Vascular Caliber Research Articles

Characterizing Vascular Wall and Lumen Caliber in Eyes with Diabetic Retinopathy Based on Adaptive Optics Scanning Laser Ophthalmoscopy.

Each study eye underwent mydriasis and AOSLO imaging in a single-visit study. The instrument's arrangement of four offset aperture images provided two orthogonal split-detector images and enabled isotropic analysis of the arteriolar boundaries. For each arteriole, we calculated the wall-to-lumen ratio (WLR), mean wall thickness, and luminal and external diameters. In total, we enrolled 5 (20.8%) healthy control eyes and 19 eyes of patients with T1D. The DR distribution was: four (16.7%) no-DR, nine (37.5%%) mild or moderate nonproliferative DR (NPDR), and six (25%) severe NPDR or proliferative DR. Mean wall thickness increased significantly in eyes with T1D compared to healthy controls (p = 0.0006) and in eyes with more advanced DR (p = 0.0004). The WLR was significantly higher in eyes with T1D (p = 0.002) or more severe DR (p = 0.004). There was no significant relationship between T1D status or DR severity and any of the arteriolar diameters. In this preliminary study, there appeared to be increases in the WLR and mean wall thickness in eyes with T1D and more severe DR than in the controls and eyes with no/less severe DR. Future studies may further elucidate the relationship between the retinal arteriolar structure and physiologic alterations in DR.

Obstructive sleep apnea and cerebral small vessel disease in community-based older people: an aspirin in reducing events in the elderly imaging substudy

Abstract Study Objectives Obstructive sleep apnea (OSA) may increase the risk of dementia. A potential pathway for this risk is through cerebral small vessel disease (CSVD). In the context of an existing randomized trial of aspirin for primary prevention, we aimed to investigate OSA’s impact on CSVD imaging measures and explore whether aspirin effects these measures over 3 years that differ in the presence or absence of OSA. Methods A substudy of the aspirin in reducing events in the elderly (ASPREE) randomized placebo-controlled trial of low-dose aspirin. Community-dwelling participants aged 70 years and above, without cognitive impairment, cardiovascular disease, or known OSA completed an unattended limited-channel sleep study that calculated the oxygen desaturation index and apnea–hypopnea index. At baseline and 3 years later, volumes of white matter hyperintensities (WMH) and silent brain infarctions (SBI) were measured on 1.5 Tesla brain magnetic resonance imaging, and retinal vessel calibers were calculated from retinal vascular imaging. Results Mild and moderate/severe OSA was detected in 48.9% and 29.9%, respectively, of the 311 participants, who had a mean age of 73.7 years (SD 3.4 years), 38.6% female. OSA of any severity was not associated with WMH volumes, SBI, nor retinal vessel calibers at baseline, nor with change in these measures in the 277 participants with repeated measures acquired after 3 years. OSA of any severity did not interact with aspirin on change in these measures over 3 years. Conclusions In healthy older adults undiagnosed OSA was not associated with retinal vascular calibers and neuroimaging measures of CSVD. Clinical Trial Information ASPREE trial has registration with the International Standard Randomized Controlled Trial Number (ISRCTN) www.isrctn.com, ISRCTN83772183 and with www.clinicaltrials.gov, NCT01038583. SNORE-ASA has registration with the Australian New Zealand Clinical Trials Registry (ANZCTR) at www.anzctr.org.au, ACTRN12612000891820.

Whole-Brain Vascular Architecture Mapping Identifies Region-Specific Microvascular Profiles In Vivo.

