the blood vessels and bifurcations, and vessel curvature. Deformation and flow of each individual red blood cell as they flow through the vessels are exactly modeled. The model is based on the minimal assumptions: it does not assume any empirical viscosity law or bifurcation law; rather, these laws are predicted by the model. The model provides microscale details of hemodynamic quantities that are not readily available in experiments, and cannot be predicted by the traditional 1D network models, such as wall shear stress gradient and time‐dependent red blood cell partitioning at bifurcations.Of particular interest is the role of red blood cell deformability on hematocrit distribution in the networks. Cell deformability is known to reduce in many diseases, such as sickle cell disease, malaria and diabetes. By using in vivo images of retinal microvasculature, we have performed simulation of network blood flow under varying cell deformability in such networks. The model shows that altered cell deformability significantly changes the cell distribution in the network, and subsequently the flow resistance in vessels. While some vessels show a significant increase in hematocrit, some show a significant decrease. Such a redistribution of hematocrit for diseased red blood cells may have a significant impact on tissue oxygen delivery. The simulation results are used to mechanistically explain the observed redistribution of hematocrit and vascular resistance.Support or Funding InformationFunded by NSF

Vascular bifurcation mapping with photoacoustic microscopy

The early detection of microvascular changes in cancer diagnosis is needed in the clinic. A change in the vascular bifurcation density is a biomarker for the sprouting activity. Here, Optical-Resolution PhotoAcoustic Microscopy is used for quantitative vascular bifurcation mapping in 2D after the creation of Virtual Tubes out of Bifurcations. In stacks of OR-PAM images of the hemoglobin distribution, bifurcations become tubes and are selected by the 3D tubeness filter. These fast analyses will be compared to a classical approach and are easier to implement for functional analysis of the vascular bifurcation density in healthy and diseased tissues.

Risk Factors for Asymptomatic Intracranial Small Aneurysm Rupture Determined by Electrocardiographic-Gated 4D Computed Tomographic (CT) Angiography.

BackgroundTo study the risk predictors of intracranial asymptomatic small aneurysm rupture by electrocardiographic (ECG)-gated 4D-CT angiography (4D-CTA).Material/MethodsA total of 168 patients with intracranial aneurysms <7 mm who underwent 4D-CTA examinations were retrospectively analyzed and divided into a ruptured group and an unruptured group. The original scanning data of all cases were reconstructed to obtain 20 groups of data in 5% time intervals in the cardiac cycle. After processing with 3D workstation software, 20 sets of images and dynamic images were achieved. The morphological characteristics and clinical features of the 2 groups of aneurysms were analyzed through univariate analysis, then logistic regression analysis was performed for the meaningful indicators. Finally, the optimum diagnostic cut-off point was calculated by ROC curve analysis.ResultsUnivariate analysis showed that sex, smoking history, vascular bifurcation point, pulsation point appearance, aneurysm height, aspect ratio (AR), and size ratio (SR) were significantly different (P<0.05) between the ruptured group and unruptured group. Multivariate regression analysis indicated that the pulsation points (OR=8.188, 95% CI: 3.984–17.198) and high SR values (OR=5.325, 95% CI: 1.503–18.867) were independent predictors of asymptomatic small aneurysm rupture. When the SR value was higher than 1.65, the area below the ROC curve was 0.723, the diagnostic sensitivity was 75%, and the specificity was 80%.ConclusionsThe occurrence of pulsation points and SR values >1.65 were independent predictors for the rupture of asymptomatic small intracranial aneurysms <7 mm in diameter.

Retinal Mosaicking with Vascular Bifurcations Detected on Vessel Mask by a Convolutional Network.

Mosaicking of retinal images is potentially useful for ophthalmologists and computer-aided diagnostic schemes. Vascular bifurcations can be used as features for matching and stitching of retinal images. A fully convolutional network model is employed to segment vascular structures in retinal images to detect vascular bifurcations. Then, bifurcations are extracted as feature points on the vascular mask by a robust and efficient approach. Transformation parameters for stitching can be estimated from the correspondence of vascular bifurcations. The proposed feature detection and mosaic method is evaluated on retinal images of 14 different eyes, 62 retinal images. The proposed method achieves a considerably higher average recall rate of matching for paired images compared with speeded-up robust features and scale-invariant feature transform. The running time of our method was also lower than other methods. Results produced by the proposed method superior to that of AutoStitch, photomerge function in Photoshop cs6 and ICE, demonstrate that accurate matching of detected vascular bifurcations could lead to high-quality mosaic of retinal images.

