Vessel Caliber Research Articles

Abstract 159: Computed Tomography Angiography Negative Spinal Artery Dissection

Introduction Vertebral artery dissection (VAD) is a relatively common cause of ischemic stroke, especially after chiropractic neck manipulation. VAD usually can be diagnosed by noninvasive imaging studies such as CT angiography (CTA) of the head and neck with suggestive findings of an arterial string sign, arterial stenosis, a double lumen sign, a pseudoaneurysm, or an occlusion. However, in rare situations, CTA may display normal arterial caliber except for very subtle signs such as abnormal dorsal thickening of the arterial wall against adjacent fat at the V3 segment of the vertebral artery. This is referred to as the "suboccipital rind sign." Here we wish to report such a case as identified at our institution. Methods Electronic charts of a patient with acute spinal shock and strokes were reviewed. Results The patient is a 36‐year‐old female with chronic neck pain, status‐post C5‐T1 spinal fusion who presented emergently with quadriparesis that following chiropractic neck manipulation. She felt a “pop” at the neck during the neck manipulation. She shortly thereafter began experiencing persistent neck pain associated with tingling sensations of both upper extremities on her drive home. She then noted transient right‐hand weakness as she was attempting to open a package. Her symptoms then temporarily resolved with rest, but after some time the paresthesia and neck pain reoccurred, worsened, and quickly progressed to quadriplegia. Brain MRI was negative for acute stroke. However, MRI of the cervical spine demonstrated acute cervical spinal cord ischemia in addition to post‐surgical changes. CTA head and neck reported normal arterial caliber. A diagnostic angiogram was performed that showed no evidence of arterial dissection but did demonstrate absence of the anterior spinal artery. Subsequently, CTA was further reviewed on thin slice revealing a “suboccipital rind sign" of the left V3 segment, suggesting left vertebral artery V3 segment dissection. Hypercoagulable workup was negative, and the patient was treated with anticoagulation. Conclusion Arterial dissection is usually readily diagnosable by CTA with high sensitivity. However, a study with normal caliber vessels in the reconstituted images does not always exclude an arterial dissection. To our knowledge there have been six reported vertebral dissection cases with a normal appearing lumen on CTA or conventional angiography. However, similar to our case, they displayed “suboccipital rind” signs on CTA thin cross‐section due to the thickening of the dissected artery on the V3 segment. The V3 segment has a horizontal course which runs parallel to the axially acquired imaging plane, which makes it difficult to appreciate the classic crescentic wall hematoma associated with arterial dissection. We hope that increased awareness of the typical location and appearance of the “suboccipital rind” sign on CTA may increase the detection rates of subtle arterial dissections in the setting normal‐appearing arterial lumens.

Influence of secondhand smoke exposure on the retinal vasculature of children in Hong Kong

BackgroundA recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children.MethodsThis is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables.ResultsHere we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001).ConclusionsExposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary.

Vascular Complications Following Transcatheter Aortic Valve Implantation, Using MANTA (Collagen Plug-Based) versus PROSTAR (Suture-Based), from a French Single-Center Retrospective Registry.

TAVI requires a large-bore arteriotomy. Closure is usually performed by the suture system. Some studies report a vascular complication rate of up to 21%. MANTA is a recently developed percutaneous closure system dedicated to large caliber vessels based on an anchoring system. Early studies report a lower rate of vascular complications with MANTA devices. This single-center retrospective study included all patients who underwent femoral TAVI at the Brest University Hospital from 20 November 2019 to 31 March 2021. The primary endpoint is the rate of vascular complications (major and minor) pre and post-TAVI procedure. In total, 264 patients were included. There were no significant differences in vascular complications (major and minor) between the two groups (13.6% in the MANTA group versus 21.2% in the PROSTAR group; p = 0.105), although there was a tendency to have fewer minor vascular complications in the Manta group (12.1% versus 20.5%; p = 0.067). Manta was associated with a lower rate of bleeding complications (3.8% versus 15.2%; p = 0.002), predominantly minor complications with fewer closure failures (4.5% versus 13.6%; p = 0.01), less use of covered stents (4.5% versus 12.9%; p = 0.016), and with no difference in the need for vascular surgery compared to the Prostar group (1.5% versus 2.3%; p = 0.652). On the other hand, Manta was associated with a higher rate of femoral stenosis (4.5% versus 0%; p = 0.013) without clinical significance (1.5% versus 0%; p = 0.156). The Manta and Prostar devices are equivalent in terms of vascular complications. The Manta, compared to the Prostar, is associated with fewer bleeding complications.

