Decrease In Vessel Diameter Research Articles

The Role of Computed Tomographic Angiography in Predicting the Development of Vasospasm Following Ruptured Intracranial Aneurysm Microsurgery.

Introduction Following subarachnoid hemorrhage, cerebral vasospasm is the primary cause of morbidity and death. The aim of this study is to predict the development of vasospasm by detecting changes in vessel diameter after surgery using computed tomography angiography. Methods We retrospectively evaluated the patients who underwent aneurysm clipping due to a bleeding aneurysm between 2019-2022. Age, gender, location, subarachnoid hemorrhage grades, development of perioperative rupture, and temporary clip use were examined. Preoperative and postoperative diameters of the internal carotid artery, A1-A2, and M1-M2 were measured. Radiological and clinical vasospasm development in the postoperative period was also documented. Results The aneurysm localizations of the 100 patients (mean age: 50.38±13.04 years) were anterior cerebral artery in 50 patients, internal carotid artery in 37 patients, and middle cerebral artery in 30 patients. In the postoperative follow-up, radiological vasospasm was apparent in 41 patients. The changes in arterial diameter reveal a statistically significant decrease in the internal carotid artery, M1-M2, and A1-A2 artery diameters on the operated side compared to the contralateral side (p<0.001). Based on the receiver operating characteristic (ROC) analysis, the most likely change in arterial diameter on the operated side to indicate the presence of vasospasm was calculated from the available data, where the decrease in total arterial diameter was 13.7%. Conclusion Vasospasm remains one of the significant causes of morbidity and mortality post subarachnoid hemorrhage. While there have been advances in imaging modalities, predicting which patients will develop vasospasm has remained elusive. Our research attempts to provide a quantifiable metric (13.7% decrease in vessel diameter) that can be an early predictor of this complication.

Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish

The increasing use of cosmetics has raised widespread concerns regarding their ingredients. Cysteamine hydrochloride (CSH) is a newly identified allergenic component in cosmetics, and therefore its potential toxicity needs further elucidation. Here, we investigated the in vivo toxicity of CSH during ocular development utilizing a zebrafish model. CSH exposure was linked to smaller eyes, increased vasculature of the fundus and decreased vessel diameter in zebrafish larvae. Moreover, CSH exposure accelerated the process of vascular sprouting and enhanced the proliferation of ocular vascular endothelial cells. Diminished behavior in response to visual stimuli and ocular structural damage in zebrafish larvae after CSH treatment were confirmed by analysis of the photo-visual motor response and pathological examination, respectively. Through transcriptional assays, transgenic fluorescence photography and molecular docking analysis, we determined that CSH inhibited Notch receptor transcription, leading to an aberrant proliferation of ocular vascular endothelial cells mediated by Vegf signaling activation. This process disrupted ocular homeostasis, and induced an inflammatory response with neutrophil accumulation, in addition to the generation of high levels of reactive oxygen species, which in turn promoted the occurrence of apoptotic cells in the eye and ultimately impaired ocular structure and visual function during zebrafish development.

What Is the Minimum Number of Sutures for Microvascular Anastomosis during Replantation?

As vessel diameter decreases, reperfusion after anastomosis becomes more difficult. When a blood vessel is sutured, its inner diameter becomes narrower owing to the thickness of the suture material and the number of sutures. To minimize this, we attempted replantation using a 2-point suture technique. We reviewed cases of arterial anastomosis in vessels with a diameter of less than 0.3 mm during replantation performed over a four-year period. In all cases, close observation was followed by absolute bed rest. If reperfusion was not achieved, a tie-over dressing was applied, and hyperbaric oxygen therapy was administered in the form of a composite graft. Of the 21 replantation cases, 19 were considered successful. Furthermore, the 2-point suture technique was performed in 12 cases, of which 11 survived. When three or four sutures were performed in nine patients, eight of these cases survived. Composite graft conversion was found in three cases in which the 2-point suture technique was used, and two of these cases survived. The survival rate was high in cases where 2-point sutures were used, and there were few cases of conversion to a composite graft. Reducing the number of sutures aids in optimizing reperfusion.

