Vessel Perfusion Research Articles

Safety of Cerebral Intra-Arterial Chemotherapy for the Treatment of Malignant Brain Tumours

Background: Cerebral intra-arterial chemotherapy (CIAC) has been demonstrated to achieve tumoricidal concentrations in cerebral tumour cells that are otherwise unachievable due to the presence of the blood–brain barrier. In this study, we sought to analyze the safety of CIAC in a cohort of patients treated at the Centre intégré universitaire de santé et de services sociaux de l’Estrie—Centre hospitalier universitaire de Sherbrooke (CIUSSS-CHUS). Methods: Treatments consisted of monthly CIAC. A neurological examination and neuroimaging study (MRI) were performed before every treatment. The files of patients enrolled in our CIAC programme were reviewed. Adverse events were analyzed and categorized. Results: Overall, 2991 CIAC procedures were performed in 642 patients. Pathologies were as follows: malignant gliomas (68.7%), cerebral metastasis (17.6%), and cerebral lymphomas (13.7%). Perfusion vessels were as follows: 80% internal carotid artery and 20% vertebral artery. The chemotherapeutic agents used were carboplatin (86.4%), methotrexate (28.5%), melphalan (28.6%), and liposomal doxorubicin (2.8%). Osmotic blood–brain barrier disruption (BBBD) was induced in 30.5% of treatments. Symptomatic vascular adverse events occurred during 27 procedures (0.9%) in 26 patients (4%). Namely, 23 strokes, one carotid artery occlusion (responsible for one of the strokes), and two intratumoral and one subdural hemorrhage. The absolute risk of stroke was 1.3% and 0.5% for CIAC with or without BBBD, respectively. The use of the vertebral artery significantly increased the risk of stroke. Drug infusion-related seizures occurred in 2.5% of patients; 83.8% were associated with methotrexate and 16.2% with carboplatin. Conclusions: CIAC is a safe procedure with a 0.9% overall rate of symptomatic complications (stroke, carotid occlusion, subdural hemorrhage or intratumoral bleeding—n = 27/2991) on a treatment basis, mainly consisting of strokes (85%, n = 23), with a modified NIH Stroke Scale score of 4.1 ± 3.3.

Peripapillary and Macular Microvasculature of the Retina in Primary Angle Closure Suspect

Purpose: To compare the macular and peripapillary vascular parameters between the primary angle closure suspect (PACS) eyes and normal control eyes using optical coherence tomography angiography (OCTA).Methods: In this retrospective study, 42 PACS subjects and 38 normal individuals are included. Vessel density (VD) and perfusion density (PD) of the macular area and peripapillary area, and fovea avascular zone parameter were analyzed using OCTA and compared between two groups after adjustment for the axial length.Results: There were no statistically significant differences in sex ratio, age, refractive errors and intraocular pressures between both groups. In the peripapillary area, inferior VD and PD in the outer zone were significantly lower in the PACS eyes, while the retinal nerve fiber layer thicknesses were similar between groups (<i>p</i> = 0.032, 0.026). In the macular superficial capillary plexus, inferior VD and PD in the inner zone, inferior VD and PD, nasal VD and PD in the outer zone were significantly lower in the PACS eyes, whereas ganglion cell inner plexiform layer thickness were similar between both groups (all <i>p</i> < 0.005).Conclusions: The VDs and PDs of retinal capillaries in PACS eyes, which have no glaucomatous changes in the retinal nerve fiber layer and optic nerve disc, were significantly lower compared to normal eyes.

ET-3/ETBR Mediates Na+-Activated Immune Signaling and Kidney Lymphatic Dynamics.