Dynamic Response of Stents in Vascular Systems: Development of an Adaptive Model to Study the Effect of Stent Placement on Aneurysmal and Occlusive Arterial Disease in Various Anatomical Configuration

Introduction: Modelling of the vascular system is complex due to the non-linear nature of the vascular tree and the effect of pathology upon it. This is complicated by self-regulation to maintain perfusion across the vascular system and bifurcation within the arterial tree. Stents deployed within the vascular system remove the system ability to adapt through the stented areas. Methods: We developed a model of dynamic response incorporating wave reflection and fluid solid interaction in a blood vessel containing a stent and a system of stenting. Using partial differential equation formulation including the extension of the Korteweg flow model we have studied transmission/reflection problems. Three-dimensional simulations were constructed using Comsol Multiphysics Software. Results: The model required development of an elastic shell for the arterial component based on published literature. The stent is modelled by a periodic skeleton structure within the elastic shell of the artery. In order for fluid solid interaction to be studied the model incorporate pulsatility, frequency, time, elastic properties of the wall, the periodicity of the stents and pressure. The model demonstrates the determinant of wave/pulse reflection is the periodicity of the stented structure. The stiffer the stent the higher frequency waves are reflected. Interlinking of periodic stents reduced reflection of waves at low frequency. Reflections were increased where multiple stents are inserted. Bifurcations have an increase on wave reflection, and this is multiplied with overlapping or interconnecting periodic stents. Conclusion: Modelling of biological system can be achieved through fluid solid interaction equations. When considering complex systems where periodic and/or multiple stents have been inserted the model must cover the interactions between the stents to accurately predict the effect on the vascular tree. Periodic stenting leads to reflection of waves as they are transmitted along healthy and unhealthy blood vessels and these reflections may lead to unforeseen alterations in blood flow depending upon the configuration of the stents and the anatomy into which they are placed. Disclosure: Nothing to disclose

A Bifurcated Vascular Channel Construction Method based on Diploic Vein Characteristics

In skull bone tissue engineering, cells do not easily survive and proliferate in the scaffold because of the lack of nutrient transport channels. To address these problems, a vascular design and fabrication method based on human skull diploic vein characteristics was proposed. The skull sample was scanned by micro-CT, and the 3D model was constructed by Avizo. By analyzing the characteristics of the diploic vein, the vascular centerline model, path model, taper model and bifurcation model were proposed. Two vascular network examples were constructed by iteration of the bifurcation unit. The mold method of constructing vascular scaffolds embedded within the bionic channels was proposed. The scaffold material is PDMS, and the surface was coated with collagen. The Human Umbilical Vein Endothelial Cells (HUVECs) were planted into the lumen of the channels for 7 days in vitro and found to be able to proliferate. The cells cultured for three days were fluorescently stained, and it was found that the cells were well attached to the surfaces of the lumen. This vascular design and fabrication process can lay a foundation for vascularization in bone tissue engineering.

A framework for hierarchical division of retinal vascular networks

Human retinal vascular network plays an important role in ophthalmology diagnosis. For example, in the diagnosis of ophthalmology, the severity of the disease has a direct correlation with the lesion location, in the sense that the closer the lesion area is to the optic disk, the higher will be the severity of the disease. If a framework is able to provide the hierarchical structure of the retinal vascular network, then the severity of disease can be quantified by leveraging the hierarchical characteristics of vessels in the vicinity of the lesion location. Thus, in this paper, an executable framework is recommended for the hierarchical division of the retinal vascular networks. Specifically, a supervised method based on deep neural network is used for retinal blood vessel segmentation. A graph-based method is also applied to generate vascular trees from the segmented retinal vessels. As part of our proposed approach, we present two algorithms: the potential landmark detection algorithm (PLDA) is used to identify the bifurcations and crossings; and the adaptive hierarchical classification algorithm (AHCA) is used in the hierarchical characteristics classification of vascular bifurcations. By classifying the hierarchical characteristics of vascular bifurcation, the hierarchical characteristics of the vessel segments containing these bifurcations are identified. Thus, the hierarchical division of retinal vascular network is realized. When applied to two publicly available datasets, DRIVE and STARE, the proposed framework achieves an accurate rate of 98.99% and sensitivity rate of 92.17%.