Rose Bengal Induced Photothrombosis in CAM Integrated Human Split Skin Grafts—A Feasibility Study

Wound healing is a complex process requiring an adequate supply of the wound area with oxygen and nutrients by neo-vascularization, to renew tissue. Local ischemia can result in the formation of chronic wounds. Since there is a lack of wound healing models for ischemic wounds, we aimed to develop a new one, based on chick chorioallantoic membrane (CAM) integrated split skin grafts and induction of ischemia with photo-activating Rose Bengal (RB) in a two-part study: (1) investigation of the thrombotic effect of photo-activated RB in CAM vessels and (2) investigation of the influence of photo-activated RB on CAM integrated human split skin xenografts. In both study phases, we observed a typical pattern of vessel changes after RB activation with a 120 W 525/50 nm green cold light lamp in the region of interest: intravascular haemostasis and a decrease in vessel diameter within 10 min of treatment. In total, the diameter of 24 blood vessels was measured before and after 10 min of illumination. Mean relative reduction of vessel diameter after treatment was 34.8% (12.3%-71.4%; p < 0.001). The results indicate that the present CAM wound healing model can reproduce chronic wounds without inflammation due to the statistically significant reduction of blood flow in the selected area using RB. Combined with xenografted human split skin grafts, we established the set up for a new chronic wound healing model for the research of regenerative processes following ischemic damage of the tissue.

Optička koherentna tomografija sa angiografijom kod pacijenata obolelih od dijabetes melitusa tip 2

Introduction: Diabetic Retinopathy (DR) is a common microvascular complication of diabetes mellitus. Optical Coherence Tomography Angiography (OCTA) is a new method for visualizing the microvasculature of the retina and choroid, which is based on detecting the movement of circulating erythrocytes. Objective: To present OCTA findings in patients with diabetes mellitus with different microvascular changes to diagnose diabetic retinopathy before the onset of clinical signs of the disease, as well as to monitor changes in clinically visible retinopathy, with or without Diabetic Macular Edema (DME). Methods: In this study, OCTA findings were compared in three groups of selected subjects - 5 patients with Non-Proliferative Diabetic Retinopathy (NPDR) without DME, 5 patients with NPDR and DME, and 5 patients with diabetes but without NPDR and DME. Results: Patients in all three groups showed decreased vessel diameter (VD) in the foveal, parafoveal, and perifoveal segments of the Superficial Capillary Plexus (SCP) and Deep Capillary Plexus (DCP) and an increase in Foveal Avascular Zone (FAZ). Conclusion: OCT angiography represents a new technique for visualizing and quantifying vascular changes and is increasingly important in the early diagnosis of subclinical retinopathy, as well as in monitoring existing changes in the retina in people with type 2 diabetes mellitus.

CSF Dynamics: Implications for Hydrocephalus and Glymphatic Clearance.

