Local Vessel Research Articles

Hemodynamic parameters and vessel tortuosity: an investigation with a mesenterial vascular network

Purpose: The effect of hemodynamic parameters on vessel tortuosity remains un-clear. Here we investigate the correlation of tortuosity with a set of hemodynamicparameters in a mesenterial vascular network.Methods: A mesenterial vascular network of 389 vessels (131 arteries, 132 veins, and 126 capillaries) was imaged. Eleven hemodynamic parameters were measured (pressure, wall shear stress, diameter, blood velocity and flow, viscosity, haematocrit, partial oxygen saturation, oxygen saturation, wall thickness, and local vessel density). Tortuosity was assessed quantitatively with a validated algorithm and correlation computed with subsets of hemodynamic parameters selected by a lasso regressor.Results: Results suggest that tortuosity is related to pressure, wall shear stress, diameter, blood velocity, viscosity, partial but not full oxygen saturation, and wall thickness for the arteries; diameter, blood flow, hematocrit, and density for the veins; and viscosity (but not hematocrit), partial and full oxygen saturation, and density for the capillaries. The combination of hemodynamic parameters correlating best with tortuosity is the set of all parameters except density (r = 0.64, p < 0.01), using as tortuosity definition the set of tortuosity features (geometric measures) correlating best with a single hemodynamic factor for the arteries.Conclusion: This pilot suggests two general conclusions. First, the quantitative definition of tortuosity (i.e., the set of geometric features adopted) should be tuned to the specific data and problem considered. Second, tortuosity is caused by a combination of hemodynamic factors, not a single one.

Artificial Zinc-Finger Transcription Factor of A20 Suppresses Restenosis in Sprague Dawley Rats after Carotid Injury via the PPARα Pathway.

The inhibition of inflammation and vascular smooth muscle cell (VSMC) proliferation is an ideal strategy to suppress intimal hyperplasia after percutaneous transluminal angioplasty (PTA). Evidence has indicated that overexpression of A20 suppresses neointima formation, but its low transfection efficiency limits its application. Hence, we upregulated A20 expression via transfection of rAd.ATF (recombinant adenovirus vector of artificial transcription factor) and rAd.A20 in rat carotid arteries after balloon dilatation (in vivo) and isolated VSMCs (in vitro). In vivo, we found that after rAd.ATF and rAd.A20 transfection, A20 expression was markedly increased, whereas proliferating cell nuclear antigen (PCNA) and nuclear factor κB p65 (NF-κBp65) protein levels were significantly decreased, and intimal hyperplasia and secretion of proinflammatory factors were significantly reduced when compared with empty vector and saline control groups. Most importantly, the rAd.ATF-treated group showed more significant inhibition on intimal hyperplasia and expression of PCNA than the rAd.A20-treated group. In vitro, compared with the control group, transfection of rAd.ATF and rAd.A20 significantly increased A20 expression, which upregulated the proliferator-activated receptor (PPAR) level for both mRNA and protein, and reduced migration and proliferation of VSMCs and lipopolysaccharide (LPS)-induced inflammation. Furthermore, the PPARα agonist GW6471 could partially restore the effect of A20 on VSMCs. Our findings indicate that the ATF of A20 inhibits neointimal hyperplasia and, therefore, constitutes a novel potential alternative to prevent restenosis.

BEM-based simulation of lung respiratory deformation for CT-guided biopsy.

Accurate and real-time prediction of the lung and lung tumor deformation during respiration are important considerations when performing a peripheral biopsy procedure. However, most existing work focused on offline whole lung simulation using 4D image data, which is not applicable in real-time image-guided biopsy with limited image resources. In this paper, we propose a patient-specific biomechanical model based on the boundary element method (BEM) computed from CT images to estimate the respiration motion of local target lesion region, vessel tree and lung surface for the real-time biopsy guidance. This approach applies pre-computation of various BEM parameters to facilitate the requirement for real-time lung motion simulation. The resulting boundary condition at end inspiratory phase is obtained using a nonparametric discrete registration with convex optimization, and the simulation of the internal tissue is achieved by applying a tetrahedron-based interpolation method depend on expert-determined feature points on the vessel tree model. A reference needle is tracked to update the simulated lung motion during biopsy guidance. We evaluate the model by applying it for respiratory motion estimations of ten patients. The average symmetric surface distance (ASSD) and the mean target registration error (TRE) are employed to evaluate the proposed model. Results reveal that it is possible to predict the lung motion with ASSD of [Formula: see text]mm and a mean TRE of [Formula: see text]mm at largest over the entire respiratory cycle. In the CT-/electromagnetic-guided biopsy experiment, the whole process was assisted by our BEM model and final puncture errors in two studies were 3.1 and 2.0mm, respectively. The experiment results reveal that both the accuracy of simulation and real-time performance meet the demands of clinical biopsy guidance.