Intratesticular Vascular Architecture Seen by Ultrasound Microvascular Imaging (MicroV). Illustration of the Testis Vascular Anatomy.

The testis is a richly vascularized organ supplied by low-flow thin caliber vessels that are only partially detected by traditional Doppler systems, such as color and power Doppler. However, in the vascular representation, these techniques determine, albeit to different extents, a cut of the weak vessels due to the necessary application of wall filters that cut the disturbing frequencies responsible for artifacts generated by pulsations of the vascular walls and surrounding tissues. These filters cut a specific range of disturbing frequencies, regardless of whether they may be generated by low-flow vessels. Recently, a new technology, called Ultrasound Microvascular Imaging (MicroV) has been developed, which is particularly sensitive to slow flows. This new mode is based on new algorithms capable of better selecting the low frequencies according to the source of origin and cutting only the disturbing ones, saving the frequencies originating from really weak flows. When Ultrasound microvascular imaging is used, the vascular map is more detailed and composed of macro and microvasculature, with more subdivision branches, facilitating the interpretation of the normal and, consequently, the pathological. This review aims to describe the vascular architecture of the testis with Ultrasound Microvascular Imaging (MicroV) in healthy testis, compared to traditional color/power Doppler, related to normal anatomy.

Retinal main vessel calibers and systemic markers for long-term development of proliferative diabetic retinopathy.

To evaluate if retinal vascular calibers and systemic risk factors in patients with no or minimal diabetic retinopathy (DR) can predict risk of long-term progression to proliferative diabetic retinopathy (PDR). This was a matched case-control study of patients with diabetes having no or minimal DR at baseline with (cases) or without (controls) subsequent development of PDR. We collected six-field, 45-degree retinal images, demographic and clinical data from the Funen Diabetes Database. We included 52 eyes from 39 cases and 107 eyes from 89 controls matched on sex, age, type of diabetes, time from first to last screening episode and baseline DR level. Cases had higher HbA1c (73 vs. 55 mmoL/moL; p < 0.001), triglycerides (1.32 vs. 1.16 mmoL/L; p = 0.02) and longer duration of diabetes (19 vs. 14 years; p = 0.01), but the groups did not differ in calibers of retinal arterioles (229 vs. 227 μm; p = 0.49), venules (289 vs. 290 μm; p = 0.83) or the arterio-to-venule ratio (0.78 vs. 0.77; p = 0.86).In a multivariable logistic regression model with cluster robust standard error, HbA1c (OR 1.54 per 10 mmoL/moL; 95%-CI: 1.15-2.07; p = 0.004), triglyceride (OR 1.39 per 1 mmoL/L; 95%-CI: 1.03-1.86; p = 0.03) and duration of diabetes (OR 1.09 per year; 95%-CI: 1.03-1.16; p = 0.003) were independent risk factors for PDR. Retinal vascular calibers did not predict long-term development of PDR in contrast to well-established risk factors like HbA1c, triglyceride and duration of diabetes.