Lymphatic collecting vessels in the kidney are critical in clearing interstitial fluid, macromolecules, and infiltrating immune cells. Dysfunction of the lymphatic vessels can disrupt this process and exacerbate injury-associated inflammation in many disease conditions. We previously found that sodium accumulates within the kidney interstitium during proteinuric kidney injury and elevated sodium environments stimulate isolevuglandin production in antigen-presenting cells, stimulating T cells, and modulating inflammatory responses. In the present study, we investigated whether proteinuric injury increases production of isolevuglandin-adduct formation in antigen-presenting cells, their effects on lymphatic endothelial cells (LECs), and the role of the ET-3 (endothelin-3)/ETBR (endothelin type B receptor) on lymphatic vessel function. We used a mouse model of nephrotoxin-induced proteinuric injury to show that proteinuric injury expanded the kidney lymphatic network and to immunophenotype the infiltrating immune cells. To determine mechanisms, we analyzed the interaction of migratory immune cells and LECs using an in vitro transwell migration assay, bulk RNA sequencing, and flow cytometric analysis. To determine the effect of ET-3/ETBR axis on lymphatic vessel contractility, we analyzed microdissected lymphangions utilizing a vessel perfusion chamber. We found that animals with proteinuric injury have increased kidney lymphangiogenesis, isolevuglandin-producing dendritic cells, and IFN (interferon)-γ-producing CD4+T cells. The sodium avid environment present in kidney injury enhances the interaction between LECs and migratory antigen-presenting cells and LEC production of isolevuglandin-adducts. Elevated sodium environment-induced isolevuglandin-adduct formation facilitates the ET-3/ETBR communication between LECs and dendritic cells. In addition, the ET-3/ETBR axis modulates lymphatic collecting vessel pumping dynamics. These findings reveal a novel mechanism linking the isolevuglandin-mediated ET-3/ETBR axis with LECs and infiltrating dendritic cells. ET-3/ETBR signaling in lymphatic vessel dynamics is a novel pathogenic component and a possible therapeutic target in kidney disease.

Retinal Neurovascular Impairment in Full-Course Diabetic Retinopathy: The Guangdong Diabetic Retinopathy Multiple-Omics Study.

The purpose of this study was to explore the succession of the central and peripheral neurovascular and microstructural impairments in patients with full-course diabetic retinopathy (DR), consisting of preclinical DR, nonproliferative DR (NPDR), and proliferative DR (PDR). Our analysis included 81 participants (including 23 healthy controls, 23 with preclinical DR [diabetes without retinopathy], 13 with NPDR, and 22 with PDR) from the Guangdong Diabetic Retinopathy Multiple Omics Study. Retinal structure and function were evaluated and quantified using ultra-widefield swept-source optical coherence tomography angiography (UWF-SS-OCTA), electroretinography (ERG), and adaptive optics scanning laser ophthalmoscopy (AOSLO). Correlation analysis was conducted to explore the relationship between structural parameters and functional parameters. In the preclinical DR group, decreased amplitude in the DR assessment protocol were observed (P = 0.003), with no changes in structure and photoreceptor cells (all P > 0.05). In the NPDR group, photoreceptor cells were impaired (all P < 0.05) with delayed implicit time in the International Society for Clinical Electrophysiology of Vision (ISCEV) Photopic flicker protocol, increased macular and inner nuclear layer thickness, and decreased vessel density and perfusion area of the deep capillary plexus (all P < 0.05). In the PDR group, delayed implicit time and decreased amplitude in the ISCEV Photopic flicker and photopic negative response (PhNR) protocol, and neurovascular impairments were observed (all P < 0.05). Correlation analysis demonstrated a significant correlation between functional parameters and various structural indicators (all P < 0.05). The cone pathway function began to decline in preclinical DR and distinct photoreceptor cell disorders were observed in NPDR. Notably, instruments with a wider field of view or more detailed microscopic techniques will provide enhanced neurovascular imaging, offering fresh insights into full-course DR.

GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders.

Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported. GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3βADKO and GSK3αADKO). A comprehensive whole-body metabolism analysis was performed on obese GSK3βADKO mice induced by a high-fat diet. RNA sequencing was conducted on AT of both obese GSK3βADKO and GSK3αADKO mice. Various analyses, including vessel perfusion studies, lipolysis analysis, multiplex protein assays, in vitro protein phosphorylation assays, and whole-mount histology staining, were performed on AT of obese GSK3βADKO mice. Tube-formation experiments were performed using 3B-11 endothelial cells cultured in the conditional medium of matured adipocytes under hypoxic conditions. Chromatin precipitation and immunofluorescence studies were conducted using cultured adipocytes with GSK3 inhibition. Our findings provide the first evidence that adipocyte-specific knockout of GSK3β expands AT vascularization and mitigates obesity-related metabolic disorders. GSK3β deficiency, but not GSK3α, in adipocytes activates AMPK (AMP-activated protein kinase), leading to increased phosphorylation and nuclear accumulation of HIF-2α, resulting in enhanced transcriptional regulation. Consequently, adipocytes increased VEGF (vascular endothelial growth factor) expression, which engages VEGFR2 on endothelial cells, promoting angiogenesis, expanding the vasculature, and improving vessel perfusion within obese AT. GSK3β deficiency promotes AT remodeling, shifting unhealthy adipocyte function toward a healthier state by increasing insulin-sensitizing hormone adiponectin and preserving healthy adipocyte function. These effects lead to reduced fibrosis, reactive oxygen species, and ER stress in obese AT and improve metabolic disorders associated with obesity. Deletion of GSK3β in adipocytes activates the AMPK/HIF-2α/VEGF/VEGFR2 axis, promoting vasculature expansion within obese AT. This results in a significantly improved local microenvironment, reducing inflammation and effectively ameliorating metabolic disorders associated with obesity.

Nailfold videocapillaroscopy – a novel method for the assessment of hemodynamic incoherence on the ICU

BackgroundLoss of hemodynamic coherence is a phenomenon in critically ill patients. Due to inflammatory events and endothelial remodeling, macro- and microhemodynamics are decoupled from each other, resulting in microcirculatory disturbances and end organ ischemia despite adequate vital parameters. So far, quantification of perfusion of vessels with < 100 μm diameter on the intensive care unit (ICU) was regularly performed with incident darkfield (IDF) microscopy. Nailfold videocapillaroscopy (NVC), however, is an established and easy method for visualization of the microcirculation in chronic diseases. We here evaluated NVC in critically ill patients and compared its use with consensus microcirculatory assessment of IDF-microscopy.MethodsA new score, the capillary microcirculation (CapMic) score summarizing the microcirculation of the nail fold at four regions of digitus III, IV and V in a number between 0 (= no microcirculation) and 1 (= completely preserved microcirculation) was first established in 10 healthy volunteers and compared to the Microangiopathy Evolution Score (MES) standardized for NVC in chronic diseases. Then, n = 60 critically ill patients were recruited from a surgical ICU. Consensus-defined IDF scores and NCV data were compared at a single time point.ResultsEvaluation of the CapMic score in 10 healthy volunteers at rest and under iatrogenic limb ischemia showed robust changes (0.80 ± 0.03 vs. 0.51 ± 0.12, p < 0.001). In critically ill patients, the IDF microscopy parameters “proportion of perfused vessels” (PPV) and “microvascular flow index” (MFI) inversely correlated with the MES (Spearman’s R = -0.590, p < 0.001; Spearman’s R = −0.585, p < 0.001). There was a positive correlation between PPV and the CapMic score (Spearman’s R = 0.714, p < 0.001) and between MFI and the CapMic score (Spearman’s R = 0.711, p < 0.001) and an inverse correlation between MES and the CapMic score (Spearman’s R = −0.610, p < 0.001). Both sublingual and nailfold microcirculation deteriorated under rising norepinephrine- and crystalloid volume-requirements.ConclusionNVC-imaging provides comparable information on the microcirculation in critically ill patients compared to sublingual IDF microscopy. NCV could represent a new, additional method for diagnosing microcirculatory parameters on the ICU.

