Changes In Vessel Diameter Research Articles

Abstract 333: Dynamic Limb-specific Metabolomics Reveals the Impact of Diabetes on Muscle and Vascular Responses to Ischemic Stress

Background: Type 2 Diabetes Mellitus (T2DM) increases cardiovascular risk, but the mechanisms are incompletely understood. Blood metabolomic signatures are altered in T2DM, but the impact of ischemic stress on the local skeletal muscle signature and T2DM-related vascular dysfunction is unknown. Methods: We recruited 38 subjects (18 healthy, 20 T2DM), placed an antecubital intravenous catheter, and performed ipsilateral brachial artery reactivity testing. Blood samples for plasma metabolite profiling were obtained at baseline and upon cuff release after 5 minutes of ischemia. Brachial artery diameter was measured at baseline and 1 minute after cuff release. Results: As expected, flow-mediated vasodilation was attenuated in subjects with T2DM (p<0.01). We confirmed known T2DM-associated baseline differences in plasma metabolites, including homocysteine, dimethylguanidino valeric acid and β-alanine (all p<0.05). Metabolites were significantly altered in response to experimental ischemia. Ischemia-induced metabolite changes that differed between groups included 5-hydroxyindoleacetic acid (Healthy: -27%; T2DM +14%), orotic acid (Healthy: +5%; T2DM -7%), trimethylamine-N-oxide (Healthy: -51%; T2DM +0.2%), and glyoxylic acid (Healthy: +19%; T2DM -6%) (all p<0.05). Serine, betaine, aminoisobutyric acid and anthranilic acid associated with vessel diameter at baseline, but only in T2DM (all p<0.05). Metabolite responses to ischemia were significantly associated with vasodilation extent, but primarily observed in T2DM. Within T2DM subjects, metabolite changes predicting change in vessel diameter included enrichment in amino acid, glycerophospholipid and propanoate metabolism (all p<0.05). Conclusion: Our study highlights potential impairments in muscle and vascular signaling at rest and during ischemic stress in T2DM. While metabolites change in both healthy and T2DM subjects in response to ischemia, a relationship between muscle metabolism and vascular function is modified in T2DM, suggesting that dysregulated muscle metabolism in T2DM may have direct effects on vascular function.

A generalized multi-scale line-detection method to boost retinal vessel segmentation sensitivity

Many chronic eye diseases can be conveniently investigated by observing structural changes in retinal blood vessel diameters. However, detecting changes in an accurate manner in face of interfering pathologies is a challenging task. The task is generally performed through an automatic computerized process. The literature shows that powerful methods have already been proposed to identify vessels in retinal images. Though a significant progress has been achieved toward methods to separate blood vessels from the uneven background, the methods still lack the necessary sensitivity to segment fine vessels. Recently, a multi-scale line-detector method proved its worth in segmenting thin vessels. This paper presents modifications to boost the sensitivity of this multi-scale line detector. First, a varying window size with line-detector mask is suggested to detect small vessels. Second, external orientations are fed to steer the multi-scale line detectors into alignment with flow directions. Third, optimal weights are suggested for weighted linear combinations of individual line-detector responses. Fourth, instead of using one global threshold, a hysteresis threshold is proposed to find a connected vessel tree. The overall impact of these modifications is a large improvement in noise removal capability of the conventional multi-scale line-detector method while finding more of the thin vessels. The contrast-sensitive steps are validated using a publicly available database and show considerable promise for the suggested strategy.

Ultrasound evaluation of infrapatellar fat pad impingement: An exploratory prospective study