The cell-free layer in simulated microvascular networks

In the microcirculation, a plasma layer forms near the vessel walls that is free of red blood cells (RBCs). This region, often termed as the cell-free layer (CFL), plays important haemorheological and biophysical roles, and has been the subject of extensive research. Many previous studies have considered the CFL development in single, isolated vessels that are straight tubes or channels, as well as in isolated bifurcations and mergers. In the body, blood vessels are typically winding and sequentially bifurcate into smaller vessels or merge to form larger vessels. Because of this geometric complexity, the CFL in vivo is three-dimensional (3D) and asymmetric, unlike in fully developed flow in straight tubes. The three-dimensionality of the CFL as it develops in a vascular network, and the underlying hydrodynamic mechanisms, are not well understood. Using a high-fidelity model of cellular-scale blood flow in microvascular networks with in vivo-like topologies, we present a detailed analysis of the fully 3D and asymmetric nature of the CFL in such networks. We show that the CFL significantly varies over different aspects of the networks. Along the vessel lengths, such variations are predominantly non-monotonic, which indicates that the CFL profiles do not simply become more symmetric over the length as they would in straight vessels. We show that vessel tortuosity causes the CFL to become more asymmetric along the length. We specifically identify a curvature-induced migration of the RBCs as the underlying mechanism of increased asymmetry in curved vessels. The vascular bifurcations and mergers are also seen to change the CFL profiles, and in the majority of them the CFL becomes more asymmetric. For most bifurcations, this is generally observed to occur such that the CFL downstream narrows on the side of the vessel nearest the upstream bifurcation, and widens on the other side. The 3D aspects of such behaviour are elucidated. For many bifurcations, a discrepancy exists between the CFL in the daughter vessels, which arises from a disproportionate partitioning between the flow rate and RBC flux. For most mergers, the downstream CFL narrows in the plane of the merger, but widens away from this plane. The dominant mechanism by which such changes occur is identified as the geometric focusing of the two merging streams. To our knowledge, this work provides the first simulation-based analysis of the 3D CFL structure in complex in vivo-like microvascular networks, including the hydrodynamic origins of the observed behaviour.

Detecting Vascular Bifurcation in IVOCT Images Using Convolutional Neural Networks With Transfer Learning

Optical coherence tomography (OCT) technology enables experts to analyze coronary lesions from high-resolution intravascular images. Studies have shown a relationship between vascular bifurcation and a higher occurrence of wall thickening and lesions in these areas. Some level of automation could benefit experts since the visual analysis of pullback frames is a laborious and time-consuming task. Although convolutional neural networks (CNNs) have shown promising results in classifying medical images, in this paper, we found no studies using CNNs in IVOCT images to classify the vascular bifurcation. In this paper, we evaluated four different CNN architectures in the bifurcation classification task trained with the IVOCT images from nine pullbacks from nine different patients. We used data augmentation to balance the dataset, due to the small number of bifurcation-labeled frames, and also applied transfer learning methods to incorporate the knowledge from a lumen segmentation task into some of the evaluated networks. Our classification outperforms other works in this literature, presenting AUC = 99.72%, obtained by a CNN with transferred knowledge.

Tensor Voting Based Vascular Bifurcation Detection in CT Images of Lung

The accurate detection of vascular bifurcations is not helpful for pulmonary vascular disease diagnosis, but vital in (Computed Tomography) CT image analysis and processing of lung. We propose a tensor voting based method for vascular bifurcation detection in CT image of lung, which a vessel enhancement method is firstly proceeding to initially extract vessel structure, on which we perform ball voting with the pixels.

Selective embolization with magnetized microbeads using magnetic resonance navigation in a controlled-flow liver model.

