Changes In Vessels Research Articles

A semantic segmentation method to analyze retinal vascular parameters of diabetic nephropathy.

By using spectral domain optical coherence tomography (SD-OCT) to measure retinal blood vessels. The correlation between the changes of retinal vascular structure and the degree of diabetic nephropathy is analyzed with a full-pixel Semantic segmentation method. A total of 120 patients with diabetic nephropathy who were treated in the nephrology department of Quzhou People's Hospital from March 2023 to March 2024 were selected and divided into three groups according to the urinary albumin creatinine ratio (UACR). The groups included simple diabetes group (UACR < 30 mg/g), microalbuminuria group (30 mg/g ≤ UACR <300 mg/g) and macroalbuminuria group (UACR ≥300 mg/g). SD-OCT was used to scan the arteries and veins in the superior temporal area B of the retina. The semantic segmentation method built into the SD-eye software was used to automatically identify the morphology and structure of the vessels and calculate the parameters of arteriovenous vessels. The parameters of arteriovenous vessels are as follows: outer diameter of the retinal artery (RAOD); inner diameter of the retinal artery (RALD); arterial wall thickness (AWT); arterial wall to lumen ratio (AWLR); cross sectional area of arterial wall (AWCSA); retinal vein outer diameter (RVOD); retinal vein inner diameter (RVLD); vein wall thickness (VWT); vein wall to lumen ratio (VWLR); cross sectional area of vein wall (VWCSA). Statistical analysis software was used to compare and analyze the parameters of retinal arteriovenous vessels of the three groups. The study revealed statistically significant differences in RAOD and RALD among the three groups (p < 0.05) with the RAOD and RALD of the macroalbuminuria group and microalbuminuria group being lower than those of the simple diabetes group. Conversely, there were no significant differences in AWT, AWLR and AWCSA among the three groups (p > 0.05). Additionally, the differences in RVOD and RVLD among the three groups were found to be statistically significant (p < 0.05) with the RVOD and RVLD of the simple diabetes group being lower than those of the microalbuminuria group and macroalbuminuria group. No significant differences were observed in VWT and VWL among the groups. Additionally, RVOD and RVLD were weakly associated with UACR (R = 0.247, p = 0.007; R = 0.210, p = 0.021). Full-pixel semantic segmentation method combined with OCT images is a new retinal vascular scanning technology, which can be used as a new method for early diagnosis of diabetic nephropathy. The structural changes of retinal vessels can be used to predict the severity of diabetic nephropathy during the development of diabetic nephropathy.

Dynamic A-to-I RNA editing during acute neuroinflammation in sepsis-associated encephalopathy.

The activation of cerebral endothelial cells (CECs) has recently been reported to be the earliest acute neuroinflammation event in the CNS during sepsis-associated encephalopathy (SAE). Importantly, adenosine-to-inosine (A-to-I) RNA editing mediated by ADARs has been associated with SAE, yet its role in acute neuroinflammation in SAE remains unclear. Our current study systematically analyzed A-to-I RNA editing in cerebral vessels, cerebral endothelial cells (CECs), and microglia sampled during acute neuroinflammation after treatment in a lipopolysaccharide (LPS)-induced SAE mouse model. Our results showed dynamic A-to-I RNA editing activity changes in cerebral vessels during acute neuroinflammation. Differential A-to-I RNA editing (DRE) associated with acute neuroinflammation were identified in these tissue or cells, especially missense editing events such as S367G in antizyme inhibitor 1 (Azin1) and editing events in lincRNAs such as maternally expressed gene 3 (Meg3), AW112010, and macrophage M2 polarization regulator (Mm2pr). Importantly, geranylgeranyl diphosphate synthase 1 (Ggps1) and another three genes were differentially edited across cerebral vessels, CECs, and microglia. Notably, Spearman correlation analysis also revealed dramatic time-dependent DRE during acute neuroinflammation, especially in GTP cyclohydrolase1 (Gch1) and non-coding RNA activated by DNA damage (Norad), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs. The findings in our current study demonstrate substantial A-to-I RNA editing changes during acute neuroinflammation in SAE, underlining its potential role in the disease.