Pericytes impair capillary blood flow and motor function after chronic spinal cord injury.

Blood vessels in the central nervous system (CNS) are controlled by neuronal activity; for example, widespread vessel constriction (vessel tone) is induced by brainstem neurons that release the monoamines serotonin and noradrenaline, and local vessel dilation is induced by glutamatergic neuron activity. Here, we examined how vessel tone adapts to the loss of neuron-derived monoamines after spinal cord injury (SCI) in rats. We find that, months after the imposition of SCI, the spinal cord below the site of injury is in a chronic state of hypoxia, due to paradoxical excess activity of monoamine receptors (5-HT1) on pericytes, despite the absence of monoamines. This monoamine receptor activity causes pericytes to locally constrict capillaries, reducing blood flow to ischemic levels. Receptor activation in the absence of monoamines results from the production of trace amines (such as tryptamine) by pericytes that ectopically express the enzyme aromatic-l-amino-acid-decarboxylase (AADC), which synthesizes trace amines directly from dietary amino acids (such as tryptophan). Inhibition of monoamine receptors or of AADC, or even increased inhaled oxygen, produces substantial relief from hypoxia and improves motoneuron and locomotor function after SCI.

Reproductive cycle of seabob shrimp Xiphopenaeus kroyeri (Crustacea, Penaeidea) from the northeast coast of Brazil

The reproductive cycle of Xiphopenaeus kroyeri north-eastern Brazil was described to contribute to the sustainable management of this stock in the region. Specimens were collected monthly from August 2011 to July 2012 using a local vessel of the artisanal fleet. A total of 1201 individuals were analyzed (673 females and 528 males) with a mean carapace length (CL) of 1.88 ± 0.16 cm and total length (TL) of 9.00 ± 1.22 cm. The lowest CL and TL of mature females were 1.33 and 6.5 cm, respectively, and all females above 2.44 cm (CL) and 11.5 cm (TL) were mature. Ovarian maturation was classified into four stages: I (immature), II (maturing), III (mature) and IV (spawned). Individuals of all maturational stages were present throughout the year. Considering the macro and microscopic analysis, it was suggested that this species in north-eastern Brazil has a continuous reproductive cycle, with two seasonal peaks, November/December and February (austral spring and summer). A positive correlation between the percentage of mature females and temperature was observed, and a higher percentage was reported in the warmer months of the year. This suggests that the reproductive peaks can be triggered by water temperature variation throughout the year.

Identifying Key Domains in Endothelial IQGAP1 Critical for Leukocyte Transmigration

Inflammation results in the dilation of local blood vessels, the activation of endothelium by cytokines and the recruitment of circulating leukocytes into areas of tissue damage. The majority of leukocytes undergo transendothelial migration (TEM) by using a unique endothelial cell membrane system referred to as the lateral border recycling compartment (LBRC). IQ‐domain GTPase‐activating protein 1 (IQGAP1) was identified as an LBRC‐associated protein and subsequently found to be essential for TEM. IQGAP1 is a scaffolding protein comprised of six major interaction domains. It has been reported to interact productively with over 135 cellular proteins. In endothelial cells IQGAP1 partially localizes to cell borders and knocking down its expression prevents TEM. However, it is not known which of the many proteins it is known to interact with carries out its role in TEM. Since these proteins bind to specific IQGAP1 domains, as a first step toward understanding the mechanism by which IQGAP1 regulates TEM, we explored which of its six protein interactions domains were critical for its function. We knocked down IQGAP1 in endothelial cells and re‐expressed truncated forms of IQGAP1 with specific regions deleted to identify the regions (and thereby the potential binding partners) that are critical for TEM. We show that the actin‐binding domain and the calmodulin‐binding isoleucine‐glutamine (IQ) domain of IQGAP1 are critical for its function during TEM.Human endothelial cells in which >80% of endogenous IQGAP1 was depleted by shRNA did not support TEM; re‐expression of wild‐type IQGAP1 restored TEM to control levels. Re‐expression of IQGAP1 with a GFP‐tagged construct after knockdown also showed IQGAP1 enrichment around transmigrating leukocytes. Re‐expression of IQGAP1 truncation mutants lacking the N‐terminal actin‐binding domain did not localize to endothelial borders and did not support TEM. Re‐expression of truncated IQGAP1 constructs containing the actin‐binding domain and the IQ domain localized to cell borders and supported TEM. Constructs containing the actin‐binding domain but lacking the IQ domain localized to the cell borders but did not restore TEM.After identifying the IQ domain as having a critical role in TEM, we generated specific point mutations in this domain within the full‐length construct. In particular, the isoleucine (I)‐glutamine (Q) motif after which the IQ domain is named has been identified in the literature as having an essential role in IQGAP1 function and we are currently testing whether they are also important in TEM. Using these constructs in future studies will help identify the role of the IQ domain in TEM and its interacting partner(s). Identifying the binding partners of IQGAP1 that are critical for inflammation will provide clues to its mechanism of action and potential therapeutic targets for anti‐inflammatory therapy.Support or Funding InformationFunded by R01 HL046849, R01 HL064774, Alpha Omega Alpha Carolyn Kuckein Student Research Fellowship