BackgroundWe sought to determine whether there are ultrasound parameters that differ between knees with symptomatic fat pad synovial impingement and asymptomatic knees. MethodsA prospective study was performed in patients with clinical signs and symptoms of fat pad synovial impingement and asymptomatic controls. Eleven symptomatic knees and 10 asymptomatic controls were evaluated. Ultrasound imaging was performed before and after exercise. Evaluated parameters included largest fat lobule compressibility, subjective assessment of vascularity, largest vessel diameter, and subjective assessment of dynamic fat pad motion during flexion and extension. Receiver operating characteristic (ROC) curve analysis was used to assess whether changes in these parameters were different between symptomatic and asymptomatic knees. ResultsChange in the largest vessel diameter was greater and trended toward dilation in asymptomatic knees compared to symptomatic knees (mean: 0.83 vs. −0.02; P<0.001). No significant differences were observed between symptomatic and asymptomatic knees with respect to pre-exercise versus post-exercise states in subjective assessment of vascularity (P=0.131), fat pad motion (P=0.115), or percent change of the largest fat lobule (P=0.241). However, overall compressibility of the fat pad lobule was significantly diminished in the pre-exercise state in symptomatic knees compared to asymptomatic controls. ConclusionsThis study demonstrated a statistically significant change in the largest vessel diameter from pre- to post-exercise states between symptomatic and asymptomatic knees, as well as abnormal pre-exercise fat lobule compressibility in symptomatic knees. These findings show promise that with further research, ultrasound could have clinical utility in diagnosing infrapatellar fat pad impingement.

High-speed microscopy for in vivo monitoring of lymph dynamics.

The lymphatic system contributes to body homeostasis by clearing fluid, lipids, plasma proteins and immune cells from the interstitial space. Many studies have been performed to understand lymphatic function under normal conditions and during disease. Nevertheless, a further improvement in quantification of lymphatic behavior is needed. Here, we present advanced bright-field microscopy for in vivo imaging of lymph vessels (LVs) and automated quantification of lymphatic function at a temporal resolution of 2 milliseconds. Full frame videos were compressed and recorded continuously at up to 540 frames per second. A new edge detection algorithm was used to monitor vessel diameter changes across multiple cross sections, while individual cells in the LVs were tracked to estimate flow velocity. The system performance initially was verified in vitro using 6- and 10-μm microspheres as cell phantoms on slides and in 90-μm diameter tubes at flow velocities up to 4 cm/second. Using an in vivo rat model, we explored the mechanisms of lymphedema after surgical lymphadenectomy of the mesentery. The system revealed reductions of mesenteric LV contraction and flow rate. Thus, the described imaging system may be applicable to the study of lymphatic behavior during therapeutic and surgical interventions, and potentially during lymphatic system diseases.

Diagnostic Value of Transluminal Attenuation Gradient for the Presence of Ischemia as Defined by Fractional Flow Reserve and Quantitative Positron Emission Tomography

ObjectivesThe aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)–derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BackgroundIn addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. MethodsPatients with suspected coronary artery disease underwent coronary CTA and [15O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA–derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow ≤2.30 ml/min/g) and FFR (≤0.80) was determined. ResultsA total of 557 (91.9%) coronary arteries of 201 patients were included for analysis. TAG, TAG-CCO, and TDG did not discriminate between vessels with or without ischemia as defined by either PET or FFR. Furthermore, these parameters did not have incremental diagnostic accuracy over coronary CTA alone for the presence of ischemia as defined by PET and FFR. There was a significant correlation between TDG and TAG (r = 0.47; p < 0.001) and between TDG and TAG-CCO (r = 0.37; p < 0.001). ConclusionsTAG, TAG-CCO, and TDG do not provide incremental diagnostic value over coronary CTA alone for the presence of ischemia as defined by [15O]H2O PET and/or FFR. The lack of diagnostic value of contrast enhancement–based flow estimations appears related to coronary luminal dimension variability.

Development of an Experimental and Digital Cardiovascular Arterial Model for Transient Hemodynamic and Postural Change Studies: "A Preliminary Framework Analysis".