Age characteristics of myocardial blood supply in comorbid pathology

Understanding the age-related changes in myocardial blood supply under conditions of diabetes mellitus and stress will help reveal the pathway of diabetic cardiomyopathy, considering the age aspect. Therefore, the aim of our work is to investigate the age-related morpho-functional changes in the hemomicrocirculatory bed (HMB) of the myocardium in rats with experimental streptozotocin-induced diabetes mellitus (SDM) under conditions of chronic immobilization stress (CIS). The study used heart fragments and blood from 56 2-month-old and 6-month-old male white rats, which were divided into 3 groups: 1 group with comorbid pathology, including modeled SDM and CIS, 2 group with SDM, and 3 – control group. The material was collected 14th and 56th days from the start of the experiment. According to our findings, hyperglycemia, and stress on the 14th day of the experiment lead to spasm of the arterioles of the HMB and a significant deterioration in their permeability, as evidenced by a likely increase in the Vongenwort index in the arterioles. On the 56th days, in the experimental groups of 6-month-old rats, vacuolar dystrophy and coagulation necrosis of endotheliocytes and myocytes, focal destruction of capillary walls, thickening, and proliferation of their basement membrane, pronounced micro- and macroclasmatic changes, and capillarosclerosis are observed. In contrast, 2-month-old rats alongside destructive changes in HMB vessels show phenomena of neovascularization. Thus, SCD leads to the development of diabetic microangiopathy in the vessels of the myocardium of rats of different age groups. In animals with comorbid pathology, damage of HMB vessels are more pronounced on the 56th day of observation and is manifested by: destruction of capillary walls, capillarosclerosis. In 2-month-old rats, alongside destructively changed capillaries, we found to former new vessels with a characteristic ultrastructure. Keywords: heart, heart failure, diabetic cardiomyopathy, diabetes mellitus, cardiovascular diseases, hemomicrocirculatory bed.

The value of PMCTA in the diagnosis of coronary atherosclerosis in isolated human hearts.

The methods and parameters for coronary angiography in isolated human hearts were standardized based on the previous researcher.PMCTA in isolated human hearts is including the 3D reconstruction technique that reveals the coronary artery lesions more objectively and vividly, and provides the opportunity to re-read the data at anytime.PMCTA could only be used to examine the pathological changes of blood vessels, which might have limitations for the diagnosis of causes of death.PMCTA in isolated human hearts can be viewed as an auxiliary method for establishing the cause of death, which can provide an assessment of degree and extent of arterial stenosis and accurately help determine the abnormal location.

Duration of systemic alteration in vasomotor function of microvascular endothelium caused by the influenza A(H1N1)pdm09 virus

Introduction. The influenza A virus (IAV) can infect vascular endothelial cells and cause activation and/or dysfunction of the endothelium. Previously, we have shown that the influenza A(H1N1)pdm09 virus leads to alteration in functional activity of blood vessels in different vascular beds, and also causes various histopathological changes in pulmonary blood vessels of Wistar rats in the acute period of infection. Aim – to study the duration of systemic alteration in vasomotor function of microvascular endothelium caused by the influenza A(H1N1)pdm09 virus. Materials and methods. The Wistar rats were intranasally infected with the influenza A/St. Petersburg/48/16 (H1N1)pdm09 virus and at 1, 4, 7, 14, 21, 30, 60 and 90 days post infection (dpi) they were anesthetized and necropsied. The expression level of endothelial nitric oxide synthase (eNOS) was determined in mesenteric vascular endothelium by immunohistochemistry. The vasomotor activity of the mesenteric arteries was studied using wire myography. Results. The influenza A(H1N1)pdm09 virus causes a decrease in eNOS expression by 13–39 % within 60 dpi (p&lt;0.05). In addition, the influenza virus also reduces the maximal response of mesenteric arteries to the vasodilator by 74–108 % within 21 days (p&lt;0.0001) and reduces the response by 16–26 % within 30 and 60 dpi (p&lt;0.0001), respectively, and also increases the maximum response of the arteries to the vasoconstrictor by 26–57 % within 30 dpi (p&lt;0.05). It should be noted that such long-term changes are observed while virus is eliminated by the 7th dpi. Conclusion. The influenza A(H1N1) pdm09 virus causes long-term endothelial dysfunction in the Wistar rats which is characterized by the reduced expression of eNOS in mesenteric microvascular endothelium within 60 dpi, decrease of the maximal response of mesenteric microvessels to vasodilator within 60 dpi and increase of the maximal response to vasoconstrictor within 30 dpi. Alterations of systemic functional activity of mesenteric microvessels in rats infected with influenza A(H1N1)pdm09 virus are registered in absence of the reproduction of virus in mesenteric blood vessels while virus is eliminated from pulmonary tissues by the 7th dpi.