The purpose of this study was to demonstrate the feasibility of using a custom gradient sequence on an unmodified 3T magnetic resonance imaging (MRI) scanner to perform magnetic resonance navigation (MRN) by investigating the blood flow control method invivo, reproducing the obtained rheology in a phantom mimicking porcine hepatic arterial anatomy, injecting magnetized microbead aggregates through an implantable catheter, and steering the aggregates across arterial bifurcations for selective tumor embolization. In the first phase, arterial hepatic velocity was measured using cine phase-contrast imaging in seven pigs under free-flow conditions and controlled-flow conditions, whereby a balloon catheter is used to occlude arterial flow and saline is injected at different rates. Three of the seven pigs previously underwent selective lobe embolization to simulate a chemoembolization procedure. In the second phase, the measured invivo controlled-flow velocities were approximately reproduced in a Y-shaped vascular bifurcation phantom by injecting saline at an average rate of 0.6mL/s with a pulsatile component. Aggregates of 200-μm magnetized particles were steered toward the right or left hepatic branch using a 20-mT/m MRN gradient. The phantom was oriented at 0°, 45°, and 90° with respect to the B0 magnetic field. The steering differences between left-right gradient and baseline were calculated using Fisher's exact test. A theoretical model of the trajectory of the aggregate within the main phantom branch taking into account gravity, magnetic force, and hydrodynamic drag was also designed, solved, and validated against the experimental results to characterize the physical limitations of the method. At an injection rate of 0.5mL/s, the average flow velocity decreased from 20±15 to 8.4±5.0cm/s after occlusion in nonembolized pigs and from 13.6±2.0 to 5.4±3.0cm/s in previously embolized pigs. The pulsatility index measured to be 1.7±1.8 and 1.1±0.1 for nonembolized and embolized pigs, respectively, decreased to 0.6±0.4 and 0.7±0.3 after occlusion. For MRN performed at each orientation, the left-right distribution of aggregates was 55%, 25%, and 75% on baseline and 100%, 100%, and 100% (P<0.001, P=0.003, P=0.003) after the application of MRN, respectively. According to the theoretical model, the aggregate reaches a stable transverse position located toward the direction of the gradient at a distance equal to 5.8% of the radius away from the centerline within 0.11s, at which point the aggregate will have transited through a longitudinal distance of 1.0mm from its release position. In this study, we showed that the use of a balloon catheter reduces arterial hepatic flow magnitude and variation with the aim to reduce steering failures caused by fast blood flow rates and low magnetic steering forces. A mathematical model confirmed that the reduced flow rate is low enough to maximize steering ratio. After reproducing the flow rate in a vascular bifurcation phantom, we demonstrated the feasibility of MRN after injection of microparticle aggregates through a dedicated injector. This work is an important step leading to MRN-based selective embolization techniques in humans.

Staplers or clips?: A systematic review and meta-analysis of vessel controlling devices for renal pedicle ligation in laparoscopic live donor nephrectomy.

Background:Controlling of the renal vessels is a critical step in live donor nephrectomy (LDN). Currently, mainly 2 devices, Hem-o-Lok clips and staplers, are utilized to control vessels during LDN. Both of them have advantages and disadvantages.Methods:This systematic review and meta-analysis was aimed to compare the safety and the efficacy of the 2 devices and to identify the better one in LDN. A systematic search for related publications in the databases of PubMed, Medline, Embase, the Cochrane Library, and Web of Science through February 2018 was performed. Eight studies were selected and evaluated with the Newcastle-Ottawa Scale (NOS).Results:The meta-analysis result showed that utilization of Hem-o-Lok clips resulted in greater amount of estimated blood loss (mean differences [MD]: 40.10; 95% confidence interval [CI] 4.37–75.84) and longer time of warm ischemia (WIT) (MD: 55.61; 95% CI 36.79–74.43) than using staplers. Residual vascular length of grafts in clip group was longer than that in stapler group (MD: 2.51; 95% CI 0.78–4.24). However, the differences in primary outcomes such as device failure rate, death rate, and severe hemorrhage rate, were not significant between these 2 groups. In addition, utilization of Hem-o-Lok clips costed approximate $400 lower than staplers per patient.Conclusion:This study revealed that Hem-o-Lok clips and staplers have the similar function in LDN renal ligation, regarding the device failure rate, death rate, and severe hemorrhage rate. However, the surgeons would benefit from the clips in terms of the residue length of vessels, these outstanding features provide operation convenience and flexibility, such as right-sided donor nephrectomies, early vascular bifurcation, and rare vascular variation. In addition, the clips have potential economic advantages. In some developing countries, it would reduce the healthcare expenditure.

