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PURPOSE: This review aimed to evaluate the significance of assessing radial peripheral capillary (RPC) network parameters by optical coherence tomography angiography (OCTA) in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confirmed by polymerase chain reaction. METHODS: A literature search was conducted in the PubMed database to select high-quality reviews and original articles on the use of OCTA for visualizing the RPC network and calculating RPC parameters. RESULTS: The study revealed that systemic hypoxia, hypercoagulable state, and inflammation affect the RPC network in patients with coronavirus disease 2019 (COVID-19). Reduced RPC parameters were observed early in the course of SARS-CoV-2 infection and after several months of follow-up. Additionally, there was a correlation between reduced RPC parameters and subsequent thinning of the retinal nerve fiber layer. CONCLUSIONS: The OCTA examination of the retina and optic disc should be considered in patients with a history of COVID-19 to assess the impact of systemic hypoxia and inflammation on ocular function. Follow-up assessment of these patients is also necessary to understand the potential consequences of ischemia affecting the optic nerve, retina, and choroid.

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OBJECTIVE: To evaluate longitudinal changes in peripapillary vessel density (VD) following coronavirus disease 2019 (COVID-19) using optical coherence tomography angiography. METHODS: As part of a prospective longitudinal observational study, we studied healthy individuals with a history of mild COVID-19 confirmed via real-time polymerase chain reaction. After recovery, we used the Optovue RTVue XR Avanti machine to perform optic nerve head (ONH) imaging. We also assessed the VD of all vessels and of small vessels in the disc and the radial peripapillary capillary (RPC) network at 1 and 3 months post-recovery. RESULTS: We included 17 patients (34 eyes; mean age: 36.9 ± 10.2 years, range: 24-62 years) who had recovered from COVID-19. No changes were observed in the ONH parameters. However, there was a noticeable trend of increased small vessel VD values in the RPC. These increases were significant for the peripapillary whole, superior hemifield, inferior-temporal, temporal-superior, and superior-temporal small vessels. Moreover, the evaluation of all vessel VD values in the RPC revealed a significant decrease in the inside disc and a significant increase in a grid-based inferior region. CONCLUSION: COVID-19 may affect VD of the RPC in the ONH, and should be considered in ONH evaluations.

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Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.

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Background and objectives: We aimed to investigate changes in the radial peripapillary capillary (RPC) network using optical coherence tomography angiography (OCTA) in patients who recovered from coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study of patients hospitalized due to COVID-19 bilateral pneumonia between March and May 2021. The control group included healthy individuals matched for age and sex. Two months after discharge, the patients underwent ophthalmological examination, including optical coherence tomography (OCT) imaging. The RPC network and retinal nerve fiber layer (RNFL) of the optic disc (RNFL optic disc) were automatically evaluated and compared between the study groups. Additionally, the RPC parameters were compared between the men and women in the COVID-19 group, and correlations between the RPC and RNFL optic disc parameters were assessed. Results: A total of 63 patients (120 eyes) with bilateral pneumonia caused by severe acute respiratory syndrome coronavirus 2 infection were examined. No ophthalmic symptoms were reported by the patients. No significant differences were observed in the RPC parameters between the patients from the COVID-19 group and the 43 healthy controls. Moreover, the RPC parameters did not differ between the men and women in the COVID-19 group. A positive correlation was found between the RPC and RNFL optic disc parameters in the COVID-19 patients (p < 0.001). Conclusions: No changes in the RPC network were observed among the patients with COVID-19 bilateral pneumonia in the early period after hospital discharge. However, a longer follow-up is needed to monitor COVID-19-related changes in the microvasculature of the optic nerve head.