Beyond its neuroprotective role, CSF functions to rid the brain of toxic waste products through glymphatic clearance. Disturbances in the circulation of CSF and glymphatic exchange are common among those experiencing HCP syndrome, which often results from SAH. Normally, the secretion of CSF follows a two-step process, including filtration of plasma followed by the introduction of ions, bicarbonate, and water. Arachnoid granulations are the main site of CSF absorption, although there are other influencing factors that affect this process. The pathway through which CSF is through to flow is from its site of secretion, at the choroid plexus, to its site of absorption. However, the CSF flow dynamics are influenced by the cardiovascular system and interactions between CSF and CNS anatomy. One, two, and three-dimensional models are currently methods researchers use to predict and describe CSF flow, both under normal and pathological conditions. They are, however, not without their limitations. "Rest-of-body" models, which consider whole-body compartments, may be more effective for understanding the disruption to CSF flow due to hemorrhages and hydrocephalus. Specifically, SAH is thought to prevent CSF flow into the basal cistern and paravascular spaces. It is also more subject to backflow, caused by the presence of coagulation cascade products. In regard to the fluid dynamics of CSF, scar tissue, red blood cells, and protein content resulting from SAH may contribute to increased viscosity, decreased vessel diameter, and increased vessel resistance. Outside of its direct influence on CSF flow, SAH may result in one or both forms of hydrocephalus, including noncommunicating (obstructive) and communicating (nonobstructive) HCP. Imaging modalities such as PC-MRI, Time-SLIP, and CFD model, a mathematical model relying on PC-MRI data, are commonly used to better understand CSF flow. While PC-MRI utilizes phase shift data to ultimately determine CSF speed and flow, Time-SLIP compares signals generated by CSF to background signals to characterizes complex fluid dynamics. Currently, there are gaps in sufficient CSF flow models and imaging modalities. A prospective area of study includes generation of models that consider "rest-of-body" compartments and elements like arterial pulse waves, respiratory waves, posture, and jugular venous posture. Going forward, imaging modalities should work to focus more on patients in nature in order to appropriately assess how CSF flow is disrupted in SAH and HCP.

A theoretical model for the Fåhræus effect in medium–large microvessels

This paper presents a mathematical model capable to reproduce a celebrated phenomenon in blood microcirculation known as Fåhræus effect, since its discovery by Robin Fåhræus (1929). This consists in a decaying of the relative hematocrit in small vessels as the vessel diameter decreases. The key point of the model is a formula, direct consequence of the basic principles of fluid dynamics, that links the relative hematocrit to the reservoir hematocrit and the vessel diameter, which confirms the observed behavior. To test the model we selected, among the few experiments carried on since then, those performed by Barbee and Cokelet (1971). The agreement is remarkable. An extended comparison is also carried out with a celebrated empirical formula proposed by Pries et al. (1992) to describe the same phenomenon.

Vascular topology and blood flow are acutely impacted by experimental febrile status epilepticus

Febrile status epilepticus (FSE) is an important risk factor for temporal lobe epilepsy and early identification of those at high risk for epilepsy is vital. In a rat model of FSE, we identified an acute (2 hrs) novel MRI signal where reduced T2 relaxation values in the basolateral amygdala (BLA) predicted epilepsy in adulthood; this T2 signal remains incompletely understood and we hypothesized that it may be influenced by vascular topology. Experimental FSE induced in rat pups reduced blood vessel density of the cortical vasculature in a lateralized manner at 2 hrs post FSE. Middle cerebral artery (MCA) exhibited abnormal topology in FSE pups but not in controls. In the BLA, significant vessel junction reductions and decreased vessel diameter were observed, together with a strong trend for reduced vessel length. Perfusion weighted MRI (PWI) was acutely increased cerebral blood flow (CBF) in cortex, amygdala and hippocampus of FSE pups that correlated to decreased T2 relaxation values compared to controls. This is consistent with increased levels of deoxyhemoglobin associated with increased metabolic demand. In summary, FSE acutely modifies vascular topological and CBF in cortex and BLA that may underlie acute MRI signal changes that predict progression to future epilepsy.

Abstract 5071: Novel approach to intra- and peri-tumoral delivery of sustained-release chemotherapeutics