The novel MR imaging technique of vascular architecture mapping allows in vivo characterization of local changes in cerebral microvasculature, but reference ranges for vascular architecture mapping parameters in healthy brain tissue are lacking, limiting its potential applicability as an MR imaging biomarker in clinical practice. We conducted whole-brain vascular architecture mapping in a large cohort to establish vascular architecture mapping parameter references ranges and identify region-specific cortical and subcortical microvascular profiles. This was a single-center examination of adult patients with unifocal, stable low-grade gliomas with multiband spin- and gradient-echo EPI sequence at 3T using parallel imaging. Voxelwise plotting of resulting values for gradient-echo (R2*) versus spin-echo (R2) relaxation rates during contrast agent bolus administration generates vessel vortex curves that allow the extraction of vascular architecture mapping parameters representative of, eg, vessel type, vessel radius, or CBV in the underlying voxel. Averaged whole-brain parametric maps were calculated for 9 parameters, and VOI analysis was conducted on the basis of a standardized brain atlas and individual cortical GM and WM segmentation. Prevalence of vascular risk factors among subjects (n = 106; mean age, 39.2 [SD, 12.5] years; 56 women) was similar to those in the German population. Compared with WM, we found cortical GM to have larger mean vascular calibers (5.80 [SD, 0.59] versus 4.25 [SD, 0.62] P < .001), increased blood volume fraction (20.40 [SD, 4.49] s-1 versus 11.05 [SD, 2.44] s-1; P < .001), and a dominance of venous vessels. Distinct microvascular profiles emerged for cortical GM, where vascular architecture mapping vessel type indicator differed, eg, between the thalamus and cortical GM (mean, -2.47 [SD, 4.02] s-2 versus -5.41 [SD, 2.84] s-2; P < .001). Intraclass correlation coefficient values indicated overall high test-retest reliability for vascular architecture mapping parameter mean values when comparing multiple scans per subject. Whole-brain vascular architecture mapping in the adult brain reveals region-specific microvascular profiles. The obtained parameter reference ranges for distinct anatomic and functional brain areas may be used for future vascular architecture mapping studies on cerebrovascular pathologies and might facilitate early discovery of microvascular changes, in, eg, neurodegeneration and neuro-oncology.

Functional and structural neuroretinal disorders in HIV Controllers. Prospective cohort study.

To estimate the prevalence and cumulative incidence of neuro-retinal-disorders (NRD) in HIV-controllers. Prospective, single-centre, cohort study of people living with HIV (PLWH): elite-controllers, long-term-non-progressors and early diagnosed. The study compared "HIV-controllers" (including elite-controllers and long-term-non-progressors), who were not on antiretroviral therapy (ART), and "HIV-treatment" (HIV-infected subjects with a recent diagnosis and on ART). A matched cohort of "non-HIV subjects" was created. NRD was defined as at least one altered (not normal) ophthalmological parameter (functional or structural). Functional (visual acuity, contrast sensitivity, chromatic vision, visual field) and structural parameters (ganglion cells, macular nerve fibre layer, peripapillary nerve fibre layers, vascular calibre) as well as quality of life (Medical Outcomes Study-HIV Short Form-30) were assessed. Between March 2012 and November 2015, the study included all HIV-controllers (16 elite-controllers, 1 long-term-non-progressor), 11 HIV-treatment and 16 non-HIV. Prevalence of NRD at baseline was 88.2% (15/17, 95% CI: 65.7%-96.7%), 90.9% (10/11, 95% CI: 62.3%-98.4%) and 56.3% (9/16, 95% CI: 33.2%-76.9%), respectively. Cumulative incidence at 3 years was 50% (1/2), 100% (1/1) and 33.3% (2/6), respectively. None of the participants manifested ocular clinical symptoms. Three years later, prevalence of NRD was 92.3% (12/13, 95% CI: 66.7%-98.6%), 75% (6/8, 95% CI: 40.9%-92.9%) and 50.0% (7/14, 95% CI: 26.8%-73.2%), respectively. Contrast sensitivity and structural parameters were globally the most affected among PLWH. Quality of life (total score) [median (interquartile range)] at baseline and 3 years was 82 (71-89) and 74 (63.5-79.25) in HIV-controllers and 80 (73-88) and 88 (83-92) in HIV-treatment. HIV-controllers and those individuals on ART presented a higher percentage of NRD than non-HIV. Our results suggest that NRD could be a biomarker of ocular aging among PLWH.