Pedunculagin and tellimagrandin-I stimulate inflammation and angiogenesis and upregulate vascular endothelial growth factor and tumor necrosis factor-alpha in vivo

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

Состояние сетчатки у пациентов, перенесших COVID-19 с поражением легких

Microvascular lesions are one of the main factors of lung and other organ damage in COVID-19. We hypothesized that patients with post-COVID lung dysfunction may also retain signs of systemic micro-vascular damage, in particular of the retina. Aim. To evaluate vascular and macular retinal area status in COVID-19 patients with pulmonary damage. Methods. 61 patient, average age 60.5 years, after in-patient COVID-19 treatment was examined. The volume of lung lesions according to high resolution computed tomography (HRCT) data ranged from 12 to 90 %. Decrease of diffusion capacity for carbon monoxide (DLCO) was observed in all patients after recovery: in 3 months in 18 patients (29.5 %) with severe COVID-19 DLCO was 58.4 % and in moderate COVID-19 – 73.2 % of the proper one. Optical coherence tomography (iVue-100, Optovue, USA) using Linear Scan and Nerve Fiber 3D Disc map was performed after 1 and 3 months. The control group included 20 patients comparable by sex, age, and comorbidity. Results. All patients showed typical signs of micro-circulatory disturbances in the posterior pole of the eye, increased caliber of arteries and first-order veins. In patients with severe COVID-19 an increase of arterial caliber by 22.5 μm and veins caliber by 35.04 μm, a decrease of retinal thickness in the macular region (by 8.78 μm in the fovea and by 6.6 μm in parafovea) compared to control group were revealed. After 6 months no significant dynamics of these parameters was revealed. Retinal changes in patients with moderate COVID-19 were similar but less pronounced. Conclusion.The revealed changes of retinal vessels and macular zone may indicate microcirculation disturbances and blood flow retardation in the posterior pole of the eye. The severity of the disturbances is comparable with the severity of the disease and the degree of DLCO reduction. Key words: COVID-19 with lung damage; retina; caliber of retinal vessels.

A deep learning system for retinal vessel calibre improves cardiovascular risk prediction in Asians with chronic kidney disease.

Cardiovascular disease (CVD) and mortality is elevated in chronic kidney disease (CKD). Retinal vessel calibre in retinal photographs is associated with cardiovascular risk and automated measurements may aid CVD risk prediction. Retrospective cohort study of 860 Chinese, Malay and Indian participants aged 40-80 years with CKD [estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2] who attended the baseline visit (2004-2011) of the Singapore Epidemiology of Eye Diseases Study. Retinal vessel calibre measurements were obtained by a deep learning system (DLS). Incident CVD [non-fatal acute myocardial infarction (MI) and stroke, and death due to MI, stroke and other CVD] in those who were free of CVD at baseline was ascertained until 31 December 2019. Risk factors (established, kidney, and retinal features) were examined using Cox proportional hazards regression models. Model performance was assessed for discrimination, fit, and net reclassification improvement (NRI). Incident CVD occurred in 289 (33.6%) over mean follow-up of 9.3 (4.3)years. After adjusting for established cardiovascular risk factors, eGFR [adjusted HR 0.98 (95% CI: 0.97-0.99)] and retinal arteriolar narrowing [adjusted HR 1.40 (95% CI: 1.17-1.68)], but not venular dilation, were independent predictors for CVD in CKD. The addition of eGFR and retinal features to established cardiovascular risk factors improved model discrimination with significantly better fit and better risk prediction according to the low (<15%), intermediate (15-29.9%), and high (30% or more) risk categories (NRI 5.8%), and with higher risk thresholds (NRI 12.7%). Retinal vessel calibre measurements by DLS were significantly associated with incident CVD independent of established CVD risk factors. Addition of kidney function and retinal vessel calibre parameters may improve CVD risk prediction among Asians with CKD.

Preoperative planning using virtual reality and computed tomography angiogram in deep inferior epigastric perforator flap breast reconstruction