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High blood pressure (BP) is a common disease and is associated with many chronic diseases. Measuring BP is essential for the treatment and management of many diseases, and therefore there is a growing need for a non-invasive, sleeveless and continuous BP monitoring device. With the development of technology, pulse waveform analysis using photoplethysmography (PPG) has become more feasible for evaluating BP. This study aimed to evaluate the changes of vascular elasticity and blood volume over time by using the characteristic parameters extracted by PPG. We reviewed the latest progress and literature on the observation of capillary network characteristics in hypertensive and non-hypertensive patients by PPG, the influence of different drugs on microcirculation characteristics in hypertensive patients with PPG, and further explored the key relationship between microcirculation and hypertension. We found that the PPG waveform produced by the fingertips of hypertensive patients is very different from that of healthy people, and the PPG waveform changes significantly during diastolic period after antihypertensive treatment. With the rapid development of medical technology, people can get more intuitive microcirculation image data, which provides beneficial help for the comprehensive understanding of hypertension.

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Idiopathic macular telangiectasia refers to a disease entity characterized by telangiectasia and alteration of the juxtafoveal capillary network. It can present uniocularly or binocularly and is subdivided into three groups which have varied appearances. Group I occurs in males which is easily identifiable and has macular edema. Group II has no sex predilection and difficult to distinguish by clinical examination and often requires the need of optical coherence tomography and angiographic modalities. Group III is not so common with its progressive nature and associated with neurological diseases. This article is aimed to provide complete details about idiopathic macular telangiectasia/idiopathic juxtafoveal telangiectasia/parafoveal telangiectasia including various groups, pathology, presentation, and management.

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The blood-brain barrier (BBB) is a type of capillary network characterized by a highly selective barrier, which restricts the transport of substances between the blood and nervous system. Numerous in vitro models of the BBB have been developed for drug testing, but a BBB model with controllable capillary structures remains a major challenge. In this study, we report for the first time a unique method of controlling the blood capillary networks and characteristic holes formation in a BBB model by varying the elastic modulus of a three-dimensional scaffold. The characteristic hole structures are formed by the migration of endothelial cells from the model surface to the interior, which have functions of connecting the model interior to the external environment. The hole depth increased, as the elastic modulus of the fibrin gel scaffold increased, and the internal capillary network length increased with decreasing elastic modulus. Besides, internal astrocytes and pericytes were also found to be important for inducing hole formation from the model surface. Furthermore, RNA sequencing indicated up-regulated genes related to matrix metalloproteinases and angiogenesis, suggesting a relationship between enzymatic degradation of the scaffolds and hole formation. The findings of this study introduce a new method of fabricating complex BBB models for drug assessment.

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This study investigated the partitioning characteristics of red blood cells (RBCs) within capillaries, with a specific focus on ladder structures observed near the end of the capillaries. In vitro experiments were conducted using microfluidic channels with a ladder structure model comprising six bifurcating channels that exhibited an anti-parallel flow configuration. The effects of various factors, such as the parent channel width, distance between branches, and hematocrit, on RBC partitioning in bifurcating channels were evaluated. A decrease in the parent channel width resulted in an increase in the heterogeneity in the hematocrit distribution and a bias in the fractional RBC flux. Additionally, variations in the distance between branches affected the RBC distribution, with smaller distances resulting in greater heterogeneity. The bias of the RBC distribution in the microchannel cross section had a major effect on the RBC partitioning characteristics. The influence of hematocrit variations on the RBC distribution was also investigated, with lower hematocrit values leading to a more pronounced bias in the RBC distribution. Overall, this study provides valuable insights into RBC distribution characteristics in capillary networks, contributing to our understanding of the physiological mechanisms of RBC phase separation in the microcirculatory system. These findings have implications for predicting oxygen heterogeneity in tissues and could aid in the study of diseases associated with impaired microcirculation.