Angioarchitectural alterations in the retina and choroid in frontotemporal dementia.

Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder that affects the frontal and temporal lobes of the brain, leading to cognitive decline and personality changes. The objective of this cross-sectional study was to characterize angioarchitectural changes in the retina and choroid of individuals with FTD compared to cognitively normal controls using optical coherence tomography (OCT) and OCT angiography (OCTA). Cross-sectional comparison of patients with FTD and controls with normal cognition. All participants underwent Mini-Mental State Examination (MMSE) at the time of imaging. Outcome measures included OCT parameters: retinal nerve fiber layer (RNFL) thickness, ganglion cell layer-inner plexiform layer (GC-IPL) thickness, central subfield thickness (CST), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI); and OCTA superficial capillary plexus parameters: foveal avascular zone (FAZ) area, 3x3mm and 6x6mm macular perfusion density (PD) and vessel density (VD), 4.5x4.5mm peripapillary capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equation analysis was used to account for the inclusion of 2 eyes from the same participant. 29 eyes of 19 patients with FTD and 85 eyes of 48 controls were analyzed. In FTD, 3x3mm macular PD (p = 0.02) and VD (p = 0.02) and CFI (p = 0.01) were reduced compared to controls. There was no difference in average 4.5x4.5mm CPD, RNFL thickness, GC-IPL thickness, CST, SFCT, CVI, FAZ, or 6x6mm VD or PD between FTD and controls (all p > 0.05); however, there was a trend toward lower macular 6x6mm PD and VD in patients with FTD. Decline of peripapillary and macular OCT and OCTA parameters merit further investigation as potential biomarkers for FTD detection. Noninvasive retinal and choroidal imaging may hold promise for earlier detection, and future longitudinal studies will clarify their role in monitoring of FTD.

Hemodynamic analysis on the flow characteristics around abdominal aortic hemorrhage site

The hemodynamic characteristics of blood flow around the site of abdominal aortic hemorrhage can serve as a valuable indicator for identifying the location of hemorrhage. In this research, we conducted numerical simulations to analyze the flow fields in the patient-specific abdominal aorta with and without hemorrhage. We quantitatively compared differences in flow field patterns, blood loss, and branch vessel perfusion between hemorrhagic and non-hemorrhagic cases. Our numerical results demonstrate that there is a distinct hemodynamic characteristic observed around the hemorrhage site, characterized by continuous abnormal high-velocity (&amp;gt;0.7 m/s) and high-Rortex (&amp;gt;200) zone. Additionally, we evaluated the amount of blood loss and time to moderate shock for different cases of abdominal aortic hemorrhage, while statistically analyzing variations in branch vessel perfusion along the abdominal aorta. These findings provide quantitative estimations for blood loss, branch perfusion, and potential indicators to assess rescue time window as well as evaluate the extent of distal tissue damage and organ injury.

Effects of veno-arterial extracorporeal membrane oxygenation return cannula side hole structure on aortic hemodynamic features under different perfusion levels.

The interaction between primary left ventricular output and Veno-arterial extracorporeal membrane pulmonary oxygenation (VA ECMO) flow may impede the perfusion of aortic vessels with hyperoxic blood, leading to differential oxygenation. ECMO return cannula design significantly influences the perfusion level of blood supplied via ECMO. This study aimed to investigate the impact of various cannula designs (side hole number) on intravascular flow patterns under different blood perfusion conditions. Six return cannula models with different side hole number and three cardiac output waveforms were designed based on clinical data for comparative analysis. The position of the blood mixing zone (MZ) was influenced by the flow-volume ratio of the heart output (CO/(CO+Qec)) and cannula design. As the CO/(CO+Qec) and the number of side holes in the cannula increased, the MZ shifted from the ascending aorta to the descending aorta. Concurrently, aortic wall and scalar shear stress on the impact side of ECMO cannulation reduced progressively. Return cannula with side holes effectively mitigated discrepancies in the perfusion of the renal artery and inadequate perfusion of the lower limb vessels on the cannula side while simultaneously reducing damage to the vessel walls and blood. However, increasing the number of side holes in the return cannulas resulted in diminished perfusion of the aortic arch bifurcation vessels by hyperoxic blood supplied via ECMO. Increasing the number of return cannula side holes for VA ECMO femoral artery cannulation improves hypoxic perfusion in the lower limb and reduces vascular endothelial injury, but may also lead to inadequate hypoxic perfusion in the upper body.