The gold standard for preoperative planning of deep inferior epigastric perforator (DIEP) flap breast reconstruction uses computed tomography angiography (CTA). Virtual reality (VR) circumnavigates the limitations of CTA by reconstructing a fully immersive and interactive 3D representation of the scan. Scans of 44 patients who underwent DIEP flap breast reconstruction were retrospectively reviewed and compared using CTA and VR imaging modalities. The objective of this research was to compare perforators found using VR to the ones identified using conventional CTA. A correlation was found between the imaging modalities for unilateral (R = 0.96 (CI = 0.92, 0.98)) and bilateral (R = 0.93, (CI = 0.83, 0.97)) DIEP flap surgeries when comparing perforator location related to the umbilicus. Multivariable ordinal logistic regression found that higher intramuscular course length (IMC) is associated with the number of perforators found per side (OR = 1.79 (CI = 1.24, 2.6)), and medial location (OR = 2.85 (CI = 1.38, 5.87)). Larger vessel caliber (VC) is associated with shorter IMC (T2 vs. T3, OR = 3.34 (CI = 1.49, 7.49)), and branching in adipose tissue (AB) is associated with higher VC (T1 vs. T3, OR = 0.02 (CI = 0.007, 0.08); T2 vs. T3, OR = 0.24 (CI = 0.11, 0.55)). Overall, preoperative planning using VR was easy to use, safe, more intuitive, and provided in a time-efficient manner, more information about perforant characteristics. VR can improve the surgeon’s decision accuracy, relating to the best perforators for harvesting, in a shorter time period.

Effects of firsthand tobacco smoking on retinal vessel caliber: a systematic review and meta-analysis.

To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers. We performed a search on EMBASE and PubMed for studies up to 15th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed. Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases.

Comprehensive retinal vascular measurements: time in range is associated with peripheral retinal venular calibers in type 2 diabetes in China.

Retinal vascular parameters are biomarkers of diabetic microangiopathy. We aimed to investigate the relationship between time in range (TIR) assessed by continuous glucose monitoring (CGM) and retinal vascular parameters in patients with type 2 diabetes in China. The TIR assessed by CGM and retinal photographs were obtained at the same time from adults with type 2 diabetes who were recruited. Retinal vascular parameters were extracted from retinal photographs by a validated fully automated computer program, and TIR was defined as between 3.9-7.8mmol/L over a 24-h period. The association between TIR and caliber of retinal vessels distributed in different zones were analyzed using multivariable linear regression analyses. For retinal vascular parameters measurements, the peripheral arteriovenous and middle venular calibers widen with decreasing TIR quartiles (P < 0.05). Lower TIR was associated with wider peripheral venule after adjusting for potential confounders. Even after further correction for GV, there was still a significant correlation between TIR and peripheral vascular calibers (CV: β = - 0.015 [- 0.027, - 0.003], P = 0.013; MAGE: β = - 0.013 [- 0.025, - 0.001], P = 0.038) and SD: β = - 0.013 [- 0.026, - 0.001], P = 0.004). Similar findings were not found for the middle and central venular calibers or arterial calibers located in different zones. The TIR was associated with adverse changes to peripheral retinal venules but not central and middle vessels in patients with type 2 diabetes, suggesting that peripheral retinal vascular calibers may be affected by glycemic fluctuations earlier.

Food intake in South African children and retinal microvascular health: The ExAMIN Youth SA study

Background and aimsRetinal arteriolar narrowing and venular widening are associated with increased cardiovascular risk, even at young ages. Whether diet contributes to early microvascular changes in children is not widely explored. We explored the associations of frequency of healthy and unhealthy food group intake with retinal vessel calibers in black and white children. Methods and resultsThis study included school-aged (5–9 years) black (N = 433, 7.46 ± 0.98 years), and white (N = 403, 7.43 ± 0.82 years) children. Anthropometric and blood pressure measurements were taken, along with retinal vessel calibers (central retinal arteriolar (CRAE) and venular (CRVE) equivalents). Frequencies of food group intake were assessed using a food-frequency questionnaire. A factor analysis was performed to describe food group patters. Independent associations between retinal vessel calibers and frequencies of food group intake and food group patters were explored. In black children, cookies, cakes, and biscuits were associated with narrower arterioles (p < 0.05). In white children, cold sweetened beverages were associated with narrower arterioles (p = 0.02), whereas salty snacks were associated with narrower arterioles (p = 0.01) and wider venules (p < 0.05). Fruits were positively associated with CRAE (p = 0.03) in white children only. ConclusionA higher frequency of unhealthy food group consumption was associated with retinal arteriolar narrowing and venular widening in both black and white children. However, fruit intake was shown beneficial for retinal microvascular health in white children only. Our findings may highlight the importance of promoting healthy eating patterns from early childhood which may reduce the risk of premature cardiovascular disease development.