Abstract A19: Lymphatic vessels as a biomarker in human melanoma

Abstract The aim of our work is to assess the local lymphatic vasculature within the tumor microenvironment as a possible biomarker for response to immunotherapy. Targeting the immune checkpoint molecules CTLA-4 and PD-1 is showing unprecedented clinical impact in human melanoma patients. However, a significant subset of patients does not respond to therapy. Therefore efforts have been made to identify biomarkers predictive of survival and response to immunotherapy, and evaluation of the immune microenvironment was shown to have high prognostic power. Characterization of tumor-infiltrating T cells with respect to density, phenotype and location has been demonstrated to predict survival and metastasis in retrospective studies and might be superior to classical TNM staging. Despite these promising results current strategies are not 100% predictive and additional cell populations within the tumor microenvironment are likely to affect the overall anti-tumor immune response. Interestingly, the density of tumor-associated lymphatic vessels was found to be decreased in patients with metastatic colorectal cancer compared to non-metastatic patients. In addition, our recent work using metastatic melanoma samples from the Broad Institute's TCGA database demonstrated that expression of lymphatic genes (LYVE-1 and podoplanin) correlates with expression levels of immune cell markers. In mice lacking dermal lymphatic vessels immune infiltration into experimental melanoma was significantly decreased. At the same time these tumors displayed decreased immune suppression and improved tumor control by transferred cytotoxic T cells. These results suggest that lymphatic vessels are essential for establishment of an efficient anti-tumor immune response, but have a role in negatively regulating anti-tumor immunity during tumor progression. We therefore hypothesize that local lymphatic vessel density within the tumor microenvironment predicts immune infiltrate and response to immunotherapy. To simultaneously evaluate immune and vascular components in human formalin-fixed samples of melanoma we are using a multiplex-immunohistochemistry-based approach, which allows for examination of up to twelve markers by sequential staining of a single marker at a time. Tissue regions that include tumor/stroma borders and show high CD8+ T cell infiltrates are selected for analysis. This is followed by tissue segmentation based on the presence of a tumor marker and automated detection of cell populations within intra-tumoral regions and the invasive margin at the tumor border. Analysis using image cytometry allows us to quantify and correlate presence and location of multiple cell types within the tumor and the surrounding stroma. Our work will contribute to improved stratification of cancer patients with respect to possible response to immunotherapy. Citation Format: Julia Femel, Takahiro Tsujikawa, Guillaume Thibault, Jamie Booth, Amanda W. Lund. Lymphatic vessels as a biomarker in human melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A19.

Classification of mechanisms of strut malapposition after angiographically optimized stent implantation: An optical coherence tomography study.

To elucidate causes and extent of strut malapposition in angiographically optimized stenting. Using a new classification system for strut malapposition, the mechanisms of stent strut malapposition were classified as localized lumen enlargement, vessel asymmetry, stent undersizing, strut underexpansion and stent deployment issue. Stent implantations (n = 110) in 100 consecutive patients undergoing optical coherence tomography (OCT) after the operator considered the stent as optimally deployed angiographically were reviewed to determine if strut apposition was complete. 127,894 stent struts in 110 stents were analyzed. There were 6,644 struts malapposed (5.2% ±7.3%), with strut malapposition found in 82 of 110 stents (74.5%). Localized lumen enlargement was the most common cause of malapposition (74.4% of malapposition clusters). Stent undersizing was the second most common cause (46.3%) followed by strut under-expansion in 29.3%, stent deployment issue in 18.2%, and vessel asymmetry in 9.7%. Malapposition of any degree is common after angiographic stent optimization, occurring in up to three-quarters of stents. The most frequent mechanism was localized lumen enlargement. The second most common cause of strut malapposition was stent undersizing, which was angiographically invisible. Whether performing OCT after angiographic optimization improves short- and long-term outcomes requires further study. © 2017 Wiley Periodicals, Inc.