Deep Learning‐Enabled Vasculometry Depicts Phased Lesion Patterns in High Myopia Progression

PurposeTo investigate the potential phases in myopic retinal vascular alterations for further elucidating the mechanisms underlying the progression of high myopia (HM). MethodsFor this retrospective study, participants diagnosed with high myopia at Beijing Tongren Hospital were recruited. Based on bionic mechanisms of human vision, an intelligent image processing model was developed and utilized to extract and quantify the morphological characteristics of retinal vasculatures in different regions measured by papilla-diameter (PD), including vascular caliber, arteriole-to-venule ratio (AVR), tortuosity, the angle of the vascular arch (AVA), the distance of the vascular arch (DVA), density, fractal dimension, and venular length. In addition, the optic disc and the area of peripapillary atrophy (PPA) were also quantified. The characteristics of the overall population, as well as patients aged less than 25 years old, were compared by different genders. Univariate and multiple linear regression analyses were conducted to investigate the correlation of retinal vasculature parameters with PPA width, and detailed trends of the vascular indicators were analyzed to explore the potential existence of staged morphological changes. FindingsThe study included 14,066 fundus photographs of 5775 patients (aged 41.2 ± 18.6 years), of whom 7379 (61.2 %) were female. The study included 12,067 fundus photographs of 5320 patients (aged 41.2 ± 18.6 years). Significant variations in the morphological parameters of retinal vessels were observed between males and females. After adjusting for age and sex, multiple linear regression analysis showed that an increased PPA width ratio was associated with lower AVA (1PD), DVA (1PD), vascular caliber (0.5–1.0 PD), tortuosity (0.5–1.0 PD), density and fractal dimension (all P < 0.001, Spearman’s ρ < 0). Overall, the changes in retinal vascular morphology showed two phases: tortuosity (0.5–1.0PD) and AVA (1PD) decreased rapidly in the first stage but significantly more slowly in the second stage, while vascular density and fractal dimension showed a completely opposite trend with an initial slow decline followed by a rapid decrease. ConclusionsThis study identified two distinct phases of retinal vascular morphological changes during the progression of HM. Traction lesions were predominant in the initial stage, while atrophic lesions were predominant in the later stage. These findings provide further insight into the development mechanism of HM from the perspective of retinal vasculature.

Sociodemography, diabetes mellitus clinical parameters, and retinal morphology as predictors of neurodegeneration in preclinical diabetic retinopathy

Abstract PURPOSE: The current prediction of preclinical diabetic retinopathy (DR) in asymptomatic patients with diabetes mellitus (DM) is limited due to a lack of suitable indicators. This study aimed to identify the predictors of neurodegenerative changes in type 2 DM patients during the preclinical stage of DR using sociodemographic and DM clinical parameters and retinal morphology. METHODS: Fifty-six adult DM participants (mean age: 40.41 ± 7.281 years) were classified into three groups: DM without DR, DM with mild nonproliferative DR (NPDR), and DM with moderate-to-severe NPDR. Demographic data, including age, gender, race, DM duration, glycated hemoglobin levels, household income, comorbidities, and insulin dependency, were collected. Retinal morphology, including macular retinal layer thickness, peripapillary retinal nerve fiber layer, and vascular caliber, were analyzed. Multinomial logistic regression models explored these factors’ influence on NPDR prediction. RESULTS: Participants with moderate-to-severe NPDR were less likely to have DM without comorbidities (odds ratio [OR]: 0.048, 95% confidence interval [CI]: 0.003–0.823, P = 0.036). Those with longer DM duration were 27% more likely to develop moderate-to-severe NPDR (OR: 1.272, 95% CI: 1.035–1.564, P = 0.022). Retinal morphology parameters did not predict NPDR risk and severity levels in DM patients, except for mild NPDR, which had a 1.05 times higher risk of wider central retinal arteriolar equivalent (CRAE) (OR: 1.052, 95% CI: 1.002–1.105, P = 0.043). CONCLUSION: DM duration, comorbidity presence, and widened CRAE are critical parameters for assessing neurodegenerative changes in preclinical DR. These parameters could be incorporated into DR screening programs to mitigate NPDR progression and enhance long-term visual outcomes of DM patients.