EVALUATION OF RISK FACTORS LEADING TO ROP IN SOUTHERN PUNJAB, A HOSPITAL BASED STUDY

The study aimed to assess the risk factors associated with retinopathy of prematurity (ROP) in premature children. The study was conducted prospectively in the Neonatal Unit of Nishtar Medical Hospital from January 2022 to December 2022 located in southern Punjab. The study included premature children who had a birth weight of less than 1500 g, gestational age of 32 weeks or less, and infants who had low Apgar scores, respiratory distress syndrome, blood transfusion, sepsis, infection, hydrocephaly, microcephaly, and twin pregnancy. Children with ischemic zones and changes in blood vessels had ROP and were treated by ophthalmologists and surgeons. The study found that out of the total 70 premature children included, 4 (5.7%) had active ROP, and 66 (94.2%) showed spontaneous regression of ROP. The patients with active ROP had a mean gestational age of 27.4±1.4 weeks, and there was a significant association between early gestational age and ROP. Patients who developed active ROP had oxygen therapy for 21±3.5 days compared to 12.6±1.2 days in those without ROP (P&lt;0.05). The most common retinal changes were the development of ischemic zones (61.4%), bleeding (24.2%), changes in blood vessels (15.7%), and changes in the optic nerve (1.4%). Of the 70 patients, 4 (5.7%) were in Zone I, 21 (30%) were in Zone II, and 45 (64.2%) were in Zone III. All patients in the zone I had active ROP, suggesting a significant association between zones and the development of ROP (P &lt;.05). In conclusion, the study found that low birth weight, early gestational age, low Apgar score, and longer duration of oxygen therapy significantly increased the risk of ROP.

Dynamic Computed Tomography Angiography for capturing vessel wall motion: A phantom study for optimal image reconstruction.

Reliably capturing sub-millimeter vessel wall motion over time, using dynamic Computed Tomography Angiography (4D CTA), might provide insight in biomechanical properties of these vessels. This may improve diagnosis, prognosis, and treatment decision making in vascular pathologies. The aim of this study is to determine the most suitable image reconstruction method for 4D CTA to accurately assess harmonic diameter changes of vessels. An elastic tube (inner diameter 6 mm, wall thickness 2 mm) was exposed to sinusoidal pressure waves with a frequency of 70 beats-per-minute. Five flow amplitudes were set, resulting in increasing sinusoidal diameter changes of the elastic tube, measured during three simulated pulsation cycles, using ECG-gated 4D CTA on a 320-detector row CT system. Tomographic images were reconstructed using one of the following three reconstruction methods: hybrid iterative (Hybrid-IR), model-based iterative (MBIR) and deep-learning based (DLR) reconstruction. The three reconstruction methods where based on 180 degrees (half reconstruction mode) and 360 degrees (full reconstruction mode) raw data. The diameter change, captured by 4D CTA, was computed based on image registration. As a reference metric for diameter change measurement, a 9 MHz linear ultrasound transducer was used. The sum of relative absolute differences (SRAD) between the ultrasound and 4D CTA measurements was calculated for each reconstruction method. The standard deviation was computed across the three pulsation cycles. MBIR and DLR resulted in a decreased SRAD and standard deviation compared to Hybrid-IR. Full reconstruction mode resulted in a decreased SRAD and standard deviations, compared to half reconstruction mode. 4D CTA can capture a diameter change pattern comparable to the pattern captured by US. DLR and MBIR algorithms show more accurate results than Hybrid-IR. Reconstruction with DLR is >3 times faster, compared to reconstruction with MBIR. Full reconstruction mode is more accurate than half reconstruction mode.

Morphological changes of the hepatobiliary system and salivary glands under the influence of stress

Stress can impact our bodies at the cellular level, causing changes to various organs and systems. Chronic stress can indirectly affect the hepatobiliary tract. Salivary gland dysfunction can be a manifestation of a large variety of systemic diseases or the consequence of local structural or functional pathologies. Stress can influence the oral microbiome, leading to changes in microbial diversity. Scientists study stress reactions, new resistance methods, and modern approaches to prevent and treat stress. &#x0D; The aim is to examine the morphological aspects and changes of the blood vessels in the liver and salivary glands of white rats in experiment using acute immobilization stress.&#x0D; Materials and methods. In total 22 white male rats were studied, divided into two groups. The first was kept as a control, the second was subjected to acute immobilization stress. The rats were immobilized by hanging them by the neck with a clamp for 6 hours. Animals were euthanized with a sodium thiopental solution. Samples of the liver and parotid gland were examined histologically using hematoxylin and eosin stain.&#x0D; Results. The livers of rats were studied after acute immobilization stress. Significant changes were observed in the liver blood vessels, including thrombosis and expansion of perisinusoidal spaces. Liver cells also showed changes such as karyopyknosis, colliquation necrosis, and hydropic dystrophy. The parotid salivary gland histologic examination showed swelling in the connective tissue, periductal regions, and perivascular spaces. In the acinar section, basophilia and swelling of serocytes were observed, along with dystrophic processes leading to remodeling of the acini and ducts. The narrowing of arterioles was observed, reflecting tension in the arterial system.&#x0D; Conclusions. Exposure to acute stress can cause changes in the liver and biliary tract, increasing the risk of various diseases, including those that affect the oral cavity.