The ultimate goal of the present work is to aid in the development of tools to assist in the treatment of cardiovascular disease. Gaining an understanding of hemodynamic parameters for medical implants allow clinicians to have some patient-specific proposals for intervention planning. In the present work an experimental and digital computational fluid dynamics (CFD) arterial model consisting of a number of major arteries (aorta, carotid bifurcation, cranial, femoral, jejunal, and subclavian arteries) were fabricated to study: (1) the effects of local hemodynamics (flow parameters) on global hemodynamics (2) the effects of transition from bedrest to upright position (postural change) on hemodynamics, and (3) diffusion of dye (medical drug diffusion simulation) in the arterial system via experimental and numerical techniques. The experimental and digital arterial models used in the present study are the first 3-D systems reported in literature to incorporate the major arterial vessels that deliver blood from the heart to the cranial and femoral arteries. These models are also the first reported in literature to be used for flow parameter assessment via medical drug delivery and orthostatic postural change studies. The present work addresses the design of the experimental and digital arterial model in addition to the design of measuring tools used to measure hemodynamic parameters. The experimental and digital arterial model analyzed in the present study was developed from patient specific computed tomography angiography (CTA) scans and simplified geometric data. Segments such as the aorta (ascending and descending) and carotid bifurcation arteries of the experimental and digital arterial model was created from online available patient-specific CTA scan data provided by Charite' Clinical and Research Hospital. The cranial and coronary arteries were simplified arterial geometries developed from dimensional specification data used in previous work. For the patient specific geometries, a MATLAB code was written to upload the CTA scans of each artery, calculate the centroids, and produce surface splines at each discrete cross section along the lumen centerline to create the patient specific arterial geometries. The MATLAB code worked in conjunction with computer aided software (CAD) Solidworks to produce solid models of the patient specific geometries and united them with the simplified geometries to produce the full arterial model (CAD model). The CAD model was also used as a blueprint to fabricate the experimental model which was used for flow visualization via particle imaging velocimetry (PIV) and postural change studies. A custom pulse duplicator (pulsatile pump) was also designed and developed for the present work. The pulse duplicator is capable of producing patient-specific volumetric waveforms for inlet flow to the experimental arterial model. A simple fluid structure interaction (FSI) study was also conducted via optical techniques to establish the magnitude of vessel diameter change due to the pulsatile flow. A medical drug delivery (dye dispersion and tracing) case was simulated via a dye being dispersed into the pulsatile flow stream to measure the transit time of the dye front. Pressure waveforms for diseased cases (hypertension & stenotic cases) were also obtained from the experimental arterial model during postural changes from bedrest (0°) to upright position (90°). The postural changes were simulated via attaching the experimental model to a tile table the can transition from 0° to 90°. The PIV results obtained from the experimental model provided parametric data such as velocity and wall shear stress data. The medical drug delivery simulations (experimental and numerical) studies produce time dependent data which is useful for predicting flow trajectory and transit time of medical drug dispersion. In the case of postural change studies, pressure waveforms were obtained from the common carotid artery and the femoral sections to yield pressure difference data useful for orthostatic hypotension analysis. Flow parametric data such as vorticity (flow reversal), wall shear stress, normal stress, and medical drug transit data was also obtained from the digital arterial model CFD simulations. Although the present work is preliminary work, the experimental and digital models proves to be useful in providing flow parametric data of interest such as: (1) normal stress which is useful for predicting the magnitude of forces which could promote arterial rupture or dislodging of medical implants, (2) wall shear stress which is useful for analyzing the magnitude of drug transport at the arterial wall, (3) vorticity which is useful for predicting the magnitude of flow reversal, and (4) arterial compliance in the case of the experimental model which could be useful in the efforts of developing FSI numerical simulations that incorporates compliance which realistically models the flow in the arterial system.

Retinal Vessel Oxygen Saturation and Vessel Diameter in Inactive Graves Ophthalmopathy.