Abstract INTRODUCTION: Intratumoral phenylephrine (α1 vasoconstrictor) combined with chemotherapy has been used for cutaneous malignancies with modest local response. The purpose of this study was to improve the efficacy of intratumoral melphalan using sustained-release, liposomal nanoparticles containing phenylephrine in a mouse model of melanoma. METHODS: A modified ethanol injection method was used to develop the liposomal phenylephrine nanoparticles. These were injected peri-tumorally to generate a local vasoconstrictive effect intended to “entrap” intratumorally injected melphalan. Drug exposure/dwell time was measured with fluorescent imaging. Mice bearing B16 (subclone F10) melanoma tumors were treated with intratumoral melphalan (20 ug/50 ul) with or without peri-tumoral liposomal phenylephrine (10 ug/50-100 ul x 4-5 injections around the tumor periphery) twice weekly x 3 weeks. RESULTS: UV-Absorbance spectroscopy confirmed encapsulation of phenylephrine within the liposomal nanoparticles with an expected absorbance of 275 nm. The modified ethanol injection method produced liposomal phenylephrine encapsulation of approximately 25%. Peri-tumoral, liposomal phenylephrine caused vasoconstriction of normal surrounding vessels with an approximate 10% decrease in vessel diameter. Our liposomal phenylephrine nanoparticles also led to increased retention of intratumorally injected fluorescently-labeled (FITC) liposomes 24-48 hours after inoculation, using both melanoma (B16) and breast (TUBO/4T1) cell lines orthotopically grown within mice (C57Bl/6 and BALB/c, respectively). The combination of intratumoral melphalan with peri-tumoral phenylephrine resulted in more effective control of tumor growth and a complete tumor response rate of 44.4%, compared to phenylephrine/melphalan only controls (p &amp;lt; 0.01, n=18 per group). However, there was significant adverse reaction with the combination therapy, resulting in ulceration of the injection/tumor site. Ulcers healed about 14 days after completion of treatment. Immunohistochemistry demonstrated increased infiltration of CD11b+ cells into the tumors, suggesting an immune-mediated response in addition to direct chemotoxicity. CONCLUSIONS: Liposomal nanoparticles containing phenylephrine increased retention/dwell time of intratumorally administered melphalan and resulted in superior anti-tumor response. Our preclinical model holds innovative, translational promise for the clinical advancement of intralesional therapies in cutaneous/subcutaneous malignancies. Citation Format: Emmanuel M. Gabriel, Vijay Madamsetty, Deborah Bahr, Jamie Kaplan, Kristopher Attwood, Sanjay Bagaria, Keith Knutson, Debabrata Mukhopadhyay. Novel approach to intra- and peri-tumoral delivery of sustained-release chemotherapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5071.

Analysis of Cerebrovascular Architecture in Experimental Models of Hypertension and Chronic Neuroendocrine Stress

Cerebral small vessel disease and Alzheimer’s disease are leading causes of dementia. Psychological/social stress and associated hypertension are important drivers of brain vascular dysfunction and impaired perfusion. We set out to investigate if chronic neuroendocrine stress and hypertension have adverse effects on cerebrovascular architecture of various brain regions in two rodent models: 1) a rat model where HPA axis activation and hypertension were induced by brain derived neurotrophic factor (BDNF) overexpression in the paraventricular nucleus of the hypothalamus (PVN) for 5 wks, and 2) in a mouse model, where blood pressure and/or corticosterone levels were elevated by subcutaneous infusions of angiotensin II (AngII, 1.5mg/kg/day), adrenocorticotropic hormone (ACTH, 30ug/kg/day) or a combination of AngII and ACTH for 4 weeks. Cerebrovasculature was labeled by transcardiac perfusion of a liposome‑encapsulated fluorescent DiI dye. Brains were fixed in 4% PFA and transparency was increased with the SeeDB method. Vasculature of the hippocampus (HPC), sensory cortex (CTX), and PVN was evaluated using 2‐photon microscopy in 2mm thick coronal brain slices. 3D model of the vasculature was created by Imaris software (Oxford Instruments) yielding parameters such as vascular segment numbers, lengths, diameters, and number of branch points. 3D Euclidean distance mapping (EDM) was used to determine distribution of distances to nearest vessels (DNVs) within the extravascular space as a measure of accessibility to blood supply. We found that vascular densities were markedly elevated in the PVN relative to other brain regions in both rats and mice. In mice, HPC vascular density was significantly lower relative to CTX, whereas in rats, CTX and HPC densities were similar [vascular densities % (rats, mice): PVN:14.6±1.4, 17.0±0.6; CTX: 9.6±0.5, 8.6±0.4; HPC CA: 8.8±0.7, 6.2±0.3; HPC DG: 9.4±0.6, 5.4±0.3]. EDM analysis revealed that the proportion of short (&lt;15μm) vs long DNVs was the highest in the PVN in both rats and mice. Distribution of DNVs shifted to longer distances in the CTX, and the proportion of short vs long DNVs was the lowest in HPC regions indicating an increased vulnerability to hypoperfusion. Interestingly, neuroendocrine stress and hypertension failed to significantly affect vascular densities and DNV statistics in either rats or mice in the analyzed brain regions. However, there was a notable sex difference in distribution of DNVs in HPC CA regions with male rats having a higher proportion of longer distances than females. In addition, analysis of vascular diameter distribution revealed that BDNF treatment decreased vessel diameters in the PVN of both male and female rats, and in the CTX of male, but not female rats. In summary, we found significant region‐specific variability in vascular structure, with the PVN demonstrating a uniquely dense vascular network. Cerebrovascular architecture was fairly resilient to treatments resembling chronic stress‐induced neuroendocrine and cardiovascular responses, but sex differences in HPC vasculature may promote a higher sensitivity to hypoperfusion in male vs female rats.