Natural Fatty Acid Guards against Brain Endothelial Cell Death and Microvascular Pathology following Ischemic Insult in the Presence of Acute Hyperglycemia.

Ischemic stroke is worsened by the presence of sudden high blood sugar levels, even in individuals without pre-existing diabetes. This elevated glucose concentration hampers the ability of energy-starved brain cells to efficiently use it as a source of energy. Consequently, this leads to the production of abundant amounts of toxic glucose metabolites, which trigger oxidative stress in the brain milieu, particularly in the microvasculature of the brain. A prominent feature of this oxidative stress is the demise of endothelial cells, causing detrimental changes in blood vessels, including a reduction in their vascular diameter, a decreased efficiency of vessel proliferation, and the impaired integrity of tight junctions. These vascular pathologies contributed to an increase in the volume of damaged tissues (infarct), an exacerbation of brain swelling (edema), and a decline in cognitive and motor functions. In a mouse model of ischemic stroke with induced acute hyperglycemia, a naturally occurring saturated fatty acid provides protective cover to the microvasculature by preventing damage related to oxidative stress. Our current research revealed that lauric acid (LA) attenuated infarct volume and reduced brain edema by reducing endothelial cell death, enhancing vessels' diameter, promoting vascular angiogenesis, and stabilizing barrier functions. Animals administered with this natural compound showed a significant reduction in 4-HNE-positive vessels. In conclusion, natural saturated fatty acids help to preserve brain microvascular functions following ischemic insults in the presence of acute hyperglycemia.

Experimental study of the depressurization phenomena of supercritical carbon dioxide system

Depressurization accidents pose a significant safety concern for supercritical carbon dioxide (S–CO2) nuclear and power systems. However, due to the limited availability of system-level experiments, clear understandings of the phenomena associated with S–CO2 depressurization accidents are lacking. To address this gap, this paper conducted a series of experiments on a S–CO2 system to investigate the characteristics of depressurization accidents. Several key phenomena, including flash evaporation, transcritical transient heat transfer, fluid-thermo-structure coupling effect, and the fluid field changes in containment vessel, were identified and analyzed. Furthermore, the impact of break size and location, containment vessel, and initial system conditions on depressurization accidents was investigated. The acquired results provide crucial groundwork for establishing a Phenomenon Identification Ranking Table (PIRT) tailored to depressurization accidents in S–CO2 nuclear and power systems. This will significantly enhance the design and safety analysis of these systems.

Burden of cerebral small vessel disease and changes of diastolic blood pressure affect clinical outcome after acute ischemic stroke

Elevated and low blood pressure (BP) may lead to poor functional outcome after ischemic stroke, which is conflicting. Hence, there must be another factor—such as cerebral small vessel disease (cSVD) -interacting with BP and thus, affecting outcome. Here, we investigate the relationship between BP and cSVD regarding outcome after stroke. Data of 423/503 stroke patients were prospectively analyzed. Diastolic (DBP) and systolic BP (SBP) were collected on hospital admission (BPad) and over the first 72 h (BP72h). cSVD-burden was determined on MR-scans. Good functional outcome was defined as a modified Rankin Scale score ≤ 2 at hospital discharge and 12 months thereafter. cSVD was a predictor of poor outcome (OR 2.8; p < 0.001). SBPad, DBPad and SBP72h were not significantly associated with outcome at any time. A significant relationship was found between DBP72h, (p < 0.01), cSVD (p = 0.013) and outcome at discharge. At 12 months, we found a relationship between outcome and DBP72h (p = 0.018) and a statistical tendency regarding cSVD (p = 0.08). Changes in DBP72h were significantly related with outcome. There was a U-shaped relationship between DBP72h and outcome at discharge. Our results suggest an individualized stroke care by either lowering or elevating DBP depending on cSVD-burden in order to influence functional outcome.

Combination of intraoperative indocyanine green video-angiography FLOW 800 and computed tomography perfusion to assess the risk of cerebral hyperperfusion syndrome in chronic internal carotid artery occlusion patients after revascularization surgery.