Three-Year Follow-Up Study Investigating Changes in Retinal Vascular Morphology and the Relationship with Diabetic Retinopathy in Children with Type 1 Diabetes Mellitus.

This study aimed to investigate changes in retinal microvascular morphology and associated factors, and their relationship with diabetic retinopathy (DR) in children with type 1 diabetes mellitus (T1DM). Thirty-eight children enrolled in this 3-year follow-up study underwent complete ophthalmic examinations including fundus photography. Retinal vascular parameters were measured automatically and compared between baseline and follow-up. Multiple linear regression was used to investigate factors affecting changes in vascular parameters. Binary logistic regression was used to analyze the relationship between retinal microvascular morphology and DR. The caliber of all retinal vessels (within 1-1.5 papillary diameter [PD] from the center of the optic disc, p = 0.030; 1.5-2 PD, p = 0.003), arterioles, and venules (1.5-2 PD, p = 0.001) was narrower in nearly all regions in the follow-up group compared with the baseline group. Vascular tortuosity increased in the central part of the retina and decreased in the periphery. The density (1-1.5 PD, p = 0.030) and fractal dimension (p = 0.037) of retinal vessels were increased at the end of the follow-up compared with baseline. Retinal vascular caliber was independently correlated with DR (odds ratio 0.793 [95% confidence interval 0.633-0.993]; p = 0.044). Retinal microvascular morphology in children with T1DM varied with the disease course. Narrower retinal vessels may be an independent risk factor for DR. Results of this study emphasized the importance of regular follow-up of fundus vascular morphology for the detection of early DR in children with T1DM.

Hemoglobin levels are associated with retinal vascular caliber in a middle-aged birth cohort

Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (Bmales = 0.068 [0.001; 0.135], Bfemales = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases.

Bronquiolitis obliterante posinfecciosa secundaria a adenovirus

Bronchiolitis obliterans is a rare chronic obstructive respiratory disease secondary to damage of the lower respiratory tract causing inflammation and partial or total obliteration of it. There are different causes, being infectious the most frequent in pediatrics, mainly due to adenovirus. We present the case of an 18-month-old male infant with a history of admission to the Pediatric Intensive Care Unit at 8 months of age due to bronchitis secondary to respiratory syncytial virus and adenovirus. After this episode, he presented persistent respiratory distress and pathological pulmonary auscultation. High resolution pulmonary computed tomography showed a mosaic pattern with areas of air trapping and decreased vascular caliber in the affected areas, findings suggestive of bronchiolitis obliterans.

Retinal vessel caliber and cognitive performance: the multi-ethnic study of atherosclerosis (MESA).

Retinal vessel calibers share anatomic and physiologic characteristics with the cerebral vasculature and can be visualized noninvasively. In light of the known microvascular contributions to brain health and cognitive function, we aimed to determine if, in a community based-study, retinal vessel calibers and change in caliber over 8years are associated with cognitive function or trajectory. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort who completed cognitive testing at Exam 5 (2010-2012) and had retinal vascular caliber measurements (Central Retinal Artery and Vein Equivalents; CRAE and CRVE) at Exam 2 (2002-2004) and Exam 5 were included. Using multivariable linear regression, we evaluated the association of CRAE and CRVE from Exam 2 and Exam 5 and their change between the two exams with scores on tests of global cognitive function (Cognitive Abilities Screening Instrument; CASI), processing speed (Digit Symbol Coding; DSC) and working memory (Digit Span; DS) at Exam 5 and with subsequent change in cognitive scores between Exam 5 and Exam 6 (2016-2018).The main effects are reported as the difference in cognitive test score per SD increment in retinal vascular caliber with 95% confidence intervals (CI). A total of 4334 participants (aged 61.6 ± 9.2years; 53% female; 41% White) completed cognitive testing and at least one retinal assessment. On multivariable analysis, a 1 SD larger CRAE at exam 5 was associated with a lower concomitant CASI score (-0.24, 95% CI -0.46, -0.02). A 1 SD larger CRVE at exam 2 was associated with a lower subsequent CASI score (-0.23, 95%CI -0.45, -0.01). A 1 SD larger CRVE at exam 2 or 5 was associated with a lower DSC score [(-0.56, 95% CI -1.02, -0.09) and -0.55 (95% CI -1.03, -0.07) respectively]. The magnitude of the associations was relatively small (2.8-3.1% of SD). No significant associations were found between retinal vessel calibers at Exam 2 and 5 with the subsequent score trajectory of cognitive tests performance over an average of 6years. Wider retinal venular caliber was associated with concomitant and future measures of slower processing speed but not with later cognitive trajectory. Future studies should evaluate the utility of these measures in risk stratification models from a clinical perspective as well as for screening on a population level.