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Introduction: We present a novel semi-automated computerized method for the detection and quantification of parafoveal capillary network (PCN) in fluorescein angiography (FA) images. Material and Methods: An algorithm detecting the superficial parafoveal capillary bed in high-resolution grayscale FA images and creating a one-pixel-wide PCN skeleton was developed using MatLab software. In addition to PCN detection, capillary density and branch point density in two circular areas centered on the center of the foveal avascular zone of 500µm and 750µm radius was calculated by the algorithm. Three consecutive FA images with distinguishable PCN from 56 eyes from 56 subjects were used for analysis. Both manual and semi-automated detection of the PCN and branch points was performed and compared. Three different intensity thresholds were used for the PCN detection to optimize the method defined as mean(I)+0.05*SD(I), mean(I) and mean(I)-0.05*SD(I), where I is the grayscale intensity of each image and SD the standard deviation. Limits of agreement (LoA), intraclass correlation coefficient (ICC) and Pearson's correlation coefficient (r) were calculated. Results: Using mean(I)-0.05*SD(I) as threshold the average difference in PCN density between semi-automated and manual method was 0.197 (0.316) deg-1 at 500µm radius and 0.409 (0.562) deg-1 at 750µm radius. The LoA were -0.421 to 0.817 and -0.693 to 1.510 deg-1, respectively. The average difference of branch point density between semi-automated and manual method was zero for both areas; LoA were -0.001 to 0.002 and -0.001 to 0.001 branch points/degrees2, respectively. The other two intensity thresholds provided wider LoA for both metrics. The semi-automated algorithm showed great repeatability (ICC>0.91 in the 500µm radius and ICC>0.84 in the 750µm radius) for both metrics. Conclusion: This semi-automated algorithm seems to provide readings in agreement with those of manual capillary tracing in FA. Larger prospective studies are needed to confirm the utility of the algorithm in clinical practice.

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Bronchopulmonary dysplasia (BPD) is a developmental disorder of infants born prematurely, characterized by disrupted alveolarization and microvascular maturation. However, the sequence of alveolar and vascular alterations is currently not fully understood. Therefore, we used a rabbit model to evaluate alveolar and vascular development under preterm birth and hyperoxia, respectively. Pups were born by cesarean section 3 days before term and exposed for 7 days to hyperoxia (95% O2) or normoxia (21% O2). In addition, term-born rabbits were exposed to normoxia for 4 days. Rabbit lungs were fixed by vascular perfusion and prepared for stereological analysis. Normoxic preterm rabbits had a significantly lower number of alveoli than term rabbits. The number of septal capillaries was lower in preterm rabbits but less pronounced than the alveolar reduction. In hyperoxic preterm rabbits, the number of alveoli was similar to that in normoxic preterm animals; however, hyperoxia had a severe additional negative effect on the capillary number. In conclusion, preterm birth had a strong effect on alveolar development, and hyperoxia had a more pronounced effect on capillary development. The data provide a complex picture of the vascular hypothesis of BPD which rather seems to reflect the ambient oxygen concentration than the effect of premature birth.

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PURPOSE: This study evaluates the diagnostic capabilities and the prognostic value of nailfold capillaroscopy data of patients with diabetic retinopathy (DR) to develop an algorithm of monitoring patients with type 2 diabetes mellitus. MATERIAL AND METHODS: The study involved 90 patients (mean age 67 years), among them 31 with nonproliferative diabetic retinopathy, 29 patients with proliferative DR and 30 patients without retinopathy. In addition to conventional ophthalmological examination, optical coherence tomography angiography (OCTA) on the Optovue RTVue-100 device (USA) was performed using en face vessel density protocol to examine the state of the microvasculature of the superficial and deep layers of the vascular plexus of the central retinal zone, as well as nailfold capillaroscopy using computerized capillaroscope KK-01 (ZAO Centr Analiz veshhestv, Russia). RESULTS: The cut-off points for detecting the presence of non-proliferative DR (capillary network density below 38.4%, arterial velocity below 512 mm/s and venous blood flow below 585 mm/s), and the presence of proliferative DR (capillary network density below 30.4%, the arterial velocity below 451 mm/s and the venous blood flow below 441 mm/s) were identified according to ROC-analysis of nailfold capillaroscopy data. In the diagnosis of proliferative DR the capillary network density parameter has a slightly higher diagnostic information value (AUC=0.963) than arterial blood flow velocity (AUC=0.941) or venous blood flow velocity (AUC=0.909). Using the identified critical parameters for predicting the initial and proliferative DR, we created a diagnostic algorithm involving a comprehensive assessment of all characteristics. CONCLUSION: The study revealed that nailfold capillaroscopy indicators (capillary network density, velocity of arterial and venous blood flow) have high diagnostic information value for detecting both non-proliferative and proliferative retinopathy. We constructed mathematical models for predicting DR with an accuracy of predicting the presence of a non-proliferative stage in 92.2% of cases and a proliferative stage in 94.4% of cases. For practical use in clinical environment, we created a computer program calculating the results of DR predictions according to nailfold capillaroscopy data.