Robust and accurate optic disk localization using vessel symmetry line measure in fundus images

Accurate optic disk (OD) localization is an important step in fundus image based computer-aided diagnosis of glaucoma and diabetic retinopathy. Robust OD localization becomes more challenging with the presence of common pathological variations which could alter its overall appearance. This paper presents a novel OD localization method by incorporating salient visual cues of retinal vasculature: (1) global vessel symmetry, (2) vessel component count and (3) local vessel symmetry inside OD region. In the proposed method, a new vessel symmetry line (VSL) measure is designed to demarcate the lines that divide the retinal vasculature into approximately similar halves. The initial OD center location is computed using the highest number of major blood vessel components in the skeleton image. The final OD center localization involves an iterative center of mass computation to exploit the local vessel symmetry in the OD region of interest. The proposed method shows effectiveness in diseased retinas having diverse symptoms like bright lesions, hemorrhages, and tortuous vessels that create potential ambiguity for OD localization. A total of ten publicly available retinal image databases are considered for extensive evaluation of the proposed method. The experimental results demonstrate high average OD detection accuracy of 99.49%, while achieving state-of-the-art OD localization error in all databases.

Retinal Image Denoising via Bilateral Filter with a Spatial Kernel of Optimally Oriented Line Spread Function

Filtering belongs to the most fundamental operations of retinal image processing and for which the value of the filtered image at a given location is a function of the values in a local window centered at this location. However, preserving thin retinal vessels during the filtering process is challenging due to vessels' small area and weak contrast compared to background, caused by the limited resolution of imaging and less blood flow in the vessel. In this paper, we present a novel retinal image denoising approach which is able to preserve the details of retinal vessels while effectively eliminating image noise. Specifically, our approach is carried out by determining an optimal spatial kernel for the bilateral filter, which is represented by a line spread function with an orientation and scale adjusted adaptively to the local vessel structure. Moreover, this approach can also be served as a preprocessing tool for improving the accuracy of the vessel detection technique. Experimental results show the superiority of our approach over state-of-the-art image denoising techniques such as the bilateral filter.

Simulating Heterogeneous Tumor Cell Populations.

Certain tumor phenomena, like metabolic heterogeneity and local stable regions of chronic hypoxia, signify a tumor’s resistance to therapy. Although recent research has shed light on the intracellular mechanisms of cancer metabolic reprogramming, little is known about how tumors become metabolically heterogeneous or chronically hypoxic, namely the initial conditions and spatiotemporal dynamics that drive these cell population conditions. To study these aspects, we developed a minimal, spatially-resolved simulation framework for modeling tissue-scale mixed populations of cells based on diffusible particles the cells consume and release, the concentrations of which determine their behavior in arbitrarily complex ways, and on stochastic reproduction. We simulate cell populations that self-sort to facilitate metabolic symbiosis, that grow according to tumor-stroma signaling patterns, and that give rise to stable local regions of chronic hypoxia near blood vessels. We raise two novel questions in the context of these results: (1) How will two metabolically symbiotic cell subpopulations self-sort in the presence of glucose, oxygen, and lactate gradients? We observe a robust pattern of alternating striations. (2) What is the proper time scale to observe stable local regions of chronic hypoxia? We observe the stability is a function of the balance of three factors related to O2—diffusion rate, local vessel release rate, and viable and hypoxic tumor cell consumption rate. We anticipate our simulation framework will help researchers design better experiments and generate novel hypotheses to better understand dynamic, emergent whole-tumor behavior.