Quantitative detection of macular microvascular abnormalities identified by optical coherence tomography angiography in different hematological diseases

It is now understood that hematological diseases can have detrimental effects on the retina, reducing retinal capillaries, compromising visual function, and potentially causing irreversible visual impairment. Over the years, there has been limited research on macular microvascular abnormalities, such as changes in vessel density and the foveal avascular zone (FAZ) and variations in the severity of these effects across different types of blood disorders. This study aims to quantitatively assess the impact of various hematological disorders on the retina using optical coherence tomography angiography (OCTA). Compared with healthy eyes, patients with different blood diseases exhibited reductions in linear vessel density (LVD), perfusion vessel density (PVD), FAZ area, and FAZ perimeter. Notably, patients with erythrocyte diseases showed more significant abnormalities in LVD and PVD, while patients with lymphocytic diseases demonstrated more pronounced abnormalities in the FAZ area and perimeter. OCTA imaging could potentially reflect changes of the retinal microvascular of patients with hematological diseases and may serve as a valuable tool for distinguishing abnormalities affecting different blood cell lines. This approach offers a novel avenue for assessing, treating, and monitoring blood disorders.

Neuroendoscopy Training

AbstractNeuroendoscopy can be learnt by assisting or doing live human surgery, cadaver dissection with or without augmented pulsatile vessel and cerebrospinal fluid (CSF) perfusion, and practicing on live animal, dead animal model, synthetic models, three-dimensional printing model with or without augmentation with animal, cadaver tissue, pulsatile vessel and reconstructed CSF model, virtual reality (VR) simulator, and hybrid simulators (combined physical model and VR model). Neurosurgery skill laboratory with basic and advanced learning should be there in all teaching hospitals. Skills can be transferred from simulation model or VR to cadaver to live surgery. Staged learning (first with simple model to learn basic endoscopic technique, then animal model, and then augmented cadavers) is the preferred method of learning. Although most surveys favor live surgery and practice on animal models and cadavers as the most preferred training model now, in future VR may also become a favored method of learning. This article is based on our experience in over 10,000 neuroendoscopic surgeries, and feedback from over 950 neuroendoscopic fellows or consultants who attended workshops conducted every 6 monthly since 2010. A literature search was done on PubMed and Google Scholar using (neuroendoscopy) AND (learning), and (neuroendoscopy) AND (training), which resulted in 121 and 213 results, respectively. Out of them, 77 articles were finally selected for this article. Most of the training programs typically focus on microneurosurgical training. There is lack of learning facilities for neuroendoscopy in most centers. Learning of neuroendoscopy differs greatly from microneurosurgery; switching from microneurosurgery to neuroendoscopy can be challenging. Postgraduate training centers should have well-equipped neuroendoscopy skill laboratory and the surgical educational curriculum should include neuroendoscopy training. Learning endoscopy is about taking advantages of the technique and overcoming the limitations of endoscopy by continuous training.

Losartan rewires the tumor-immune microenvironment and suppresses IGF-1 to overcome resistance to chemo-immunotherapy in ovarian cancer.

Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors. Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells. Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.

The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.