To investigate whether inactive thyroid-associated ophthalmopathy (TAO) affects retinal oxygen saturation and/or vessel diameter. Via an observational case-control study, retinal circulation was measured in patients with inactive TAO (mild, moderate, and severe) and normal subjects by retinal oximetry. Complete ophthalmologic examination, including noncontact tonometry and Hertel exophthalmometry, was performed; history of smoking and dysthyroid disease were recorded. Analysis of variance or the Kruskal-Wallis test was used to compare oximetry values between TAO and controls. Simple linear regression was used to analyze the correlation of Hertel, smoking, and intraocular pressure with oximetry values. Seventy-six eyes were enrolled: 19 controls, and 17 mild, 21 moderate, and 19 severe inactive TAO. Retinal oxygen saturation did not change significantly in inactive TAO versus controls; arteriole saturation: severe, 95.7% ± 7.0%; moderate, 93.2% ± 3.9%; mild, 90.3% ± 4.8%; and controls, 93.1% ± 6.4%; vein saturation: severe, 57.4% ± 7.1%; moderate, 59.0% ± 7.0,; mild, 56.3% ± 7.9%; and controls, 58.5% ± 6.5%; arteriovenous saturation: severe, 38.3% ± 8.0%; moderate, 34.2% ± 7.1%; mild, 33.9% ± 6.8%; and controls, 34.6% ± 5.9%. However, retinal venous diameter with severe TAO (137.3 ± 12.5 μm) significantly decreased in comparison with controls (148.8 ± 10.2 μm, p = 0.017). Otherwise, no significant change in vessel diameter was found between TAO and controls. No statistically significant correlations were found between Hertel values or intraocular pressure and oximetry values. However, there was a positive significant correlation between smoking and arteriovenous oxygen saturation (p = 0.017, β = 4.61). In inactive TAO versus controls, retinal oxygen saturation fluctuated and could be affected by smoking; however, the retinal venous diameter only decreased significantly for severe TAO. This implies that TAO may affect retinal circulation; this effect could be accelerated by smoking.

Dynamic changes in retinal vessel diameter during acute hyperglycemia in type 1 diabetes

AimsTo investigate changes in retinal vessel diameter during acute hyperglycemia in patients with type 1 diabetes. MethodsWe conducted a study on 11 subjects with type 1 diabetes. Euglycemia was maintained for 3h followed by induction of hyperglycemia and simultaneous bolus of rapid acting insulin. Two fundus photos were captured during euglycemia and five fundus photos, blood glucose and blood pressure were taken every 30min for 2.5h post-prandial. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were measured over the study visit and examined using generalized linear mixed models. ResultsIn a multivariate mixed model, mean CRAE and CRVE were reduced at 90min post-prandial in both zones B and C. In repeated measures analysis, arterioles exhibited a significant association with change in vessel caliber per change in blood glucose. Inconsistent effects of blood pressure on vessel diameter were also measured. ConclusionsWe document a change in retinal vessel diameter during acute hyperglycemia in persons with type 1 diabetes. Larger controlled studies are required to further investigate this phenomenon and to more accurately assess if hyperglycemia has direct effects on retinal vessel diameter.

Changes in retinal vessel diameters after intravitreal aflibercept in patients with diabetic macular edema

PurposeTo evaluate changes in retinal vessel diameters after loading doses with intravitreal aflibercept in patients with diabetic macular edema (DME).MethodsThis was a three months prospective, interventional study. We included 17 patients with DME, central retinal thickness &gt;300 μm and no active proliferative diabetic retinopathy. Previous treatment with any intravitreal vascular endothelial growth factor inhibitor was not allowed within 4 months prior to inclusion. All patients received 3 monthly intravitreal injections of aflibercept, and vessel diameters were evaluated at baseline and four weeks after the last injection. Retinal arterial and venous diameters were measured in 50‐degree disc‐centered images using the Oxymap model T1 (Oxymap, Reykjavik, Iceland) as the average diameter of the four major arterioles and venules from the four quadrants. Paired t‐test was used to test for differences in mean oxygen saturations from baseline to follow‐up.ResultsMedian age and duration of diabetes were 59.5 and 2.6 years at baseline. Median HbA1c and CRT were 65 mmol/mol and 336 μm, respectively, and 23.5% were women. Venous diameter decreased from baseline to follow‐up (157.9 μm vs. 153.2 μm, p = 0.03), whereas arterial diameter was unchanged (115.4 μm vs. 116.1, p = 0.70).ConclusionsRetinal venous diameter decreased after treatment with 3 monthly intravitreal injections of aflibercept in patients with DME, whereas no difference was found in the retinal arterial diameter. As previous studies have demonstrated that retinal venules dilate with increasing severity of diabetic retinopathy, our results suggest that treatment with intravitreal aflibercept causes positive changes to retinal vessel geometry.