The effects of dyslipidemia on noise-induced hearing loss in petrochemical workers in the Southwest of Iran.

Research has shown that the decrease in the inner diameter of vessels caused by hyperlipidemia lowers the capacity for blood oxygen delivery to the cochlea. This leads to impaired cochlear metabolism and causes hearing problems. The effects of dyslipidemia on noise-induced hearing loss in workers were examined. This descriptive cross-sectional study was performed on 692 male employees in a petrochemical industry in the southwest of Iran exposed to 85 dB noise. Clinical audiometry and blood sample tests were used to evaluate the hearing and prevalence indices of dyslipidemia (cholesterol, triglyceride, HDL and LDL). The data were analyzed using SPSS software version 25 (p = 0.05). The results showed that the prevalence of dyslipidemia was 24.5% with abnormal relative triglyceride frequency of 49.5%, HDL of 28%, LDL of 33%, and total blood cholesterol level of 37.8%. There was no significant relationship between NIHL and dyslipidemia (p > 0.09). However, the major NIHL drops at different frequencies were in the individuals with dyslipidemia. The parameters age and dyslipidemia increased NIHL odds ratio (95% C.I.) by 1.130 (1.160-1.100) and 1.618 (2.418-1.082) respectively. The rate of hearing loss in individuals with dyslipidemia increases at different frequencies and it leads to an increase of the OR of NIHL in individuals with dyslipidemia. We can control dyslipidemia and its effective factors. The NIHL is more common in people exposed to noise.

Longitudinal Preclinical Imaging Characterizes Extracellular Drug Accumulation After Radiation Therapy in the Healthy and Leukemic Bone Marrow Vascular Microenvironment

Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia. We developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after total body irradiation (TBI). Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements, including tissue wash-in slope (WIStissue) to measure extracellular drug accumulation. We performed L-QMPM imaging on healthy C57BL/6 (WT) mice, as well as mice bearing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Implants had no effects on calvarium dose, and parameters for wild-type untreated mice were stable during imaging. We observed decreased vessel diameter, vessel blood flow, and WIStissue with the onset of AML and ALL. Two to 10 Gy TBI increased WIStissue and vessel diameter 2 days after radiation therapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Increased WIStissue was observed 5 days after 10 Gy TBI or 4 Gy split-dose TBI (2 treatments of 2 Gy spaced 3 days apart). L-QMPM provides stable functional assessments of the BMV. Nonmyeloablative and myeloablative TBI increases extracellular drug accumulation in the leukemic bone marrow 2 to 5 days posttreatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant TBI at doses from 2 Gy to 10 Gy conditions the BMV to improve drug transport to the bone marrow.

Do angiosperm tree species adjust intervessel lateral contact in response to soil drought?