To study the changes of corticocerebral hemodynamics in surgical area and postoperative hyperperfusion syndrome in patients with chronic internal carotid artery occlusion (CICAO) by intraoperative indocyanine green videoangiography (ICGA)-FLOW 800 and CT perfusion after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery. From October 2019 to January 2021, 77 patients diagnosed with CICAO underwent direct bypass surgery at Huadong hospital (affiliated with Fudan University) were enrolled. Regions of interest (ROIs) at STA, proximal MCA (PMCA), distal MCA (DMCA), cortical blood capillary (CBC), and cortical vein (CV) were identified after anastomosis by ICGV-FLOW 800 including peak fluorescence intensity (PFI), time to peak (TTP), and area under the time curve (AUC) of fluorescence intensity. All patients underwent perfusion-weighted CT before bypass surgery and those patients with HPS were verified by CTP after bypass. 14 patients with HPS were verified by perfusion-weighted CT after bypass. In HPS group, the AUCTTP of DMCA was significantly larger (T = -3.301, p = 0.004) and TTP of CBC was shorter (T = -2.929, p = 0.005) than patients in non-HPS group. The larger AUCTTP of DMCA (OR = 3.024, 95%CI 1.390-6.578, p = 0.0050) was an independent risk factor by further multivariate logistic regression analysis. The hemodynamic changes of cortical vessels during STA-MCA bypass surgery could be recorded accurately by ICGV-FLOW 800. Furthermore, the increased AUCTTP of DMCA and shorter TTP of CBC may be potential risk factors of HPS.

Pathomorphology of the heart in COVID-19

Cardiovascular system is a significant target for SARS-CoV-2.The objective was to study morphological changes in the heart in patients who died from COVID-19.Materials and methods. Autopsy material of the heart of those who died from COVID-19 (700 autopsies) was analyzed. The analysis of autopsy protocols was carried out, macroscopic changes were assessed, histological preparations stained with hematoxylin and eosin, van Gieson stain, Schiff’s reagent, the results of immunohistochemistry with antibodies to CD68, CD3, CD4, CD8, CD45 were analyzed.Results. The leading pathomorphological changes in the heart in COVID-19 are acute discirculatory changes with predominant disorders in small intramyocardial vessels. Lymphocytic myocarditis was confirmed in 1 % of cases.Conclusion. Damage to cardiomyocytes in COVID-19 is multifactorial and associated with manifestations of the underlying cardiovascular pathology, changes in intramyocardial vessels due to the action of SARS-CoV-2, and hypoxia due to progressive lung damage.

Cerebrovascular Changes in Dementia Patients with Alzheimer’s Disease and Vascular Parkinsonism

AbstractBackgroundWhen examining patients with dementia, it is necessary to clearly differentiate the developed cerebrovascular and microcirculatory changes. We present the features of cerebral angioarchitectonics and microcirculation in Alzheimer’s disease (AD) and vascular parkinsonism (VP).MethodsThe research included 155 patients. The examination included assessment of CDR, TDR, MMSE, cerebral MRI, CT, scintigraphy (SG), rheoencephalography (REG), cerebral multi‐gated angiography (MUGA).Patients were divided into:• 93 people aged 34‐80 (mean age 67.5): men ‐ 32 (34.40%), women ‐ 61 (65.59%), suffering from AD. According to dementia severity, patients were subdivided: (TDR‐0) ‐ 10, (TDR‐1) ‐ 29, (TDR‐2) ‐ 36, (TDR‐3) ‐ 18 people;• 62 people aged 52‐80 (mean age 77): men ‐ 48 (77.42%), women ‐ 14 (22.58%), suffering from VP. According to dementia severity, patients were subdivided: no dementia ‐ 30 people, dementia at level (CDR‐1) ‐ 32 people.ResultsIn AD patients, changes in angioarchitectonics and microcirculation are manifested in:• Absence of calcium salts deposits and atherosclerotic changes in intracerebral vessels;• Increased tortuosity of distal intracranial arteries;• Reduction of the capillary bed in the temporal and frontoparietal regions;• Development of multiple, large arteriovenous shunts with early venous discharge of arterial blood in the same regions;• Development of abnormal, intracerebral venous trunks;• Development of intracerebral stagnation of venous blood.These changes are called “Discirculatory angiopathy of Alzheimer’s type” (DAAT).In patients with VP, changes in angioarchitectonics and microcirculation are manifested in:• Multiple calcium salts deposits with atherosclerotic changes in intracranial vessels, mainly in the thalamus, basal ganglia, and pons;• Local decrease in subcortical cerebral capillary blood flow in the same regions;• Development of local subcortical small intracerebral arteriovenous shunts;• Absence of expressed intracerebral venous blood stagnation.ConclusionsDiscirculatory angiopathy of Alzheimer’s type (DAAT), regardless of dementia severity, is an AD‐specific cerebrovascular and microcirculatory lesion of the brain, unconnected with atherosclerotic process.In patients with VP, regardless of dementia, vascular and microcirculatory changes are atherosclerotic in nature. Capillary bed lesions, presence of arteriovenous shunts are subcortical in nature, mainly in the region of the thalamus, basal ganglia, and bridge. Marked venous stasis does not occur in this case.