Conductivity reactivity index for monitoring of cerebrovascular autoregulation in early cerebral ischemic rabbits

BackgroundCerebrovascular autoregulation (CVAR) is the mechanism that maintains constant cerebral blood flow by adjusting the caliber of the cerebral vessels. It is important to have an effective, contactless way to monitor and assess CVAR in patients with ischemia.MethodsThe adjustment of cerebral blood flow leads to changes in the conductivity of the whole brain. Here, whole-brain conductivity measured by the magnetic induction phase shift method is a valuable alternative to cerebral blood volume for non-contact assessment of CVAR. Therefore, we proposed the correlation coefficient between spontaneous slow oscillations in arterial blood pressure and the corresponding magnetic induction phase shift as a novel index called the conductivity reactivity index (CRx). In comparison with the intracranial pressure reactivity index (PRx), the feasibility of the conductivity reactivity index to assess CVAR in the early phase of cerebral ischemia has been preliminarily confirmed in animal experiments.ResultsThere was a significant difference in the CRx between the cerebral ischemia group and the control group (p = 0.002). At the same time, there was a significant negative correlation between the CRx and the PRx (r = − 0.642, p = 0.002) after 40 min after ischemia. The Bland–Altman consistency analysis showed that the two indices were linearly related, with a minimal difference and high consistency in the early ischemic period. The sensitivity and specificity of CRx for cerebral ischemia identification were 75% and 20%, respectively, and the area under the ROC curve of CRx was 0.835 (SE = 0.084).ConclusionThe animal experimental results preliminarily demonstrated that the CRx can be used to monitor CVAR and identify CVAR injury in early ischemic conditions. The CRx has the potential to be used for contactless, global, bedside, and real-time assessment of CVAR of patients with ischemic stroke.

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex.

To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements. The between-device difference in CRAE (9.5 µm; 95% confidence interval, 8.0-11.1 µm) was larger than the between-device difference in CRVE (2.9 µm; 95% confidence interval, 1.3-4.5 µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4.8 to 23.9 µm for CRAE and -12.0 to 17.8 µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83-0.92) and 0.91 (95% confidence interval, 0.86-0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002). Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.

Impact of Lens Opacity on Optical Coherence Tomography Angiography Metrics

Purpose To evaluate the impact of lens opacity on the reliability of optical coherence tomography angiography metrics and to find a vessel caliber threshold that is reproducible in cataract patients. Methods A prospective cohort study of 31 patients, examining one eye per patient, by applying 3 × 3 mm macular optical coherence tomography angiography before (18.94 ± 12.22 days) and 3 months (111 ± 23.45 days) after uncomplicated cataract surgery. We extracted superficial (SVC) and deep vascular plexuses (DVC) for further analysis and evaluated changes in image contrast, vessel metrics (perfusion density, flow deficit and vessel-diameter index) and foveal avascular area (FAZ). Results After surgery, the blood flow signal in smaller capillaries was enhanced as image contrast improved. Signal strength correlated to average lens density defined by objective measurement in Scheimpflug images (Pearson’s r: –.40, p: .027) and to flow deficit (r= –.70, p < .001). Perfusion density correlated to the signal strength index (r = .70, p < .001). Vessel metrics and FAZ area, except for FAZ area in DVC, were significantly different after cataract surgery, but the mean change was approximately 3–6%. A stepwise approach in extracting vessels according to their pixel caliber showed a threshold of > 6 pixels caliber (∼20–30 µm) was comparable before and after lens removal. Conclusion In patients with cataract, OCTA vessel metrics should be interpreted with caution. In addition to signal strength, contrast and pixel properties can serve as supplementary quality metrics to improve the interpretation of OCTA metrics. Vessels with ∼20–30 µm in caliber seem to be reproducible.

Necrotizing plasma cell-rich aortitis and sudden cardiac death: Late sequelae of COVID-19?