Validation of parametric mesh generation for subject-specific cerebroarterial trees using modified Hausdorff distance metrics

Accurate subject-specific vascular network reconstruction is a critical task for the hemodynamic analysis of cerebroarterial circulation. Vascular skeletonization and computational mesh generation for large sections of cerebrovascular trees from magnetic resonance angiography (MRA) is an error-prone, operator-dependent, and very time-consuming task. Validation of reconstructed computational models is essential to ascertain their accuracy and precision, which directly relates to the confidence of CFD computations performed on these meshes. The aim of this study is to generate an imaging segmentation pipeline to validate and quantify the spatial accuracy of computational models of subject-specific cerebral arterial trees. We used a recently introduced parametric structured mesh (PSM) generation method to automatically reconstruct six subject-specific cerebral arterial trees containing 1364 vessels and 571 bifurcations. By automatically extracting sampling frames for all vascular segments and bifurcations, we quantify the spatial accuracy of PSM against the original MRA images. Our comprehensive study correlates lumen area, pixel-based statistical analysis, area overlap and centerline accuracy measurements. In addition, we propose a new metric, the pointwise offset surface distance metric (PSD), to quantify the spatial alignment between dimensions of reconstructed arteries and bifurcations with in-vivo data with the ability to quantify the over- and under-approximation of the reconstructed models. Accurate reconstruction of vascular trees can a practical process tool for morphological analysis of large patient data banks, such as medical record files in hospitals, or subject-specific hemodynamic simulations of the cerebral arterial circulation.

Application value of the clearance of No.253 lymph nodes with priority to fascial space and preserving left colic artery in laparoscopic radical proctectomy

To investigate the application value of the clearance of No.253 lymph nodes with priority to fascial space and preserving left colic artery (LCA) in patients undergoing laparoscopic radical proctectomy. From August 2015 to August 2016, 97 consecutive middle-low rectal cancer patients underwent laparoscopic radical proctectomy using the clearance of No.253 lymph nodes with priority to fascial space and preserving LCA at Department of General Surgery, Tangdu Hospital. Among 97 patients, 45 were females , 52 were males, mean age was (64.3±5.5) years and mean BMI was (22.4±1.8) kg/m2. Brief steps of this clearance: traditional medial approach was the commencement of the dissection at the membrane bridge line in front of iliac vascular bifurcation, then entering into the Toldt's space; superior rectal artery served as the top of the tent and the Toldt's space was extended as far as possible; blunt separation was developed caudally (reaching 2 cm below the sacral promontory), cephalad (reaching the lower part of the pancreas), left laterally (reaching Toldt's line), dextrally (reaching abdominal aorta); after giving priority to fascias space, from the root of inferior mesenteric artery, LCA was exposed and No.253 lymph nodes were dissected. This regimen was suitable for the rectal adenocarcinoma patients without distant metastasis. There was no tension in the intestine and mesenteria after anastomosis in all the 97 patients. One patient received LCA ligation during the clearance, because of thinner LCA resulting in bleeding. The other 96 cases completed the clearance and operation successfully. The mean No.253 lymphadenectomy time was 11-27(17.1±5.3) minutes. The mean number of harvested No.253 lymph node was 0-6(4±2). The No.253 lymph nodes of 6 patients were positive. No.253 regional mesentery was complete in 95 patients. The total harvested number of lymph node was 11-26(17.3±5.3). Six patients with positive lymph nodes aged from 68 to 72 years old and all of them underwent TME operation 6-8 weeks after neoadjuvant chemoradiotherapy. The mean operative time was 89-189(125±35) minutes. The mean estimated blood loss was 10.5-38.6(22.4±10.5) ml. The first exhaust time was 3.0-6.0(5.6±2.1) days. The mean time to extracting the drainage tube was 3.0-5.0(4.5±2.5) days. Anastomotic fistula appeared in 1 case and hemorrhage appeared in 1 case, and these 2 cases were cured by conservative treatment. No perioperative death occurred. The mean postoperative hospital stay was 3.0-10.0(3.6±2.6) days. The clearance of No.253 lymph nodes with priority to fascial space and preserving LCA in laparoscopic radical proctectomy is safe and feasible.