Simultaneous mapping of unevenly distributed tissue hypoxia and vessel permeability in tumor microenvironment

New blood vessels that form within tumors undergo repeated irregular divergence, joining, and twisting, resulting in blood vessels with abnormal tissue distribution, structure, and function. Tumor vessels exhibit increased spatially uneven permeability and oxygen delivery, characteristics that may reduce the efficacy of radiotherapy and chemotherapy. Therefore, it is vital to establish technologies for quantitatively mapping hypoxia and vessel permeability within tumors to clarify tumor mechanisms. However, existing methods can only acquire mean measurements within a given region or the entire tissue, and there have been no reports of technologies for measuring permeability at multiple points in individual vessels or for simultaneously performing oxygen partial pressure mapping. Here, new blood vessels formed within tumors were detected on fluorescent blood flow images, and measurement points were set at fixed intervals across individual blood vessels. Fluorescent dye that leaked out over time was excited with a continuous wave optical laser to calculate the permeability distribution of individual vessels. On the other hand, an oxygen probe dye was excited with a pulse laser and oxygen concentration-dependent light emission was analyzed to map oxygen partial pressure. Oxygen partial pressure imaging in tumors transplanted onto the backs of mice showed that tissue regions surrounding minute tumor vessels were generally hypoxic. Furthermore, compared with the normal dermal vasculature, there was greater variation in vessel permeability, and sites with very high vessel permeability were detected. We designed a system for high-resolution spatial mapping of blood vessel permeability and tissue oxygenation in tumor microvasculatures, thereby clarifying the relationship between local hypoxia and vessel permeability. It is anticipated that these findings could be applied to improve anticancer drug delivery and radiotherapy by identifying the dependence of local tissue oxygenation on the vessel structure and hemodynamics.

The Arteriovenous (AV) Loop in a Small Animal Model to Study Angiogenesis and Vascularized Tissue Engineering.

A functional blood vessel network is a prerequisite for the survival and growth of almost all tissues and organs in the human body. Moreover, in pathological situations such as cancer, vascularization plays a leading role in disease progression. Consequently, there is a strong need for a standardized and well-characterized in vivo model in order to elucidate the mechanisms of neovascularization and develop different vascularization approaches for tissue engineering and regenerative medicine. We describe a microsurgical approach for a small animal model for induction of a vascular axis consisting of a vein and artery that are anastomosed to an arteriovenous (AV) loop. The AV loop is transferred to an enclosed implantation chamber to create an isolated microenvironment in vivo, which is connected to the living organism only by means of the vascular axis. Using 3D imaging (MRI, micro-CT) and immunohistology, the growing vasculature can be visualized over time. By implanting different cells, growth factors and matrices, their function in blood vessel network formation can be analyzed without any disturbing influences from the surroundings in a well controllable environment. In addition to angiogenesis and antiangiogenesis studies, the AV loop model is also perfectly suited for engineering vascularized tissues. After a certain prevascularization time, the generated tissues can be transplanted into the defect site and microsurgically connected to the local vessels, thereby ensuring immediate blood supply and integration of the engineered tissue. By varying the matrices, cells, growth factors and chamber architecture, it is possible to generate various tissues, which can then be tailored to the individual patient's needs.

Approaching Tumor Tissue in Local Blood Vessel for Targeted Drug Delivery by Nanorobots

This paper describes a nanorobot control algorithm designed for approaching tumor tissue in local blood vessel for targeted drug delivery. The algorithm coordinates nanorobots’ movements through use of two types of chemical molecules, an acoustic signal and velocity characteristic of blood fluid. After detecting the chemical molecules released by cancer cells, a nanorobot moves toward the area of higher concentration of the molecule and releases another chemical molecule which alerts others to aggregate to the target. When nanorobots detect acoustic signals emitted by nanorobots reaching target, their paths will be planned according to intensity of acoustic signals and velocity characteristic of blood fluid. The simulations show that compared with the existed approaches, the proposed algorithm results in an increase of nanorobots’ population and a decrease of cost time to reach target site with the help of acoustic signals and velocity characteristic. As a whole, the results obtained suggest that the algorithm presented in this paper is a better strategy for approaching tumor tissue in local blood vessel by nanorobots.

Novel Uses for Botulinum Neurotoxin in Upper Limb Surgery.

Novel Uses for Botulinum Neurotoxin in Upper Limb Surgery.

Cathodic-controlled and near-infrared organic upconverter for local blood vessels mapping.

Organic materials are used in novel optoelectronic devices because of the ease and high compatibility of their fabrication processes. Here, we demonstrate a low-driving-voltage cathodic-controlled organic upconverter with a mapping application that converts near-infrared images to produce images of visible blood vessels. The proposed upconverter has a multilayer structure consisting of a photosensitive charge-generation layer (CGL) and a phosphorescent organic light-emitting diode (OLED) for producing clear images with a high resolution of 600 dots per inch. In this study, temperature-dependent electrical characterization was performed to analyze the interfacial modification of the cathodic-controlled upconverter. The result shows that the upconverter demonstrated a high conversion efficiency of 3.46% because of reduction in the injection barrier height at the interface between the CGL and the OLED.