The ongoing epidemic caused by the coronavirus SARS-CoV-2 is characterized by a variety of pathologic processes within the syndrome of COVID-19. Usually beginning as an upper respiratory infection with potential progression to a pneumonitis, many cases of COVID-19 that show minimal signs or symptoms initially may develop adverse systemic sequelae later, such as widespread thrombo-embolic phenomena, systemic inflammatory disorders (especially in children), or vasculitis. Here, we present a patient who suffered a sudden cardiac death following persistent SARS-CoV-2 viral positivity for four-and-one-half months after a mild clinical viral course. At routine autopsy, a remarkable plasma cell-rich necrotizing aortitis was uncovered. The aortic intima displayed diffuse, circumferential ongoing chronic intimal edema, inflammation, and neo-vascularization. The plasma cell-rich inflammatory process also involved the origin of the left main coronary artery (LM) causing a coronary arteritis accompanied by subacute, stenosing intimal vascular smooth muscle cell (VSMC) proliferation resulting in acute myocardial necrosis as a cause of death. A similar vasculitis and plaque were noted during the routine autopsy at the ostium of the celiac artery; vasculitis was not found systemically or in smaller caliber vessels. Through a variety of techniques including extensive histopathologic and immunohistochemical characterization, immunostaining localization of viral antigen, and transmission electron microscopy we present highly suggestive evidence that this unique necrotizing, plasma cell-rich aortitis is a rare sequela of COVID-19.

Repeatability and Comparability of Retinal Blood Vessel Caliber Measurements by OCTA.

To investigate the repeatability in vessel caliber measurements by optical coherence tomography angiography (OCTA). In this prospective study, 28 patients (47 eyes) underwent sequential OCTA imaging of the optic nerve head and macula. Two independent masked graders measured vessel caliber for sequential images of the optic nerve head and macula. The average vessel width was determined and variability between graders and images. A total of 8400 measurements of 420 vessels from 84 OCTA images were included in the analysis. Overall, inter-grader agreement was excellent (ICC 0.90). The coefficient of variation (CoV) for all repeated OCTA images was 0.10. Greater glaucoma severity, older age, macular location, and diagnosis of diabetes were associated with thinner vessels (p < 0.05). CoV was higher in the peripapillary region (0.07) as compared to the macula (0.15). ICC was high for all subgroups except for the macula (ICC = 0.72). Overall, the repeatability of vessel caliber measurements by OCTA was high and variability low. There was greater variability in the measurement of macular vessels, possibly due to technical limitations in acquiring accurate vessel widths for smaller macular vessels.

A dynamic multiscale model of cerebral blood flow and autoregulation in the microvasculature

Models of the micro-circulatory blood flow in the brain can play a key role in understanding the variety of cerebrovascular diseases that occur in the microvasculature. These conditions are often linked to structural modifications in the vessel network, alterations in the blood flow patterns, as well as impairment in the autoregulatory response, all of which are pathological changes that the model should be able to address if it were to have any clinical value. Furthermore, if the model results were to be validated against clinical MRI data, the model simulations need to be computationally feasible when used on networks on the scale of an MRI voxel. This requires some form of an upscaling approach that bypasses the need for an explicit architectural representation of the whole network while maintaining the relevant anatomical connections. To this end, we developed a hybrid multiscale model of blood flow and autoregulation that traces the dynamic changes in blood flow, volume, and pressure in the cortical microvasculature, where the discrete topology of the penetrating vessels is preserved, and these are then appropriately coupled to the homogenised capillary bed by a spatially distributing support function in the terminal endings. In contrast to the other multiscale models, the model developed here accounts for the dynamic physiological phenomena of the blood flow and the autoregulation processes in the microvessels. We show how the adaptive meshing scheme for the capillary bed developed in this study can be employed to ensure a scale-invariant coupling formulation and numerically accurate simulations, all without compromising the computational feasibility of the model. A statistically accurate cortical network on the scale of an MRI voxel is generated, and the model parameter values are calibrated using a Monte Carlo Filtering analysis to ensure that the model results are physiologically informed. The model is found to be able to capture the steep pressure gradients that have been reported to occur at coupling interfaces. Furthermore, in response to an upstream pressure drop, the network is found to be able to recover cerebral blood flow while exhibiting the characteristic autoregulatory behaviour in terms of changes in vessel calibre and the biphasic flow response. Overall, the model developed here offers a high-quality characterisation of dynamic flow and autoregulation in the microvasculature at improved computational efficiency and lays the ground for whole-brain dynamic simulations.