Artificial Intelligence-based quantitative evaluation of retinal vascular parameters in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) may result in increased metabolism and abnormalities in microcirculation. The fractal dimension (Df) of retinal vessels has been shown to be related to the pathology of a number of ophthalmic disorders, but it hasn't been investigated in TAO. We analyzed 1078 participants aged 18 to 72 (548 healthy volunteers and 530 TAO). Images were captured using a non-mydriatic 45-degree fundus camera. Baseline retinal characteristics, such as vessel width, tortuosity, and Df were measured using semiautomated software from fundus images. The average retinal parameters were compared between the two groups. The receiver operation curve (ROC) was used to assess the diagnostic efficacy of various retinal vascular parameters for TAO. Despite controlling for potential confounding variables, Df, vessel width, and tortuosity significantly increased in TAO compared to healthy volunteers. Compared to active TAO, patients in the inactive phase had a larger retinal venous caliber (p < 0.05), but there was no difference in Df or arterial caliber. Moderate and severe cases had a higher Df compared with mild cases (EUGOGO guidelines). The area under the ROC for Df, tortuosity, and vascular caliber in the diagnosis of TAO was 0.904 (95% CI: 0.884-0.924), 0.638 (95% CI: 0.598-0.679), and 0.617 (95% CI: 0.576-0.658), respectively. Due to its accessibility, affordability, and non-invasive nature, retinal vascular Df may serve as a surrogate marker for TAO and might be used to identify severe cases. With relatively high diagnostic performance, the Df is of some utility for the detection of TAO.

The State of Hemodynamics of Retinal Vessels in Primary Open-angle Glaucoma in Patients With Type 2 Diabetes Mellitus

Objective: to study the features of linear blood flow rate with central artery and retinal vein calibration in patients with POGC and type 2 diabetes. Examined 220 eyes (110 patients) with type 2 diabetes and 40 eyes (20 patients) with PAH without diabetes. The average age — 58 years old — 0,35. In addition to the common methods of research were: ophthalmoscopy with Goldman lens, binocular ophthalmoscope (Schepevsa), and lens Volk-90,0D (USA), gonioscopy with lenses (Krasnova, Goldman), tonometry by Maccov, NIidek (Japan) pneumototometry NT-2000, simplified tonography for Nesterov, OCT optical nerve disc and yellow spot Carl Zeiss Cirrus, HD OCT Model 4000/5000 Germany), OCT retinal vessels with calibre meter (Cirrus HD-Octiss Ultrasonic), Carl Ultrasonic (ISS) Central artery vessels and retinal veins (UZ — expert class system Sono Scapesq), ultrasound of the eyes. The data are processed statistically. In patients with PSA with SD 2 type of LSC reduction in the CAC at the initial and advanced stages up to 12.5 0.66 cm/s and 11 0.46 cm/s, with blood flow slowing in the CNS-LCC vessels 8.0.5 cm/s and 9.0 0.52 cm/s. In addition, the vascular calibre of the CAC increased to 91.5 0.67 μm and 93.5 0.65 μm at the initial and advanced stages of glaucoma, and the vascular size of the CAC was reduced to -97.6 0.19 μm at 75% and 93.5 0.9 μm at 50%, respectively, and expanded to 141.5 0.7%,7%. Revealed microcirculatory disorders in retinal vessels at POGC with type 2 diabetes allow recommending patients to conduct adequate therapy.