Quantitative Characterization of Autoimmune Uveoretinitis in an Experimental Mouse Model.

To accurately evaluate the autoimmune inflammation, we aim to develop three quantitative measurements to monitor the inflammatory changes in the retina: retinal-choroidal thickness, major retinal vessel diameter, and electroretinography amplitudes. During a 21-day experimental period, eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography, fundus fluorescein angiography, and electroretinography in living mice, which were then subsequently killed for histologic assessments. On day 21 postimmunization, inflammation was observed both in vivo and in vitro. Fold change of retinal-choroidal thickness and major retinal vessel diameter in experimental autoimmune uveoretinitis mice were significantly greater than controls (P < 0.001). Both scotopic and photopic electroretinography amplitudes were significantly attenuated when compared with control mice (P < 0.01). Our results showed that these three quantifiable indicators provided an objective and accurate evaluation of autoimmune inflammation, which are in good correlations with the reported clinical and histopathologic scoring systems (P < 0.05). These three indicators will be useful to detect the small but significant differences in the severity of experimental autoimmune uveoretinitis for future longitudinally therapeutic studies.

Hyperoxia does not directly affect vascular tone in isolated arteries from mice.

Hospitalized patients often receive oxygen supplementation, which can lead to a supraphysiological oxygen tension (hyperoxia). Hyperoxia can have hemodynamic effects, including an increase in systemic vascular resistance. This increase suggests hyperoxia-induced vasoconstriction, yet reported direct effects of hyperoxia on vessel tone have been inconsistent. Furthermore, hyperoxia-induced changes in vessel diameter have not been studied in mice, currently the most used mammal model of disease. In this study we set out to develop a pressure-myograph model using isolated vessels from mice for investigation of pathways involved in hyperoxic vasoconstriction. Isolated conduit and resistance arteries (femoral artery and gracilis arteriole, respectively) from C57BL/6 mice were exposed to normoxia (PO2 of 80 mmHg) and three levels of hyperoxia (PO2 of 215, 375 and 665 mmHg) in a no-flow pressure myograph setup. Under the different PO2 levels, dose-response agonist induced endothelium-dependent vasodilation (acetylcholine, arachidonic acid), endothelium-independent vasodilation (s-nitroprusside), as well as vasoconstriction (norepinephrine, prostaglandin F2α) were examined. The investigated arteries did not respond to oxygen by a change in vascular tone. In the dose-response studies, maximal responses and EC50 values to any of the aforementioned agonists were not affected by hyperoxia either. We conclude that arteries and arterioles from healthy mice are not intrinsically sensitive to hyperoxic conditions. The present ex-vivo model is therefore not suitable for further research into mechanisms of hyperoxic vasoconstriction.

Diameter Changes of Retinal Vessels in Diabetic Retinopathy.

The diameter of retinal vessels is an important source of information about retinal blood flow and metabolism. The purpose of the present study is to review how diameter changes of retinal vessels contribute to the development of diabetic retinopathy and may be a marker of the prognosis of the disease. The early stages of diabetic retinopathy are accompanied with dilatation of the diameter of retinal vessels and reduced autoregulation. Diabetic retinopathy also shows regional differences in the macular area and the retinal periphery and accompanying differences in vascular reactivity in these areas. These differences may potentially become an important source of insight into the pathophysiology of the disease in the future. Diabetic retinopathy is accompanied with changes in the diameter regulation of retinal vessels. The potential of newly developed techniques for assessing retinal blood flow and metabolism, such as Doppler techniques, adaptive optics, and retinal oximetry, is promising and may potentially contribute to significant advances in our understanding of diabetic retinopathy which remains a major cause of visual impairment.