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Peripapillary capillary network using optical coherence tomography angiography (OCT-A) was analysed in two siblings suffering from dominant optic atrophy linked to OPA-1 gene mutation. Peripapillary capillary network has been scarcely described in this type of optic atrophy.

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In the crown pulp of brachydont teeth, a cell-free and a cell-rich zone are established beneath the odontoblastic layer, indicating a mature status. For the equine dental pulp, there are no descriptions which allow for a comparative analysis with regard to functional requirements in terms of lifelong secondary dentin production to compensate for occlusal wear. For histomorphological and immunohistological investigations, ten incisors and ten check teeth were used from seven adult horses and five foals. In the periphery of the equine dental pulp, a constant predentin and odontoblastic cell layer was present, followed by densely packed fibroblastic cells, capillary networks, and a high concentration of nerve fibers, suggesting a subodontoblastic supportive zone. Whilst the size of the equine dental pulp decreased with age, the numbers of blood vessels, nerve fibers, and fibroblastic cells increased with age. Histological analysis of the equine dental pulp did not show a cell-free and cell-rich zone as described in the brachydont crown pulp. The equine dental pulp remained in a juvenile status even in aged horses, with morphological features indicating a high capacity for dentine production.

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BACKGROUND: To evaluate changes in the vessel density (VD) of the optic nerve head (ONH) microvasculature in thyroid eye disease (TED) using optical coherence tomography angiography (OCTA). This study aimed to applicate the OCTA as a noninvasive modality in screening TED patients to assess sub-clinical changes. METHODS: In a cross-sectional study, the control group patients were healthy individuals with no ocular abnormalities and were euthyroid. All patients with TED had clinical features of the disease. We divided them into two groups using the clinical activity score (CAS). Patients with CAS scores 0-2 were categorized as group A, and scores three or more as group B. All vessels (AV) and small vessels (SV) VD inside disc and radial peripapillary capillary network were measured using the ONH-OCTA. RESULTS: We evaluated 29 patients with TED and 28 healthy controls. The mean whole image AV VD (mean ± SD: 56.33 ± 2.56, p-value = 0.17) and the mean whole image SV VD (mean ± SD: 49.94 ± 2.56, p-value = 0.16) in the TED group had no statically significant difference compared with the control group (AV mean ± SD: 57.20 ± 20.22, SV mean ± SD: 50.84 ± 2.23). We found a non-significant decrease in AV and SV radial peripapillary capillary VD in the TED group. There was a significant decrease in the mean whole image AV VD (mean ± SD: 54.83 ± 3.07, p-value = 0.005) and the mean whole image SV VD (mean ± SD: 48.60 ± 3.18, p-value = 0.013) in CAS group B compared to group A (AV mean ± SD: 57.45 ± 1.33, SV mean ± SD: 50.95 ± 1.37). CONCLUSION: Our study showed non-significant ONH vascular alterations in patients with TED, including reduced VD of ONH in the radial peripapillary capillary. Patients with higher CAS scores had a more noticeable decrease in ONH microvasculature.