Age‐ and Sex‐Related Morphological Changes in Cerebral Blood Vessels: a 7T TOF MRA Study

AbstractBackgroundIn this study we evaluated age‐ and sex‐associated morphological changes of cerebral blood vessels using 7T Time‐of‐flight (TOF) magnetic resonance angiography (MRA).MethodOur study consisted of 25 cognitively normal older adults (20 female, mean age 68.2 years). Whole‐Brain TOF MRA images were collected on a 7T Siemens scanner at the University of Pittsburgh (slice number = 354, voxel size = 0.38*0.38*0.38 mm, 12 mins). An iterative vessel segmentation algorithm, VesselMapper, was used to segment blood vessels on TOF MRA images (Li et al., 2023). For each subject, vessels are further divided into large and small vessels by median split based on vessel diameters. Mean tortuosity of large vessels, small vessels and overall vessels was computed. Linear regression analyses were performed to evaluate the main effects of age and sex, and the age*sex interaction on vessel tortuosity and diameter.ResultAs shown in Figure 1, we found age‐related increase in mean vessel tortuosity (greater age is associated with greater tortuosity, p&lt;0.02). This age‐related difference is driven by small vessels (p = 0.002) rather than large vessels (p = 0.7). We also found that age is positively associated with mean voxel tortuosity (p&lt;0.001, black line in Figure 2). Furthermore, women showed greater age‐related increase in mean arterial tortuosity, compared to men (age*sex interaction p = 0.04, Figure 2).ConclusionOur findings validated that morphological markers of cerebral blood vessels are sensitive to aging. Small vessels in the brain are particularly vulnerable. Further, compared to men, older women are at a higher risk for cerebral small vessel disease, which may contribute to elevated SVD‐related AD risk in women.Limitation: The study has an unbalanced sample (more women than men) and a relatively modest sample size (N = 25). A cross‐sectional instead of longitudinal design was used in this analysis. Future study with a large balanced sample and a longitudinal design are required to confirm our findings.Reference: Li, Jiatai, et al. “VesselMapper ‐ A Robust Vessel Segmentation Algorithm for 3D Images.” Annual Meeting of the Organization for Human Brain Mapping. 2023

Age‐ and Sex‐Related Morphological Changes in Cerebral Blood Vessels: a 7T TOF MRA Study

AbstractBackgroundIn this study we evaluated age‐ and sex‐associated morphological changes of cerebral blood vessels using 7T Time‐of‐flight (TOF) magnetic resonance angiography (MRA).MethodOur study consisted of 25 cognitively normal older adults (20 female, mean age 68.2 years). Whole‐Brain TOF MRA images were collected on a 7T Siemens scanner at the University of Pittsburgh (slice number = 354, voxel size = 0.38*0.38*0.38 mm, 12 mins). An iterative vessel segmentation algorithm, VesselMapper, was used to segment blood vessels on TOF MRA images (Li et al., 2023). For each subject, vessels are further divided into large and small vessels by median split based on vessel diameters. Mean tortuosity of large vessels, small vessels and overall vessels was computed. Linear regression analyses were performed to evaluate the main effects of age and sex, and the age*sex interaction on vessel tortuosity and diameter.ResultAs shown in Figure 1, we found age‐related increase in mean vessel tortuosity (greater age is associated with greater tortuosity, p&lt;0.02). This age‐related difference is driven by small vessels (p = 0.002) rather than large vessels (p = 0.7). We also found that age is positively associated with mean voxel tortuosity (p&lt;0.001, black line in Figure 2). Furthermore, women showed greater age‐related increase in mean arterial tortuosity, compared to men (age*sex interaction p = 0.04, Figure 2).ConclusionOur findings validated that morphological markers of cerebral blood vessels are sensitive to aging. Small vessels in the brain are particularly vulnerable. Further, compared to men, older women are at a higher risk for cerebral small vessel disease, which may contribute to elevated SVD‐related AD risk in women. Limitation: The study has an unbalanced sample (more women than men) and a relatively modest sample size (N = 25). A cross‐sectional instead of longitudinal design was used in this analysis. Future study with a large balanced sample and a longitudinal design are required to confirm our findings. Reference: Li, Jiatai, et al. “VesselMapper ‐ A Robust Vessel Segmentation Algorithm for 3D Images.” Annual Meeting of the Organization for Human Brain Mapping. 2023

Correlation between Carotid Blood Flow Velocity and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients with Recent Small Subcortical Infarcts.