Recent versus chronic fine particulate air pollution exposure as determinant of the retinal microvasculature in school children

BackgroundMicrovascular changes may represent an underlying mechanism through which exposure to fine particulate matter with a diameter ≤ 2.5µm (PM2.5) contributes to age-related disease development. We investigated the effect of recent and chronic exposure to PM2.5 on the microcirculation, exemplified by retinal vessel diameters, using repeated measurements in 8- to 12-year-old children. Methods221 children (49.1% girls; mean age 9.9 years) were examined repeatedly (25 one, 124 two, and 72 three times) adding up to 489 retinal vessel examinations. Same-day exposure to PM2.5 was measured at school. In addition, recent (same and previous day) and chronic (yearly mean) exposure was modelled at the child's residence using a high-resolution interpolation model. Residential proximity to major roads was also assessed. Changes in retinal vessel diameters associated with recent and chronic exposures were estimated using mixed models, while adjusting for other known covariates such as sex, age, BMI, blood pressure and birth weight. ResultsEach 10µg/m³ increment in same-day exposure to PM2.5 measured at school was associated with 0.35µm (95% CI: 0.09–0.61µm) narrower retinal arterioles and 0.35µm (−0.03 to 0.73µm) wider venules. Children living 100m closer to a major road had 0.30µm (0.05–0.54µm) narrower arterioles. ConclusionsBlood vessel diameters of the retinal microcirculation of healthy school-aged children respond to same-day PM2.5 exposure. Furthermore, children living closer to major roads had smaller arteriolar diameters. Our results suggest that the microcirculation, with retinal microvasculature as a proxy in this study, is a pathophysiological target for air pollution in children.

Alpha Calcitonin Gene-Related Peptide Increases Cerebral Vessel Diameter in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis.

Delayed cerebral ischemia (DCI) is a life-threatening complication after subarachnoid hemorrhage. There is a strong association between cerebral vessel narrowing and DCI. Alpha calcitonin gene-related peptide (αCGRP) is a potent vasodilator, which may be effective at reducing cerebral vessel narrowing after subarachnoid hemorrhage (SAH). Here, we report a meta-analysis of data from nine in vivo animal studies identified in a systematic review in which αCGRP was administered in SAH models. Our primary outcome was change in cerebral vessel diameter and the secondary outcome was change in neurobehavioral scores. There was a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls (p < 0.0005, 95% CI 23.7–57.9). Neurobehavioral scores were reported in four publications and showed a standardized mean difference of 1.31 in favor of αCGRP (CI −0.49 to 3.12). We conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes.

ALTERED CEREBRAL VESSEL OSCILLATION FREQUENCIES AS A POSSIBLE CAUSE OF IMPAIRED AMYLOID CLEARANCE

Retinal vessels are similar to cerebral vessels in their structure and function. Using a non-invasive in-vivo technique, we demonstrated previously that retinal vessel response to flicker is altered in Alzheimer's disease (AD): patients with dementia due to AD (ADD) showed more emphasized and delayed reactive dilation. Interstitial fluid of gray matter appears to flow outward via perivascular spaces which are located alongside cerebral vessels being passively propulsed by vessels’ pulsatility. Impaired pulsatility resulting in impaired clearance may in part explain amyloid deposition in the brain. We aimed to elucidate whether retinal vessels’ pulsatility is changed an ADD or mild cognitive impairment (MCI). Three groups of participants were examined by Dynamic Vessel Analyzer (IMEDOS Systems): 11 patients, 76.2 (72.5 − 80.0) y.o. [median (1st. quartile − 3rd quartile)], with mild-to-moderate dementia due to probable AD fulfilling the standard diagnostic criteria (ADD); 20 patients, 69.2 (63.6 − 72.0) y.o. with mild cognitive impairment (MCI) due to AD, and 14 anamnestic healthy control subjects 67.1 (58.5 − 70.8) y.o. without cognitive impairment (HC). Oscillatory temporal changes of retinal vessel diameters were assessed during 40 s and were evaluated using mathematical signal analysis. The relative to the vessel diameter magnitude of arterial oscillations was higher in ADD. Power spectra of the temporal curves differed between the groups especially within low frequency range of 0 − 0.2 Hz. In arteries at very low frequencies < 0.05 Hz HC oscillations, characterized by the normalized area under the power spectrum, prevailed over ADD and MCI oscillations. At moderate low frequencies (0.05 − 0.2 Hz) ADD and most MCI oscillations prevailed over HC oscillations. In ADD and MCI power spectra shifted from very low to moderate low frequencies. Interestingly, the latter frequencies correspond to those reported for lymphatic vessels. The emphasized retinal arterial pulsation at moderate low frequencies in ADD and MCI group would be compatible with the view of compensatory upregulation in AD and strengthen the amyloid clearance hypothesis.