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PURPOSE: To present the optical coherence tomography angiography (OCT-A) findings of the radial peripapillary capillary (RPC) network in an individual with severe bilateral methanol-induced toxic optic neuropathy (MTON) in comparison to a normal subject and a patient with retinitis pigmentosa. CASE REPORT: A 35-year-old man with severe bilateral MTON was referred to the neuro-ophthalmology clinic at the Labbafinejad Medical Center. The Angio Vue OCT 3D set of 4.5 × 4.5 mm was used to measure the disc and peripapillary vessel density. Two subjects were examined with the same protocol as controls to determine the effect on the RPC vessel density in multiple scenarios. One of the controls was a healthy individual with the prerequisite matches of age and sex while the second one was a known retinitis pigmentosa (RP) patient. RPC density was measured as 37.7 in the patient with MTON, 46.9 in the RP patient, and 54.7 in the healthy control. CONCLUSION: The reduction in the RPC vessel density in a patient with MTON compared to that of a healthy individual and also a patient with RP may be due to the loss of capillaries secondary to the loss of nerve fibers and ganglion cells. Moreover, MTON can be considered an optic neuropathy with direct mitochondrial damage to the endothelial cells of the capillaries.

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To investigate the partitioning properties of red blood cells (RBCs) in the bifurcating capillary vessels, an in vitro experiment was performed to perfuse human RBC suspensions into the microfluidic channels with a width of <10 µm. Two types of microchannel geometries were established. One is a single model comprising one parent and two daughter channels with different widths, and the other is a network model that had a symmetric geometry with four consecutive divergences and convergences. In addition to the fractional RBC flux at each bifurcation, changes in hematocrit levels and flow velocity before and after the bifurcation were investigated. In the single model, non-uniform partitioning of RBCs was observed, and this result was in good agreement with that of the empirical model. Furthermore, in the network model, the RBC distribution in the cross-section before the bifurcation significantly affected RBC partitioning in the two channels after the bifurcation. Hence, there was a large RBC heterogeneity in the capillary network. The hematocrit levels between the channels differed for more than one order of magnitude. Therefore, the findings of the current research could facilitate a better understanding of RBC partitioning properties in the microcirculatory system.

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PURPOSE: To analyze the macular microvascular (MMV) architecture, radial peripapillary capillary (RPC) network and choriocapillaris using optical coherence tomography angiography (OCT-A) in patients with systemic sclerosis (SSc) without systemic comorbidities. METHODS: The vessel densities (VDs) of the MMV, foveal avascular zone (FAZ) parameters, choriocapillaris flow areas (CCFAs), RPC VDs, and optic nerve head (ONH) parameters were measured by OCT-A. Retinal thickness and subfoveal choroidal thickness (SFCT) were measured by spectral-domain optical coherence tomography (SD-OCT). The SD-OCT and OCT-A measurements of 53 eyes of 30 SSc patients were compared with 61 eyes of 33 healthy controls. RESULTS: In the MMV analysis, a decrease in the VDs of the superficial capillary plexus and an increase in the FAZ area, FAZ perimeter and non-flow area were detected in the SSc group compared to the controls (P=0.007, P=0.001, P=0.029, P=0.018, and P=0.039, respectively). While there was a decrease in SFCT, no change was found in CCFA (P=0.001 and P=0.902, respectively). The RPC analysis revealed a decrease in the VDs of all vessels for the entire area and the intradisc area, as well as the VDs of the small vessels for the intradisc area (P=0.021, P=0.001, and P=0.003, respectively). In the ONH analysis, there was an increase in the C/D area ratios and cup volumes, and a decrease in the rim areas and nasal quadrant retinal nerve fiber layer thickness (P=0.004, P=0.004, P=0.013, and P=0.032, respectively). CONCLUSION: Decreases in RPC and MMV VDs and changes in ONH parameters were found in OCT-A measurements in patients with SSc.