Reversal of ischemia is mediated by neo-angiogenesis requiring endothelial cell (EC) and pericyte interactions to form stable microvascular networks. We describe an unrecognized role for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in potentiating neo-angiogenesis and vessel stabilization. We show that the endothelium is a major source of TRAIL in the healthy circulation compromised in peripheral artery disease (PAD). EC deletion of TRAIL in vivo or in vitro inhibited neo-angiogenesis, pericyte recruitment, and vessel stabilization, resulting in reduced lower-limb blood perfusion with ischemia. Activation of the TRAIL receptor (TRAIL-R) restored blood perfusion and stable blood vessel networks in mice. Proof-of-concept studies showed that Conatumumab, an agonistic TRAIL-R2 antibody, promoted vascular sprouts from explanted patient arteries. Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.

Retinal microcirculation changes in prediabetic patients with short-term increased blood glucose using optical coherence tomography angiography.

Retinal microcirculation alterations are early indicators of diabetic microvascular complications. Optical coherence tomography angiography (OCTA) is a noninvasive method to assess these changes. This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA. To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA. Fifty volunteers were divided into three groups: Group 1 [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)], Group 2 (both IFG and IGT), and a control group. Retinal microcirculation parameters, including vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics, were measured using OCTA. Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states. One hour after glucose intake, the central VD (P = 0.023), central PD (P = 0.026), and parafoveal PD (P < 0.001) were significantly greater in the control group than in the fasting group. In Group 1, parafoveal PD (P < 0.001) and FAZ circularity (P = 0.023) also increased one hour after glucose intake. However, no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake (P > 0.05). Compared with the control group, Group 1 had a larger FAZ area (P = 0.032) and perimeter (P = 0.018), whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Compared with Group 1, Group 2 had greater central VD (P = 0.013) and PD (P = 0.008) and a smaller FAZ area (P = 0.012) and perimeter (P = 0.010). One hour after glucose intake, Group 1 had a larger FAZ area (P = 0.044) and perimeter (P = 0.038) than did the control group, whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Group 2 had greater central VD (P = 0.042) and PD (P = 0.022) and a smaller FAZ area (P = 0.015) and perimeter (P = 0.016) than Group 1. At fasting, central PD was significantly positively correlated with blood glucose levels (P = 0.044), whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake. A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

Optical coherence tomography angiography analysis of the fellow eye in unilateral pseudoexfoliation syndrome

PurposeTo compare the macular and optic disc vascular parameters in the unaffected fellow eyes of subjects with unilateral pseudoexfoliation syndrome (PXS) and controls using optical coherence tomography angiography (OCTA).MethodsThe medical records of 61 eyes of 61 patients were analyzed in a retrospective study. Of these, 30 eyes were unaffected fellow eyes and 31 eyes were control eyes. The vessel density (VD), perfusion density (PD) and foveal avascular zone (FAZ)-related parameters of the superficial capillary plexus (SCP) in the circumpapillary and macular area and the VD and PD of the deep capillary plexus (DCP) in the macular area were measured using OCTA after dilatation and were compared between two groups after adjustment for age, sex and axial length.ResultsThere were no statistically significant differences in sex ratio or mean age, central corneal thickness measurements, refractive errors, intraocular pressures and axial length between both groups (all P > 0.05). In the circumpapillary area, inferior VD and PD in the inner zone, as well as average, temporal, inferior, and nasal VD and PD in the outer zone were significantly reduced in the unaffected fellow eyes with unilateral PXS, while the circumpapillary retinal nerve fiber layer (RNFL) thicknesses were similar between groups. In the macular SCP, VDs were significantly lower in all sectors in the inner area and in the outer zones (p < 0.05 for all), PDs were significantly lower in all sectors (p < 0.05 for all) except the nasal sector of the outer zone (p = 0.003 for average, p = 0.029 for superior sector, p = 0.004 for temporal sector, p < 0.001 for inferior sector), and the FAZ circularity (p = 0.037) were significantly lower in the unaffected fellow eyes with unilateral PXS, whereas macular ganglion cell inner plexiform layer (GCIPL) thickness was similar between the two groups.ConclusionsAlthough circumpapillary RNFL and GCIPL thicknesses were similar between the two groups, VDs and PDs in the circumpapillary and macular SCP and FAZ circularity were significantly lower in the fellow eye of subjects with unilateral PXS.