The effect of different adaptation conditions on the dynamic vessel analysis

Purpose : Retinal arterioles and venules dilate when stimulated with flickering light. This phenomenon is described as functional hyperemia. Flicker light stimulation is an established noninvasive means of assessing the endothelial function and the retinal autoregulation by continuous measurement of vessel diameters. Investigation of the flicker-induced retinal vasodilation, known as dynamic vessel analysis (DVA), is often conducted under reduced ambient lighting conditions but the influence of various adaptation levels is still unclear. This work aims to clarify whether light or dark adaptation affects the DVA. Methods : We studied 15 volunteers (8m, 7f, 24.7±2.4 years, one eye) using the Retinal Vessel Analyzer (Imedos Systems UG). Exclusion criteria were VA 2.0D, myopia 5 D and systemic diseases. We investigated four primary vessel segments (superior as well as inferior temporal artery (STa/ITa) and vein (STv/ITv)) located in a range from 0.5–2 disc diameters from the optic disc. For each volunteer DVA was performed three times in random order. DVA after light adaptation (129cd/m2) and after dark adaptation (0.02cd/m2) were performed according to the standard protocol timing (350s total time, 3 flicker cycles; Garhofer et al. 2010). Both the vaso-dilatation values and baseline diameters were analyzed. The effect on regulatory vessel diameter changes during the transition between dark and light adaptation was examined measuring only baseline diameters. For statistical analysis t-test and Wilcoxon test for paired samples were used. Results : Vaso-dilatation values and baseline diameters between light and dark adaptation showed no significant differences (STa: p=0.099/0.977, ITa: p=0.670/0.999, STv: p=0.156/0.820, ITv: p=0.065/0.955). The obtained baseline values during the transitional measure showed increased diameters after dark adaptation (STa: +7%, ITa: +6%, STv: +5%, ITv: +8% = group-means, referred to the baseline values under light adaption) which returned slowly (tau=100 s) to the baseline values under light adaption. Conclusions : The presented work revealed, that adaptation conditions have no effect on DVA following the standard timing. This means, in clinical practice DVA results would not be influenced by different ambient light conditions. However, dark adaptation leads to increased vessel diameters. The large time constant should be considered using short time DVA protocols.

Reactivity in the human retinal microvasculature measured during acute gas breathing provocations

Although changes in vessel diameter following gas perturbation have been documented in retinal arterioles and venules, these responses have yet to be quantified in the smallest vessels of the human retina. Here, using in vivo adaptive optics, we imaged 3–25 µm diameter vessels of the human inner retinal circulation and monitored the effects of altered gas-breathing conditions. During isocapnic hyperoxia, definite constrictions were seen in 51% of vessel segments (mean ± SD for pre-capillary arterioles −9.5 ± 3.0%; capillaries −11.8 ± 3.3%; post-capillary venules −6.3 ± 2.8%); these are comparable with responses previously reported in larger vessels. During isoxic hypercapnia, definite dilations were seen in 47% of vessel segments (mean ± SD for pre-capillary arterioles +9.8 ± 1.5%; capillaries +13.7 ± 3.8%; post-capillary venules +7.5 ± 4.2%); these are proportionally greater than responses previously reported in larger vessels. The magnitude of these proportional changes implies that the capillary beds themselves play an important role in the retinal response to changes in carbon dioxide levels. Interestingly, the distribution of microvascular responses shown here differs from our previously reported responses to flicker stimulation, suggesting differences in the way blood supply is coordinated following gas perturbation and altered neural activity.