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Angiogenesis, as part of cancer development, involves hierarchical complicated events and processes. Multiple studies have revealed the significance of the formation and structure of tumor-induced capillary networks. In this study, a discrete mathematical model of angiogenesis is studied and modified to capture the realistic physics of capillary network formation. Modifications are performed on the mathematical foundations of an existing discrete model of angiogenesis. The main modifications are the imposition of the matrix density effect, implementation of realistic boundary and initial conditions, and improvement of the method of governing equations based on physical observation. Results show that endothelial cells accelerate angiogenesis and capillary formation as they migrate toward the tumor and clearly exhibit the physical concept of haptotactic movement. On the other hand, consideration of blood flow-induced stress leads to a dynamic adaptive vascular network of capillaries which intelligibly reflects the brush border effect . The present modified model of capillary network formation is based on the physical rationale that defines a clear mathematical and physical interpretation of angiogenesis, which is likely to be used in cancer development modeling and anti-angiogenic therapies.

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PURPOSE: To quantify the microvasculature density of the optic nerve head (ONH) using optical coherence tomography angiography (OCTA) analysis in patients recovered from Coronavirus Disease 2019 (COVID-19). METHODS: In a comparative cross-sectional, observational study, patients recovered from COVID-19 whose initial diagnosis was confirmed by a rRT-PCR of a nasopharyngeal sample were included in this study. OCTA of ONH was performed in included patients and normal controls. Vascular density (VD) of the all vessels (AV) and small vessels (SV) inside the disc and radial peripapillary capillary (RPC) network density were measured in COVID-19 recovered patients and compared with similar parameters in an age-matched group of normal controls. RESULTS: Twenty-five COVID-19 patients and twenty-two age-matched normal controls were enrolled in the study and one eye per participant was evaluated. The mean whole image SV VD in the COVID-19 group (49.31 ± 1.93) was not statistically significantly different from that in the control group (49.94 ± . 2.22; P = 0.308). A decrease in RPC VD was found in all AV and SV VD measured, which became statistically significant in whole peripapillary SV VD, peripapillary inferior nasal SV VD, peripapillary inferior temporal SV VD, peripapillary superior nasal SV VD, and grid-based AV VD inferior sector (P < 0.05). Inside disc SV VD in the COVID-19 group (49.43 ± 4.96) was higher than in the control group (45.46 ± 6.22) which was statistically significant (P = 0.021). CONCLUSION: Unremarkable decrease was found in ONH microvasculature in patients who had recovered from COVID-19. These patients may be at risk of ONH vascular complications. Increase in inner disc SV VD may be an indicator of ONH hyperemia and edema.

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Background: The perforating arteries in the dorsolateral zone of the midbrain play a crucial role in the functions of the brain stem. Their damage due to herniation, pathological lesions, or surgery, favored by the narrow tentorial incisura, can lead to hemorrhages or ischemia and subsequently to severe consequences for the patient. Objective: In literature, not much attention has been directed to the perforating arteries in the lemniscus; in fact, no reports on the perforators of this anatomical region are available. The present study aims to a detailed analysis of the microanatomy and the clinical implications of these perforators, in relation to the parent vessels. We focused on the small vessels that penetrate the midbrain's dorsolateral surface, known as lemniscal trigone, to understand better their microanatomy and their functional importance in the clinical practice during the microsurgical approach to this area. Methods: Eighty-seven alcohol-fixed cadaveric hemispheres (44 brains) without any pathological lesions provided the material for studying the perforating vessels and their origin around the dorsolateral midbrain using an operating microscope (OPMI 1 FC, Zeiss). Measurements of the perforators' distances, in relation to the parent vessels, were taken using a digital caliper. Results: An origin from the SCA could be found in 70.11% (61) and from the PCA in 27.58% (24) of the hemispheres. In one hemisphere, an origin from the posterior choroidal artery was found (4.54%). No perforating branches were discovered in 8.04% of specimens (7). Conclusion: The perforating arteries of the lemniscal trigone stem not only from the superior cerebellar artery (SCA), as described in the few studies available in literature, but also from the posterior cerebral artery (PCA). Therefore, special attention should be paid during surgery to spare those vessels and associated perforators. A comprehensive understanding of the lemniscal trigone's perforating arteries is vital to avoid infarction of the brainstem when treating midbrain tumors or vascular malformations.