ANG2 Blockade Diminishes Proangiogenic Cerebrovascular Defects Associated With Models of Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder characterized by arteriovenous malformations and blood vessel enlargements. However, there are no effective drug therapies to combat arteriovenous malformation formation in patients with HHT. Here, we aimed to address whether elevated levels of ANG2 (angiopoietin-2) in the endothelium is a conserved feature in mouse models of the 3 major forms of HHT that could be neutralized to treat brain arteriovenous malformations and associated vascular defects. In addition, we sought to identify the angiogenic molecular signature linked to HHT. Cerebrovascular defects, including arteriovenous malformations and increased vessel calibers, were characterized in mouse models of the 3 common forms of HHT using transcriptomic and dye injection labeling methods. Comparative RNA sequencing analyses of isolated brain endothelial cells revealed a common, but unique proangiogenic transcriptional program associated with HHT. This included a consistent upregulation in cerebrovascular expression of ANG2 and downregulation of its receptor Tyr kinase with Ig and EGF homology domains (TIE2/TEK) in HHT mice compared with controls. Furthermore, in vitro experiments revealed TEK signaling activity was hampered in an HHT setting. Pharmacological blockade of ANG2 improved brain vascular pathologies in all HHT models, albeit to varying degrees. Transcriptomic profiling further indicated that ANG2 inhibition normalized the brain vasculature by impacting a subset of genes involved in angiogenesis and cell migration processes. Elevation of ANG2 in the brain vasculature is a shared trait among the mouse models of the common forms of HHT. Inhibition of ANG2 activity can significantly limit or prevent brain arteriovenous malformation formation and blood vessel enlargement in HHT mice. Thus, ANG2-targeted therapies may represent a compelling approach to treat arteriovenous malformations and vascular pathologies related to all forms of HHT.

The impact of in vitro embryo production on placental and umbilical cord vascularization is minimized by the addition of reproductive fluids

Animals born from in-vitro-produced (IVP) embryos show changes in the placenta and umbilical cord vascularization. This study compares the placental and umbilical vascular morphometry in pigs (n = 19) born through artificial insemination (AI group) or after transfer of IVP embryos cultured with (RF-IVP group) or without (C-IVP group) reproductive fluids. The relationship between vascular parameters and animal growth during the first year of life was also analyzed. Samples were collected at birth, fixed, paraffin-embedded, cut in sections, stained, and photographed for vascular and morphometric analysis with ImageJ® and Slide Viewer®. The average daily weight gain was individually scored from birth to the first year of life. No differences were found in placental vascular morphometry among groups, except for the vascular area of small vessels (arterioles, venules, and small vessels) that was higher in the C-IVP group. Regarding the umbilical cord, the values for perimeter (AI: 26.40 ± 3.93 mm; IVP: 30.51 ± 4.74 mm), diameter (AI: 8.35 ± 1.01 mm; IVP: 10.26 ± 1.85 mm), area (AI: 43.18 ± 12.87; IVP: 56.61 ± 14.89 mm2), and Wharton's jelly area (AI: 36.86 ± 12.04 mm2; IVP 48.88 ± 12.80 mm2) were higher in IVP-derived than AI-derived animals, whereas arterial and venous morphometric data were similar between groups. A correlation study showed that placental and umbilical cord vascular phenotypes affect the further growth of pigs. In conclusion, assisted reproductive technologies impact small caliber vessels in the placenta and morphometric parameters in the umbilical cord. The addition of reproductive fluids in IVP-embryo contributes to reduce the differences with in vivo-derived animals.