Reduced vessel tone leads to vasodilation and decreased cerebral rigidity

Magnetic Resonance Elastography (MRE) measures elastic shear wave propagation in vivo to infer biomechanical properties non-invasively [Muthupillai, et al. (1995) Science;269:1854-1857.]. Models predict that tissue stiffness is influenced by changes of vascular properties [Parker, et al. (2016) PhysMedBiol;61:4890-4903.]. Cerebral blood supply is closely regulated by diameter changes of blood vessels. We here investigated the influence of vasodilation on cerebral brain stiffness with MRE. A healthy C57BL/6 mouse was anesthetized with isoflurane mixed in 100% O2. Vasodilation was induced by a hypercapnic challenge (isoflurane mixed in 95% O2 + 5% CO2). Brain stiffness was measured with a 3D spin-echo MRE sequence in a 7T animal MRI scanner under normocapnic and hypercapnic conditions. Vibration frequency was 1 kHz. Wave length and wave speed was observed to decrease significantly under hypercapnic conditions across the whole brain when compared to baseline. These changes correspond to a decrease in tissue rigidity. We conclude, therefore, that vasodilation via reducing vessel tone leads to a significant decrease in brain rigidity. Therefore, potential changes in cerebral blood flow due to physiological or pathological conditions should be considered when studying brain rigidity.

ATP‐Sensitive K+ Channels in Smooth Muscle Cells from Rat Mesenteric Lymph Vessels VESSELS

The ATP‐sensitive potassium (KATP) channel is expressed in plasma membranes of many types of smooth muscle cells (SMCs). It is disinhibited when intracellular ATP concentrations are reduced during conditions of metabolic stress, and the resulting K+ efflux through KATP channels mediates membrane hyperpolarization and SMC relaxation. However, in the lymphatic smooth muscle cells (LSMCs) of rhythmically contracting lymphatic vessels, KATP channels reportedly play an important role in regulating the basal rhythmic contractions that establish lymph flow even in the absence of overt metabolic challenge. The KATP channels in LSMCs also may participate in the dilator responses of lymphatic vessels (LVs) to nitric oxide, inflammatory mediators, and compromise lymph flow in other pathologies associated with oxidative stress1,2,3. Although it is recognized that the properties and the subunit composition of KATP channels show tissue‐specificity, the identity and properties of KATP channels in LSMCs are unknown. The goal of this study was to begin to define the function and properties of KATP channels in rat mesenteric LVs. Isolated rat mesenteric LVs were cannulated on glass pipettes, pressurized at 4.5–6 mmHg, and edge detection was used to continuously monitor changes in vessel diameter. Addition of the KATP channel agonist cromakalim (0.01 μM‐100 μM; half‐log units) progressively increased LV diameter and abolished rhythmic contractions (n=3). In contrast, addition of the KATP channel antagonist, glibenclamide (0.01 μM‐100 μM; half‐log units) resulted in no change in LV diameter but suppressed rhythmic contractions. The latter finding confirmed the important role of KATP channels as regulators of LV contractile function under basal conditions. Subsequently, we have begun to characterize KATP channel currents in SMCs freshly isolated from rat mesenteric LVs. Patch‐clamp studies in the cell‐attached mode reveal unitary K+ currents in symmetrical 145 K+ recording solutions at negative patch potentials near the resting membrane potential of LSMCs. Unitary amplitudes calculated over a range of negative patch potentials from −80 mV to −30 mV indicate a single‐channel conductance of ~ 37 pS. Thus, we have tentatively identified the KATP channel in rat LSMCs as a first step toward defining it's regulation by endogenous substances and pharmacological interventions that may alter lymph flow.Support or Funding InformationSupported by T32 GM106999 (BRG) and R21 CA187325‐01A1 (NJR) from the National Institutes of Health.

Stimulus-evoked changes in cerebral vessel diameter: A study in healthy humans

The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis. Specifically, we isolated the posterior cerebral artery (PCA) supplying each occipital lobe and quantified its vasodilation induced by visual stimulation. Stimulus-induced changes were strongest (∼30%) near primary visual cortex and progressively decreased in a non-linear fashion as a function of distance. Surprisingly, weak – albeit significant – changes (∼2%) were observed ∼70 mm from the visual cortex. This demonstrates that visual stimulation modulates vascular tone along the bulk of the PCA segment, and thus may have important implications for our understanding of functional hyperemia in healthy and diseased states.