Macular, Choroidal, and Peripapillary Perfusion Changes in Mild and Moderate Traumatic Brain Injury Using Optical Coherence Tomography and Angiography.

Introduction: To compare the retinal and choroidal architecture and microvasculature between patients with mild or moderate traumatic brain injury (TBI) and controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: Patients with a documented history of TBI, and age-matched and sex-matched controls were recruited. The primary outcome measures were differences between OCT parameters, including the choroidal vascularity index, and between OCTA superficial capillary plexus metrics, including foveal avascular zone (FAZ) circularity, 3.0 mm × 3.0 mm and 6.0 mm × 6.0 mm macular vessel density and perfusion density, and 4.5 mm × 4.5 mm peripapillary capillary perfusion density and capillary flux index. Results: Sixty-seven eyes of 36 patients with TBI and 72 eyes of 36 control patients met the inclusion criteria. Twelve patients (33.3%) had a diagnosis of mild TBI without loss of consciousness (LOC), 21 (58.3%) had mild TBI with LOC, and 3 (8.3%) had moderate TBI. There was a significant reduction in FAZ circularity and in 3.0 mm × 3.0 mm macular OCTA vessel density and perfusion density in patients with TBI. In cases with TBI associated with posttraumatic stress disorder, all macular OCTA parameters were significantly reduced. There was an increase in the choroidal vascularity index across the severity of TBI; however, it was reduced in those with more than 1 TBI (P = .03). Conclusions: There was a reduction in macular perfusion in eyes of patients with mild or moderate TBI. The choroidal vascularity index helps differentiate subtle effects of more severe or mild repeated TBI. Further prospective investigation will evaluate OCT imaging and OCTA imaging as a noninvasive screening modalities to assess changes in retinal and choroidal microvasculature.

Cardio-ocular syndrome: Retinal microvascular changes in acutely decompensated heart failure.

To investigate the changes in retinal microvasculature by contemporary imaging techniques during episodes of acute decompensated heart failure (ADHF) and following recompensation compared to age-matched controls without known cardiac or retinal disease. Adult patients hospitalized with a primary diagnosis of ADHF, regardless of left ventricular ejection fraction (LVEF) and treated with a minimum dose of 40 mg of intravenous furosemide or equivalent were included. Transthoracic echocardiography was conducted in all patients. Eye examinations were performed out within the initial 24 h after admission and after recompensation before discharge. All eyes underwent a general examination, including a best corrected visual acuity test, dilated fundoscopy, spectral-domain optical coherence tomography (OCT) as well as OCT angiography (OCT-A). In addition, 40 participants without documented cardiac or retinal diseases served as controls. Forty patients with ADHF (mean age 78.9 ± 8.8 years; 32% female) with a mean LVEF of 43 ± 12.8% were included. All patients were treated with intravenous diuretics for a median of 4.3 ± 2.8 days. There was a significant reduction in N-terminal pro-B-type natriuretic peptide from baseline up to discharge (10 396 [interquartile range 6410] vs. 6380 [interquartile range 3933] pg/ml, p ≤ 0.001) and inferior vena cava diameters (2.13 ± 0.4 vs. 1.63 ± 0.3 cm, p = 0.003). Compared to the control group, patients with ADHF showed on admission impaired visual acuity (0.15 ± 0.1 vs. 0.35 ± 0.1 logMAR, p < 0.001), reduced macular vessel density (18.0 ± 1.9 vs. 14.3 ± 3.6 mm/mm2, p < 0.001) and perfusion density (42.6 ± 3.2 vs. 35.2 ± 9.7%, p < 0.001). After recompensation, the mean overall vessel density and mean overall perfusion density were markedly increased at discharge (14.3 ± 3.6 vs. 19.7 ± 2.6 mm/mm2, p = 0.001, and 35.2 ± 9.7 vs. 39.2 ± 6.5%, p = 0.005, respectively). The mean diameter of the superior temporal retinal vein at admission was significantly larger compared to the control group (136 ± 19 vs. 124 ± 22 μm, p = 0.008) and decreased significantly to 122 ± 15 μm at discharge (p < 0.001). This analysis revealed a remarkable reversible change in retinal microvasculature after ADHF. This could provide a valuable evidence for use of OCT-A in the assessment of overall microperfusion and haemodynamic status in patients with acute heart failure.