During soil drought (i.e. limited soil water availability to plants), woody species may adjust the structure of their vessel network to improve their resistance against future soil drought stress. Impacts of soil drought on intervessel lateral contact remain poorly understood despite of its significance to xylem transport efficiency and safety. Here, we analysed drought-induced modifications in xylem structures of temperate angiosperm trees with a focus on intervessel lateral contact. Anatomical analyses were performed both in stems of seedlings cultivated under different substrate water availability and annual rings of mature individuals developed during years of low and high soil drought intensities. In response to limited water availability, a decrease in vessel diameter (up to -20%) and simultaneous increase in vessel density (up to +60%) were observed both in seedlings and mature trees. Conversely, there were only small and inconsistent drought-induced changes in intervessel contact frequency and intervessel contact fraction (typically up to ±15%) observed across species, indicating that intervessel lateral contact is a conservative trait. The small adjustments in intervessel lateral contacts were primarily driven by changes in the contact frequencies between neighbouring vessels (i.e. vessel grouping) rather than by changes in proportions of shared cell walls. Our results demonstrate that angiosperm tree species, despite remarkable adjustments in vessel dimensions and densities upon soil drought, exhibit surprisingly invariant intervessel lateral contact architecture.

Inhibition of glycolytic activator PFKFB3 suppresses tumor growth and induces tumor vessel normalization in hepatocellular carcinoma.

Glycolysis emerges as a new therapeutic target for malignancies. The inhibition of glycolytic activator, PFKFB3, repairs tumor endothelial cell function, and normalizing the tumor microenvironment. We aimed to investigate the significance of PFKFB3 in HCC, and the effects of the PFKFB3 inhibitor, PFK15, in HCC tumor cells and tumor endothelial cells. Double immunofluorescent staining of PFKFB3 and CD31 in HCC tissues revealed that high PFKFB3 expression in both tumor cells and tumor endothelial cells was significantly correlated with poor prognosis. Multivariate analysis identified PFKFB3 expression as an independent prognostic factor. PFK15 suppressed proliferation of HCC cell line and tumor endothelial cells in vitro. In a subcutaneous tumor model of the HCC cell line with tumor endothelial cells, PFK15 suppressed tumor growth and induced apoptosis. Moreover, PFK15 treatment induced tumor vessel normalization, decreasing vessel diameter with pericyte attachment and improving vessel perfusion. High PFKFB3 expression in both tumor cells and tumor endothelial cells was identified as a novel prognostic marker in HCC. Targeting PFKFB3 via PFK15 might be a promising strategy for suppressing tumor growth and inducing tumor vessel normalization.

Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain—Brief Report

THBD (thrombomodulin) is part of the anticoagulant protein C-system that acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes. A recombinant soluble form of THBD was shown to have protective effects in different organs, but how the endogenous THBD is regulated during ischemia, particularly in the brain is not known to date. The aim of this study was to investigate the role of THBD, especially in brain endothelial cells, during ischemic stroke. Approach and Results: To induce ischemic brain damage, we occluded the middle cerebral artery of mice. We found an increased endothelial expression of Thbd in the peri-infarct area, whereas in the core of the ischemic tissue Thbd expression was decreased compared with the contralateral side. We generated a novel Cre/loxP-based mouse line that allows for the inducible deletion of Thbd specifically in brain endothelial cells, which worsened stroke outcome 48 hours after middle cerebral artery occlusion. Unexpectedly, we found no signs of increased coagulation, thrombosis, or inflammation in the brain but decreased vessel diameters and impaired angiogenesis in the peri-infarct area that led to a reduced overall vessel length 1 week after stroke induction. Endogenous THBD acts as a protective factor in the brain during ischemic stroke and enhances vessel diameter and proliferation. These previously unknown properties of THBD could offer new opportunities to affect vessel function after ischemia and thereby improve stroke outcome.