Lymphatic vessels regulate immune microenvironments in human and murine melanoma.

Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment.

Optic Disc Localization Using Directional Models.

Reliable localization of the optic disc (OD) is important for retinal image analysis and ophthalmic pathology screening. This paper presents a novel method to automatically localize ODs in retinal fundus images based on directional models. According to the characteristics of retina vessel networks, such as their origin at the OD and parabolic shape of the main vessels, a global directional model, named the relaxed biparabola directional model, is first built. In this model, the main vessels are modeled by using two parabolas with a shared vertex and different parameters. Then, a local directional model, named the disc directional model, is built to characterize the local vessel convergence in the OD as well as the shape and the brightness of the OD. Finally, the global and the local directional models are integrated to form a hybrid directional model, which can exploit the advantages of the global and local models for highly accurate OD localization. The proposed method is evaluated on nine publicly available databases, and achieves an accuracy of 100% for each database, which demonstrates the effectiveness of the proposed OD localization method.

Neointimal coverage on acute vessel wall injuries after stenting: 6-month follow-up study.

Stent implantation often creates local vessel wall injuries which can be characterized in detail by optical coherence tomography (OCT). Little is known about the neointimal coverage at these areas. We aimed to evaluate neointimal coverage of vessel wall injuries area associated with stent implantation. We retrospectively selected patients implanted with sirolimus-eluting stents (SES) having excellent OCT images immediately after stent implantation and at the 6-month follow-up. All OCT cross-sectional images were divided into three groups: intra-stent tissue prolapse (ISTP) areas, intra-stent dissection flaps (ISDF) areas, and non-injuried areas. The neointimal coverage in included sections was evaluated at 6 months follow-up. Finally, 1690 cross-sectional images in 74 stents were analyzed totally. Among which, 240 images (14.20%) involved ISTP areas, 124 images (7.34%) at ISDF areas, and 1326 images (78.46%) at non-injuried areas. All ISTP and ISDF were disappeared at six months follow-up, Neointimal thickness at ISTP and ISDF areas increased significantly compared to the one in non-injuried areas (97.4±40.3μm vs. 68.4±47.6μm, P<0.001; 92.7±49.8μm vs. 68.4±47.6μm, P<0.001). Mean neointimal area of ISTP and ISDF areas was almost the same (0.8±0.3 mm2), which both had a significant difference compared to mean neointimal area (0.6±0.4mm2) at non-injuried areas (p1<0.001, p2=0.006). Intra-stent tissue prolapse and intra-stent dissection flaps have benign clinical course up to 6 months. The areas with these local complications, however, have greater neointimal hyperplasia compared to the non-injuried areas.

Atherosclerosis in the circle of Willis: Spatial differences in composition and in distribution of plaques

Background and aimsIntracranial atherosclerosis is one of the main causes of ischemic stroke. However, the characteristics of intracranial arteries and atherosclerosis have rarely been studied. Therefore, we systematically investigated atherosclerotic changes in all arteries of the Circle of Willis (CoW). MethodsSixty-seven CoWs obtained at autopsy from randomly chosen hospital patients (mean age, 67.3 ± 12.5 years), of which a total of 1220 segments were collected from 22 sites. Atherosclerotic plaques were classified according to the revised American Heart Association classification and were related to local vessel characteristics, such as the presence of an external and internal elastic lamina and the elastic fibre density of the media. Results181 out of the 1220 segments had advanced plaques (15%), which were mainly observed in large arteries such as the internal carotid, middle cerebral, basilar and vertebral artery. Only 11 out of 1220 segments (1%) showed complicated plaques (p < 0.001). Six of these were intraplaque hemorrhages (IPH) and observed only in patients who had cardiovascular-related events (p = 0.015). The frequency of characteristics such as the external elastic lamina and a high elastin fibre density in the media was most often associated with the vertebral artery. Only 3% (n = 33) of the CoW arteries contained calcification (p < 0.001), which were mostly observed in the vertebral artery (n = 13, 12%). ConclusionsAdvanced atherosclerotic plaques in the CoW are relatively scarce and mainly located in the 4 large arteries, and mostly characterized by an early and stable phenotype, a low calcific burden, and a low frequency of IPH.