Anatomical Study of the Application of a Galeo-Pericranial Flap in Oral Cavity Defects Reconstruction.

Oral cavity defects occur after resection of lesions limited to the mucosa, alveolar gum, or minimally affecting the bone. Aiming at esthetical and functional improvements of intraoral reconstruction, the possibility of harvesting a new galeo-pericranial free flap was explored. The objective of this study was to assess the technical feasibility of flap harvesting through anatomical dissections and surgical procedure simulations. Ten head and neck specimens were dissected to simulate the surgical technique and evaluate the vascular calibers of temporal and cervical vessels. The procedure was therefore reproduced on a revascularized and ventilated donor cadaver. Anatomical dissections demonstrated that the mean cervical vascular calibers are compatible with superficial temporal ones, proving to be adequate for anastomosis. Perforating branches of the superficial temporal vascularization nourishing the pericranium were identified in all specimens. In conclusion, blood flow presence was recorded after anastomosing superficial temporal and facial vessels in the revascularized donor cadaver, demonstrating both this procedure's technical feasibility and the potential revascularization of the flap and therefore encouraging its potential in vivo application.

Characterizing Macular Neovascularization in Myopic Macular Degeneration and Age-Related Macular Degeneration Using Swept Source OCTA.

Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA. Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out. Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55±19 and 75±8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p<0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape's regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p>0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters. While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.

Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy.

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes. Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (α-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction. Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency.

White matter microstructural integrity is associated with retinal vascular caliber in adolescents with bipolar disorder

ObjectiveReduced white matter integrity is observed in bipolar disorder (BD), and is associated with cardiovascular risk in adults. This topic is underexplored in youth, and in BD, where novel microvascular measures may help to inform understanding of the vascular-brain connection. We therefore examined the association of retinal vascular caliber with white matter integrity in a cross-sectional sample of adolescents with and without BD. MethodsEighty-four adolescents (n = 42 BD, n = 42 controls) completed retinal imaging, yielding arteriolar and venular caliber. Diffusion tensor imaging measured white matter fractional anisotropy (FA). Multiple linear regression tested associations between retinal vascular caliber and FA in regions-of-interest; corpus callosum, anterior thalamic radiation, uncinate fasciculus, and superior longitudinal fasciculus. Complementary voxel-wise analyses were performed. ResultsArteriolar caliber was elevated in adolescents with BD relative to controls (F(1,79) = 6.15, p = 0.02, η2p = 0.07). In the overall sample, higher venular caliber was significantly associated with lower corpus callosum FA (β = −0.24, puncorrected = 0.04). In voxel-wise analyses, higher arteriolar caliber was significantly associated with lower corpus callosum and forceps minor FA in the overall sample (β = −0.46, p = 0.03). A significant diagnosis-by-venular caliber interaction on FA was noted in 5 clusters including the right retrolenticular internal capsule (β = 0.72, p = 0.03), corticospinal tract (β = 0.72, p = 0.04), and anterior corona radiata (β = 0.63, p = 0.04). In each instance, venular caliber was more positively associated with FA in BD vs. controls. ConclusionRetinal microvascular measures are associated with white matter integrity in BD, particularly in the corpus callosum. This study was proof-of-concept, designed to guide future studies focused on the vascular-brain interface in BD.

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.

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.

Gastrointestinal: Unusual pathology of an anorectal lesion mimicking a benign laterally spreading tumor.