The common and internal carotid arteries are the upstream vessels of the small cerebral vessels. The relationship between hemodynamic changes in the significant cervical vessels and cerebral small vessel disease (CSVD) remains uncertain. This research sought to analyze the correlation between carotid blood flow velocity and the total magnetic resonance imaging (MRI) burden of CSVD in patients with recent small subcortical infarcts (RSSIs). Data were gathered from individuals diagnosed with RSSIs admitted to Changzhou Second People's Hospital between January 2022 and June 2023. Brain MRI was performed on every patient to determine the overall MRI burden of CSVD, along with carotid duplex ultrasound to evaluate carotid blood flow velocity and pulsatility index (PI) of the common carotid (CCA) and internal carotid (ICA) arteries. The association between carotid blood flow velocity and the total MRI load of CSVD was examined using univariate and multivariate analyses. For our investigation, 272 individuals with RSSIs were screened. 82 individuals had a moderate to severe load of CSVD, while 190 participants showed a mild burden. Patients with moderate to severe burden of CSVD had lower end-diastolic velocity (EDV) and higher PI in CCA and ICA than those with mild load (P < 0.001). After adjusting for variables like age, hypertension, systolic blood pressure, and blood homocysteine levels, multivariate logistic regression analysis showed that EDV in CCA (OR, 0.894; P = 0.011), PI in CCA (OR, 5.869; P = 0.017), EDV in ICA (OR, 0.909; P = 0.008), and PI in ICA (OR, 5.324; P = 0.041) were independently related to moderate to severe CSVD burden. Spearman correlation analysis showed that EDV in CCA and ICA was negatively related to the total MRI load of CSVD in patients with RSSIs (P < 0.001). PI in CCA and ICA was positively associated with the whole MRI load of CSVD (P < 0.001). Low carotid blood flow velocity and high carotid pulsatility index are independently associated with moderate to severe burden of CSVD.

The Role of P-Selectin in Microvascular Hemodynamics and Cerebral Brain Volumes in Aging Sickle Cell Mice

Cerebral vasculopathy has been linked to the development of cognitive impairment in sickle cell disease (SCD). We have previously demonstrated that 13-month-old sickle cell mice recapitulate features of cerebral vasculopathy such as tortuous vessels, microthrombi, and hypoperfusion seen in adults with SCD. Histologically, we also showed these mice have increased cerebral microvascular deposition of P-selectin and more frequent and larger microinfarcts compared to matched controls. We further showed that these mice developed evidence of cognitive deficit compared to matched controls. Based on these observations, we hypothesized P-selectin may play a critical role in development of cerebral micro vasculopathy and downstream pathologic sequalae such as microinfarcts by enhancing leukocyte-endothelial interactions. Furthermore, abundant evidence from non-sickle mice shows that microinfarcts can exacerbate small vessel changes including gray matter volume loss. Building on our prior work, in this study, we examined the effect of P-selectin deficiency on cerebral microvascular hemodynamics and leukocyte-endothelial interaction and well as changes in cortical and subcortical gray matter volume in aged sickle mice. Male, P-selectin knockout (Psel KO) or intact (Psel WT) chimeric mice were generated by transplanting control (AA) or sickle (SS) bone marrow into P-selectin knockout (Psel -/-) or C57BL/6 (B6) recipients. To assess the impact of vasculopathy and brain gray matter volume changes longitudinally, male mice were assessed at 12-, 14- or 16-month post-transplant. Hemodynamics (mean velocity, red blood cell (RBC) flux, white blood cell stalls in capillaries as well as venules) were obtained from line-scan images acquired using in-vivo two-photon microscopy, using custom and validated MATLAB scripts. Gray matter volumes in 26 cortical and subcortical brain regions with relevance to cognitive function, were derived from parcellation of T2-weighted magnetic resonance imaging after non-linear registration to Allen brain atlas T1 anatomical space. Parcellation was accomplished by registering the Paxinos atlas to the mouse T2 now in Allen space. Brain volume analyses was accomplished using Analyze 12 software. After the completion of in-vivo studies, brains were extracted for immunohistochemistry analysis. Statistical analysis was performed using two-way ANOVA. The breakdown of the mice included in this study are; 14 B6 AA, 12 B6 SS, 12 Psel KO AA and 13 Psel KO SS. Given the high attrition rate in older mice, data from 12-, 14- and 16-month-old cohorts were combined. Mean age of B6 AA cohort was 13.1 months, 12.8 months for B6 SS, 13. 9 months for Psel KO AA and 13.6 months for Psel KO SS mice and were not statistically different. Psel KO sickle mice had a significantly lower mean capillary RBC velocity (1.733 mm/s vs 4.717 mm/s, p &amp;lt; 0.01) compared to Psel WT SS mice. In addition, Psel KO SS mice had relatively smaller (more normal) capillary diameter compared to Psel WT SS mice (6.248 um vs 8.613 um, p &amp;lt; 0.001). Interestingly, there was no statistically significant difference in RBC flux between Psel KO SS and Psel WT SS mice, however Psel KO SS mice show a lower red blood cell flux similar to that seen in Psel WT AA mice ( Figure 1). Of the 26 brain regions that were assessed, Psel KO SS mice had larger measured gray matter volume in the frontal association cortex (3.01 ± 0.77 vs 3.66± 0.33 mm 3, p= 0.0083), prelimbic cortex (1.72 ± 0.27 vs 1.95 ± 0.17 mm 3, p=0.0079), hippocampus (17.67 ± 1.56 vs 16.21± 1.97 mm 3, p=0.01)( Figure 1) including other regions such as lateral (2.12 ± 0.19 vs 1.88 ± 0.31 vs mm 3 p=0.0096) medial (1.84± 0.16 vs 1.64 ± 0.26 mm 3, p=0.01), and ventral orbital cortex( 1.95± 0.17 vs1.72 ± 0.27 mm 3, p=0.01) and dorsolateral olfactory tract (1.46 6± 0.13 vs 1.31 ± 0.20 mm 3, p=0.023 compared to the Psel WT SS mice (data not shown). In conclusion, non-hematopoetic P-selectin deficiency improves cerebral vasculopathy as demonstrated by normalization of hemodynamics in sickle mice. We also show that Psel KO SS mice had larger brain gray matter volume in regions involved in cognitive function. Additional studies are needed to identify the underlying mechanism of improvement in brain gray matter volume as well as whether P-selectin could be potential target for reducing SCD associated neurological complications.