Biophysical Characterization of the Leukemic Bone Marrow Vasculature Reveals Benefits of Neoadjuvant Low-Dose Radiation Therapy

Purpose:Although vascular alterations in solid tumor malignancies are known to decrease therapeutic delivery, the effects of leukemia-induced bone marrow vasculature (BMV) alterations on therapeutic delivery are not well known. Additionally, functional quantitative measurements of the leukemic BMV during chemotherapy and radiation therapy are limited, largely due to a lack of high-resolution imaging techniques available preclinically. This study develops a murine model using compartmental modeling for quantitative multiphoton microscopy (QMPM) to characterize the malignant BMV before and during treatment.Methods and Materials:Using QMPM, live time-lapsed images of dextran leakage from the local BMV to the surrounding bone marrow of mice bearing acute lymphoblastic leukemia (ALL) were taken and fit to a 2-compartment model to measure the transfer rate (Ktrans), fractional extracellular extravascular space (Vcc), and vascular permeability parameters, as well as functional single-vessel characteristics. In response to leukemia-induced BMV alterations, the effects of 2 to 4 Gy low-dose radiation therapy (LDRT) on the BMV, drug delivery, and mouse survival were assessed post-treatment to determine whether neoadjuvant LDRT before chemotherapy improves treatment outcome.Results:Mice bearing ALL had significantly altered Ktrans, increased Vec, and increased permeability compared with healthy mice. Angiogenesis, decreased single-vessel perfusion, and decreased vessel diameter were observed. BMV alterations resulted in disease-dependent reductions in cellular uptake of Hoechst dye. LDRT to mice bearing ALL dilated BMV, increased single-vessel perfusion, and increased daunorubicin uptake by ALL cells. Consequently, LDRT administered to mice before receiving nilotinib significantly increased survival compared with mice receiving LDRT after nilotinib, demonstrating the importance of LDRT conditioning before therapeutic administration.Conclusion:The developed QMPM enables single-platform assessments of the pharmacokinetics of fluorescent agents and characterization of the BMV. Initial results suggest BMV alterations after neoadjuvant LDRT may contribute to enhanced drug delivery and increased treatment efficacy for ALL. The developed QMPM enables observations of the BMV for use in ALL treatment optimization.

Effects of transient ischemia‐reperfusion on in vivo mitochondrial fission and fusion in the murine cerebral vasculature

Mitochondria play important roles in the regulation of cerebral circulation. The effects of ischemia with and without reperfusion on mitochondrial morphology have been well documented in different cell types of the brain. However, the time course of these events, an important determinant of mitochondrial targeting, has been understudied due to technical limitations.The aim of this study was to determine how mitochondrial fission and fusion dynamics are affected by ischemia‐reperfusion, in endothelial cells that form the basis of the neurovascular unit.A thinned skull cranial window was implanted in young, male and female (3–6 month old; n = 5) offspring of B6;129S‐Gt(ROSA)26Sortm1(CAG‐COX8A/Dendra‐2)Dcc/J and B6.Cg‐Tg(Tek‐cre) 1Ywa/J mice expressing mitoDendra 2 fluorescent protein in endothelial mitochondria. Two‐photon microscopy was used to visualize the brain vasculature, via RhodamineB Dextran labelled blood plasma and mitoDendra2 simultaneously at 875 nm. After 2 imaging sessions taken 60 minutes apart, animals were allowed to recover. Then, mice were exposed to 30 minutes of ischemia via middle cerebral artery occlusion followed by 4 hours of reperfusion. Additional time‐lapse images were taken between the 2nd and 4th hour of the re‐perfusion period. Three stacks of 50 images, 1 μm apart, were taken of different regions of interests, containing arteries, veins, and capillaries using a 40X objective and a 1X digital zoom; whereas 3X digital zoom was used to take images for the analyses of mitochondrial fission and fusion events. Ischemia‐reperfusion resulted in a prominent vasoconstriction of the pial vasculature (15% decrease in vessel diameter; n = 66 diameter measurements) as well as the disintegration of green mitochondria signal, suggestive of fission. The in‐depth analysis of time‐lapse images (8–12 stacks of images per channel per imaging session per mouse using a 3X digital zoom) is currently ongoing.Overall, we expect to correlate in vivo mitochondrial changes derived by fission and fusion with vascular events in response to ischemia‐reperfusion in large, penetrating arteries and veins as well as in capillaries.Support or Funding InformationAHA 17SDG33410366; U54 GM104940; HL‐093554