A 70-year-old woman was referred to our institution for the diagnosis and treatment of an anorectal lesion detected on colonoscopy performed at a previous hospital for hematochezia. Colonoscopy revealed a 32-mm flat elevated lesion in the lower rectum with an anal component extending to the dentate line (Fig. 1a). Chromoendoscopy with indigo carmine spraying demonstrated a papillary surface (Fig. 1b). Magnifying endoscopy with narrowband imaging (NBI) displayed an irregular vessel resembling the intrapapillary capillary loop (IPCL) of the Japan Esophageal Society Classification Type B1 (Fig. 1c). Magnifying endoscopy with 0.05% crystal violet staining revealed the absence of discernible glandular ducts, hindering the evaluation of the pit pattern (Fig. 1d). The endoscopic appearance resembled a large adenoma or condyloma acuminatum; however, the absence of a pit pattern indicated that the lesion was covered with squamous epithelium and not columnar. Moreover, the irregular vessel pattern suggested a neoplastic lesion. Based on these observations, the lesion was diagnosed as a neoplasm originating from the squamous epithelium of the anal canal. Thus, we performed endoscopic submucosal dissection for complete elimination. Histological examination revealed a papillary growing squamous cell carcinoma (SCC) exhibiting low-grade and high-grade atypia and abundant dilated vessels (Fig. 2a). The tumor extended from the anal transitional zone (ATZ) to the rectum and entrapped the rectal crypts (Fig. 2b). Some tumor cells had a clear cytoplasm, indicative of koilocytosis (Fig. 2c), and positive p16 immunohistochemical staining suggested human papillomavirus (HPV) infection (Fig. 2d). The final diagnosis was HPV-associated SCC in situ originating from the ATZ with rectal extension. Anal canal cancer (ACC) is a rare disease that accounts for only 0.3% of all malignancies and is strongly associated with high-risk HPV (HPV-16 and HPV-18). This case was unusual because of the extensive infiltration of the columnar epithelium. Therefore, it might be misidentified as a rectal adenoma. Early ACC shows irregular vessel patterns reminiscent of esophageal SCC on magnified endoscopic NBI, which has been reported to be useful in diagnosing ACC. However, laterally spreading tumor (LST) can exhibit similar irregular capillary vessels. The difference in endoscopic appearance between ACC and LST can be explained by their different epithelial anatomies. ACC develops in the squamous cell epithelium and has no orifice or crypt. In contrast, LST originates from the columnar epithelium and has crypt openings. Condyloma acuminatum has a similar endoscopic appearance but with milder vascular dilatation and caliber changes. In conclusion, HPV-associated anal canal cancer can be suspected in papillary tumors with an irregular esophageal SCC-like vascular pattern and absence of glandular structures. Piecemeal endoscopic mucosal resection can be selected for large adenomas; conversely, en bloc resection is the preferred method for ACC to mitigate the risk of recurrence. To ensure the implementation of appropriate treatment, more attention should be paid to lesions extending along the anal canal to the rectum.

The Physics of Stroke

Flow of fluids in channels obey the natural law of Physics. It is dependent on force of propulsion, length of channel, caliber of channel and viscosity of fluid flowing through. In humans, blood flow to the brain obeys these laws. When perturbed by disease, flow and oxygen delivery are compromised resulting in cerebrovascular disease or stroke. Flow to the human brain depends on the force generated by the heart, viscosity of blood, length of the vessels, and diameter of the vascular channels with their variability. In normal situation, the cerebrovascular vessels can automatically regulate itself to ensure adequate cerebral perfusion. With Atherosclerotic Cardiovascular disease in the cerebral vasculature, flow dynamics is deranged and the result is the disease called stroke. Atherosclerotic cardiovascular diseases make the vessels stiff thus increasing intraluminal pressure. This damages the inner lining, the endothelium, and prepares grounds for the development of plaques. Plaques narrow vascular caliber increasing flow pressure at the narrow point but decreasing it beyond that point. The flow ceases to be laminar and becomes turbulent. When the plaques are ruptured by the high pressure at the points of narrowing, the blood coagulation cascade is activated and blood viscosity rises. These predispose to thrombus formation. The vessels thin out having lost elasticity of the walls rupturing easily with sudden blood pressure surges. In this state, the vessels lose their intrinsic ability to vary their diameters to cushion these effects. Blood flow becomes precarious. Cerebral tissue beyond such points suffer from ischemia and may actually have blood egress into them. Metabolism is impaired and higher cerebral function suffers resulting in cerebrovascular disease or stroke. Understanding how disease alters flow dynamics will equip clinicians better with the knowledge required to counter development of atherosclerotic cardiovascular diseases that result in stroke.