Age-induced aortic modifications are accompanied by alterations in the antioxidant defense system in female rats

IntroductionAging leads to significant structural and functional changes in blood vessels, which disrupt their normal function and impact cardiovascular health. Current research is actively exploring the NRF2 antioxidative pathway, recognizing its role in protecting cells by preserving their antioxidant defenses against damage. However, there has been limited exploration into the role of the NRF2 pathway in vascular aging. The primary objective of this study was to determine whether age-related changes in the aorta are associated with variations in the baseline levels of antioxidant enzymes, with a particular emphasis on how the NRF2 pathway operates in the aortic wall.MethodsA group of healthy aging female SD rats was compared with their younger counterparts. Various assessments were conducted, including measuring blood pressure, analyzing serum lipid profiles, examining aortic tissue, and assessing the expression of antioxidant enzymes.ResultsThe results revealed significant differences in both blood pressure and serum lipid levels between the aged and younger rats. The examination of the aorta in older rats showed structural alterations, increased apoptosis, and the accumulation of fatty deposits. In the older rats, levels of SOD-1 (superoxide dismutase) and GSS (glutathione synthetase) were lower, whereas NRF2, KEAP-1 (Kelch-like ECH-associated protein 1), and HO-1 (Heme oxygenase 1) were higher.DiscussionThis study advances our understanding of how aging affects the antioxidant system in blood vessels, particularly in relation to the regulation of the NRF2/HO-1 pathway in the aorta. These findings suggest that targeting the NRF2/HO-1 pathway could present anovel therapeutic approach for addressing age-related vascular issues.

Choroidal Vessel and Stromal Volumetric Analysis After Photodynamic Therapy or Focal Laser for Central Serous Chorioretinopathy.

To utilize volumetric analysis to quantify volumetric changes in choroidal vessels and stroma after photodynamic therapy (PDT) and focal laser photocoagulation (PC) for central serous chorioretinopathy (CSCR). This retrospective, comparative study included 58 eyes (58 patients) with CSCR (PC, 33 eyes; PDT, 25 eyes) followed up with swept-source optical coherence tomography at 3 months after treatment. Three-dimensional (3D) choroidal vessel and stromal volumes in each area of the central 1.5-mm-diameter circle, the torus-shaped area with 6-mm-diameter circle excluding the area of the central 1.5-mm-diameter circle, and the treated area of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid centered at the fovea were analyzed using a deep learning-based method. Changes in volume at baseline and 1 and 3 months after treatment were compared. The mean patient age was 49.3 ± 10.5 years. In the central 1.5-mm-diameter circle, the mean vessel and stromal volume rates significantly decreased after the treatment in both the PDT and PC groups (P = 0.00029 and P = 0.0014, respectively), and significant differences between the PDT and PC groups of continuous variables within times were observed in both volumes (P = 0.024 and P = 0.037, respectively). In the torus-shaped area and treated area, the PDT and PC groups both showed similar decreases in vessel and stromal volume over time. In the 3D optical coherence tomography volumetric analysis, both PDT and focal PC reduced choroid vessel volume in eyes with CSCR. This new finding is useful in elucidating the pathogenesis and healing mechanisms of CSCR.