Analysis of red blood cell partitioning at bifurcations in simulated microvascular networks

Partitioning of red blood cells (RBCs) at vascular bifurcations has been studied over many decades using in vivo, in vitro, and theoretical models. These studies have shown that RBCs usually do not distribute to the daughter vessels with the same proportion as the blood flow. Such disproportionality occurs, whereby the cell distribution fractions are either higher or lower than the flow fractions and have been referred to as classical partitioning and reverse partitioning, respectively. The current work presents a study of RBC partitioning based on, for the first time, a direct numerical simulation (DNS) of a flowing cell suspension through modeled vascular networks that are comprised of multiple bifurcations and have topological similarity to microvasculature in vivo. The flow of deformable RBCs at physiological hematocrits is considered through the networks, and the 3D dynamics of each individual cell are accurately resolved. The focus is on the detailed analysis of the partitioning, based on the DNS data, as it develops naturally in successive bifurcations, and the underlying mechanisms. We find that while the time-averaged partitioning at a bifurcation manifests in one of two ways, namely, the classical or reverse partitioning, the time-dependent behavior can cycle between these two types. We identify and analyze four different cellular-scale mechanisms underlying the time-dependent partitioning. These mechanisms arise, in general, either due to an asymmetry in the RBC distribution in the feeding vessels caused by the events at an upstream bifurcation or due to a temporary increase in cell concentration near capillary bifurcations. Using the DNS results, we show that a positive skewness in the hematocrit profile in the feeding vessel is associated with the classical partitioning, while a negative skewness is associated with the reverse one. We then present a detailed analysis of the two components of disproportionate partitioning as identified in prior studies, namely, plasma skimming and cell screening. The plasma skimming component is shown to under-predict the disproportionality, leaving the cell screening component to make up for the difference. The crossing of the separation surface by the cells is observed to be a dominant mechanism underlying the cell screening, which is shown to mitigate extreme heterogeneity in RBC distribution across the networks.

Presence of Anterior Communicating Artery Aneurysm Is Associated With Age, Bifurcation Angle, and Vessel Diameter.

The anterior communicating artery (Acom) aneurysm is the most complex in all cerebral aneurysms, and wider vascular bifurcation angles are considered to be associated with aneurysm formation. The objective of this study was to investigate association of the Acom aneurysm formation with patient age and vascular bifurcation morphology. Three-dimensional angiographic data of 665 patients were used in this study, including 160 patients with Acom aneurysms, 66 with non-Acom aneurysms, and 439 control subjects with no aneurysms. The anterior cerebral artery bifurcation angle (Acom/A2 angle), arterial diameters, and Acom aneurysm geometric characters were examined. Women of 50 to 70 years were more vulnerable to Acom aneurysm formation than men. The Acom/A2 bifurcation angle was significantly increased (P<0.0001) with increase of patient age. The size of the Acom aneurysm dome and neck was statistically positively correlated with the diameter of the Acom, A1 and A2 segments (P<0.0001). The Acom/A2 bifurcation angle was significantly (P<0.0001) wider in patients with than without Acom aneurysms, whereas the A1/A2 angle was significantly smaller in patients with than without Acom aneurysms (P<0.0001). The Acom aneurysms at the bifurcation apex mostly deviated toward the smaller angle formed between the parent A1 and branches and toward the daughter artery with a smaller diameter. The Acom aneurysms were located mostly on the dominant anterior cerebral artery. The presence of Acom aneurysm is significantly associated with patient age, wider angles of the anterior cerebral artery bifurcation, and smaller vascular diameter of the anterior communicating complex.

Direct Numerical Simulation of Cellular-Scale Blood Flow in 3D Microvascular Networks