Anatomical variation in vascular attributes of wood of Astronium fraxinifolium Schott trees from the soil loan area of a hydroelectric plant and an experimental plantation

The survival of plants is linked to their capacity to respond to environmental selection. Plants may show different wood anatomical features related to survival, such as an increase in parenchyma and decrease in diameter of vessels. The aim of this study was to investigate the wood anatomical features of male and female Astronium fraxinifolium trees growing in environments characterized by degraded and non-degraded soil. It was expected that the trees to present: (i) a response to environment that would allow better hydraulic conductivity, and (ii) a wood anatomy difference according to the species' gender. The results showed that the wood anatomy differed significantly between male and female plants only in the non-degraded area. The male trees had larger rays and fibre lumens, but the fibre wall thickness and length did not differ significantly. Neither nor did the diameter and density of vessels. Comparing the areas, the wood of the impacted area showed vessels of larger diameter and lower density, larger rays and fibres with smaller lumens and thicker walls, but no significant difference in the fibre length. Some wood anatomical features in the impacted area, such as greater vessels, supported by larger rays and thicker fibre walls, were probably influenced by stress at the site. The anatomical features of female trees presented lower values than the male ones in the non-impacted area.

Tiba Induced Morphological and Root Anatomical Changes in Lentil

A field experiment was conducted to evaluate the effect of 2,3,5-triiodobenzoic acid (TIBA) at 0, 10, 20, 30 and 40 ppm on the morphological and root anatomical changes of lentil (Lens culinaris Medik. cv. BARI Mosur-7). Foliarly applied TIBA decreased plant height significantly with the increasing concentrations of TIBA. Significantly maximum number of branches and leaves per plant were recorded due to 10 ppm TIBA treatment. Leaves were darker green in plants receiving 10 ppm TIBA due to high chl-a, -b and low carotenoid contents compared to control. Ten ppm TIBA increased root length significantly and root diameter non-significantly than the control plants. Root diameter in plants treated with 10 ppm TIBA increased due to the increase in the width of the cortex, decrease in vessel diameter and enhancement of the formation of more secondary xylem vessels.&#x0D; Journal of Bangladesh Academy of Sciences, Vol. 43, No. 2, 107-112, 2019

Cerebral vessel anatomy as a predictor of first-pass effect in mechanical thrombectomy for emergent large-vessel occlusion.

Mechanical thrombectomy is effective in acute ischemic stroke secondary to emergent large-vessel occlusion, but optimal efficacy is contingent on fast and complete recanalization. First-pass recanalization does not occur in the majority of patients. The authors undertook this study to determine if anatomical parameters of the intracranial vessels impact the likelihood of first-pass complete recanalization. The authors retrospectively evaluated data obtained in 230 patients who underwent mechanical thrombectomy for acute ischemic stroke secondary to large-vessel occlusion at their institution from 2016 to 2018. Eighty-six patients were identified as having pure M1 occlusions, and 76 were included in the final analysis. The authors recorded and measured clinical and anatomical parameters and evaluated their relationships to the first-pass effect. The first-pass effect was achieved in 46% of the patients. When a single device was employed, aspiration thrombectomy was more effective than stent retriever thrombectomy. A larger M1 diameter (p = 0.001), decreased vessel diameter tapering between the petrous segment of the internal carotid artery (ICA) and M1 (p < 0.001), and distal collateral grading (p = 0.044) were associated with first-pass recanalization. LASSO (least absolute shrinkage and selection operator) was used to generate a predictive model for recanalization using anatomical variables. The authors demonstrated that a larger M1 vessel diameter, low rate of vessel diameter tapering along the course of the intracranial ICA, and distal collateral status are associated with first-pass recanalization for patients with M1 occlusions.