Perfusion deficit and vessel wall characteristics to predict recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion.

To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.

Non-invasive follow-up for intracranial aneurysms treated with contour neurovascular system-comparison of digital subtraction angiography (DSA) to magnetic resonance imaging (MRI) and spectral computed tomography angiography (CTA) in vitro.

The contour neurovascular system (CNS) is an intrasaccular flow-disrupting device designed for the treatment of intracranial wide-necked bifurcation aneurysms. Metal artifacts limit magnetic resonance imaging (MRI) accessibility after implantation. The purpose of this in vitro study was to evaluate non-invasive imaging alternatives to digital subtraction angiography (DSA). Three aneurysms of patients originally treated with CNS were three-dimensional (3D)-printed (one at the basilar tip and two at the middle cerebral artery bifurcation). CNS devices were implanted under fluoroscopic control into the 3D models. Post-implantation two-dimensional-DSA, flat panel computed tomography angiography (CTA), MRI, and spectral CTA were performed. Time of flight angiography and T1 weighted sequences showed large susceptibility artifacts at the detachment zone of the devices. A thin-sliced T2 weighted sequence in cross-sectional orientation to the aneurysm allowed visualization of the aneurysm dome, but the aneurysm neck and parent vessel could not be assessed. Focused spectral CTA, especially a 40 keV reconstruction with a metal artifact reduction algorithm (orthopedic metal artifact reduction (OMAR)), showed only minor artifacts at the detachment zone. This approach achieved a very similar result to DSA and flat panel computed tomography, enabling the assessment of the device structure, aneurysm perfusion, and parent vessel perfusion. For non-invasive follow-up of CNS, focused 40 keV CTA with OMAR seems to be a valuable option. MRI can be valuable for larger aneurysms to assess the aneurysm dome, but was not suitable for evaluating the parent vessels and aneurysm neck after CNS implantation in this study.

Prolonged inhibition of intratumoral mast cells enhances efficacy of low-dose antiangiogenic therapy.

Low-dose antiangiogenic therapies have demonstrated the ability to enhance normalization of tumor vessels, consequently improving hypoxia levels, drug delivery, and promoting anticancer immune responses. Mast cells have been identified as contributors to resistance against antiangiogenic therapy and facilitators of abnormal neoangiogenesis. In this study, we demonstrate that by simultaneously targeting intratumoral mast cells with Imatinib and administering low-dose anti-VEGFR2 therapy, antitumor efficacy can be enhanced in preclinical models. Thus, combinatory treatment overcomes therapy resistance, while concurrently promoting tumor vessel normalization. Notably, histomorphometric analysis of tumor sections revealed that vessel perfusion could be improved through mast cell inhibition and, despite a significantly reduced microvessel density, the combination treatment did not result in elevated tumor hypoxia levels compared to anti-VEGFR2 therapy alone. Short-term Imatinib application effectively increased antitumor efficacy, and by prolonging the application of Imatinib tumor vessel normalization was additionally improved. The combination of mast cell depletion and antiangiogenic treatments has not been investigated in detail and promises to help overcoming therapy resistance. Further studies will be required to explore their impact on other treatment approaches, and subsequently to validate these findings in a clinical setting.