We present, to our knowledge, the first direct numerical simulation of 3D cellular-scale blood flow in physiologically realistic microvascular networks. The vascular networks are designed following in vivo images and data, and are comprised of bifurcating, merging, and winding vessels. Our model resolves the large deformation and dynamics of each individual red blood cell flowing through the networks with high fidelity, while simultaneously retaining the highly complex geometric details of the vascular architecture. To our knowledge, our simulations predict several novel and unexpected phenomena. We show that heterogeneity in hemodynamic quantities, which is a hallmark of microvascular blood flow, appears both in space and time, and that the temporal heterogeneity is more severe than its spatial counterpart. The cells are observed to frequently jam at vascular bifurcations resulting in reductions in hematocrit and flow rate in the daughter and mother vessels. We find that red blood cell jamming at vascular bifurcations results in several orders-of-magnitude increase in hemodynamic resistance, and thus provides an additional mechanism of increased in vivo blood viscosity as compared to that determined in vitro. A striking result from our simulations is negative pressure-flow correlations observed in several vessels, implying a significant deviation from Poiseuille’s law. Furthermore, negative correlations between vascular resistance and hematocrit are observed in various vessels, also defying a major principle of particulate suspension flow. To our knowledge, these novel findings are absent in blood flow in straight tubes, and they underscore the importance of considering realistic physiological geometry and resolved cellular interactions in modeling microvascular hemodynamics.

Apparent sixth sense in theropod evolution: The making of a Cretaceous weathervane.

ObjectiveTwo separate and distinctive skills are necessary to find prey: Detection of its presence and determination of its location. Surface microscopy of the dentary of albertosaurines revealed a previously undescribed sensory modification, as will be described here. While dentary “foramina” were previously thought to contain tactile sensory organs, the potential function of this theropod modification as a unique localizing system is explored in this study.MethodDentary surface perforations were examined by surface epi-illumination microscopy in tyrannosaurine and albertosaurine dinosaurs to characterize their anatomy. Fish lateral lines were examined as potentially comparable structures.ResultIn contrast to the subsurface vascular bifurcation noted in tyrannosaurines (which lack a lateral dentary surface groove), the area subjacent to the apertures in albertosaurine grooves has the appearance of an expanded chamber. That appearance seemed to be indistinguishable from the lateral line of fish.ConclusionDentary groove apertures in certain tyrannosaurid lines (specifically albertosaurines) not only have a unique appearance, but one with significant functional and behavior implications. The appearance of the perforations in the dentary groove of albertosaurines mirrors that previously noted only with specialized neurologic structures accommodating derived sensory functions, as seen in the lateral line of fish. The possibility that this specialized morphology could also represent a unique function in albertosaurine theropods for interacting with the environment or facilitating prey acquisition cannot be ignored. It is suggested that these expanded chambers function in perceiving and aligning the body relative to the direction of wind, perhaps a Cretaceous analogue of the contemporary midwestern weathervane.

Geometries of vasculature bifurcation can affect the level of trophic damage during formation of a brain ischemic lesion.

Ischemic lesion is a common cause of various diseases in humans. Brain tissue is especially sensitive to this type of damage. A common reason for the appearance of an ischemic area is a stop in blood flow in some branch of the vasculature system. Then, a decreasing concentration gradient results in a low mean level of oxygen in surrounding tissues. After that, the biochemical ischemic cascade spreads. In this review, we examine these well-known events from a new angle. It is stressed that there is essential evidence to predict the formation of an ischemic micro-area at the base of vascular bifurcation geometries. Potential applications to improve neuroprotection are also discussed.

Intraoperative multi-exposure speckle imaging of cerebral blood flow

Multiple studies have demonstrated that laser speckle contrast imaging (LSCI) has high potential to be a valuable cerebral blood flow monitoring technique during neurosurgery. However, the quantitative accuracy and sensitivity of LSCI is limited, and highly dependent on the exposure time. An extension to LSCI called multi-exposure speckle imaging (MESI) overcomes these limitations, and was evaluated intraoperatively in patients undergoing brain tumor resection. This clinical study (n = 8) recorded multiple exposure times from the same cortical tissue area spanning 0.5–20 ms, and evaluated images individually as single-exposure LSCI and jointly using the MESI model. This study demonstrated that the MESI estimates provided the broadest flow sensitivity for sampling the flow magnitude in the human brain, closely followed by the shorter exposure times. Conservation of flow analysis on vascular bifurcations was used to validate physiological accuracy, with highly conserved flow estimates (<10%) from both MESI and 1 ms LSCI (n = 14 branches). The MESI model had high goodness-of-fit with proper image calibration and acquisition, and was used to monitor blood flow changes after tissue cautery. Results from this study demonstrate that intraoperative MESI can be performed with high quantitative accuracy and sensitivity for cerebral blood flow monitoring.