LUNet: deep learning for the segmentation of arterioles and venules in high resolution fundus images.

Objective.This study aims to automate the segmentation of retinal arterioles and venules (A/V) from digital fundus images (DFI), as changes in the spatial distribution of retinal microvasculature are indicative of cardiovascular diseases, positioning the eyes as windows to cardiovascular health.Approach.We utilized active learning to create a new DFI dataset with 240 crowd-sourced manual A/V segmentations performed by 15 medical students and reviewed by an ophthalmologist. We then developed LUNet, a novel deep learning architecture optimized for high-resolution A/V segmentation. The LUNet model features a double dilated convolutional block to widen the receptive field and reduce parameter count, alongside a high-resolution tail to refine segmentation details. A custom loss function was designed to prioritize the continuity of blood vessel segmentation.Main Results.LUNet significantly outperformed three benchmark A/V segmentation algorithms both on a local test set and on four external test sets that simulated variations in ethnicity, comorbidities and annotators.Significance.The release of the new datasets and the LUNet model (www.aimlab-technion.com/lirot-ai) provides a valuable resource for the advancement of retinal microvasculature analysis. The improvements in A/V segmentation accuracy highlight LUNet's potential as a robust tool for diagnosing and understanding cardiovascular diseases through retinal imaging.

Retinal blood vessel calibre and vascular ageing in a general Spanish population: A EVA study.

INTRODUCTION: The aim of this work was to analyse the association of the retinal arteriolar calibre and the arteriole/venule index (AV index) with vascular ageing in a general population without previous cardiovascular disease. MATERIALS AND METHODS: Descriptive cross-sectional study. A total of 482 individuals without cardiovascular disease (mean age: 55.6 ± 14.2 years) were selected by random sampling, stratified by age and sex. The retinal arteriolar calibre was measured using digital fundus images of the back of the eye captured with a validated, semiautomatized and computer-assisted software (Index calculator). Vascular ageing was defined using three criteria based on the values of: (1) Carotid-femoral Pulse Wave Velocity (cfPWV), (2) Brachial-ankle Pulse Wave Velocity (baPWV) and (3) Carotid Intima-Media Thickness. RESULTS: The AV index and arteriolar calibre show a negative correlation with age, arterial pressure, cardiovascular risk and parameters of vascular structure and function (p < 0.001 in all cases). We found lower mean values of the AV index and arteriolar calibre in the individuals with early vascular ageing compared to those with healthy vascular ageing. AV index was negatively correlated with cfPWV ((ß=-2.9; 95% CI (-4.7; -1.1)), baPWV ((ß=-3.2; 95% CI (-5.4; -0.9)) and vascular ageing index ((ß=-1.7; 95% CI (-2.7; -0.7)). Arteriolar calibre showed a negative correlation with baPWV (ß=-0.1; 95% CI (-0.2; -0.1)). In the logistic regression analysis, lower values of AV index ((OR=0.01; 95% CI (0.01-0.10), OR=0.03; 95% CI (0.01-0.11) and OR=0.09; 95% CI (0.01-0.67)) were associated with EVA defined with cfPWV, baPWV and vascular ageing index respectively, and lower values of arteriolar calibre ((OR=0.71; 95% CI (0.55-0.91)) were associated with EVA defined with vascular ageing index. CONCLUSIONS: Lower values of AV index and retinal arteriolar calibre were associated with vascular ageing in a general Spanish population without previous cardiovascular disease.

Changes in physical activity behavior and development of cardiovascular risk in children.

The study aimed to investigate the association of changes in physical activity, screen time, and cardiorespiratory fitness (CRF) with development of body mass index (BMI), blood pressure (BP), and retinal microvascular health in children over four years. In 2014, 391 children aged 6-8 years were screened, and thereof 262 children were reexamined after four years following standardized protocols. Retinal arteriolar (CRAE) and venular diameters were measured by a retinal vessel analyzer. CRF was objectively assessed by a 20 m shuttle run, physical activity, and screen time by use of a questionnaire. Children who achieved higher CRF levels reduced their BMI (ß [95% CI] -0.35 [-0.46 to -0.25] kg/m2 per stage, P ≤ .001) and thereby developed wider CRAE (ß [95% CI] 0.25 [0.24 to 0.48] µm per stage, P = .03) at follow-up. Moreover, children with elevated or high systolic BP at baseline, but lower levels of screen time during the observation period, had wider CRAE at follow-up (ß [95% CI] -0.37 [-0.66 to -0.08] µm per 10 min/d, P = .013). Change in CRF was not directly associated with better microvascular health at follow-up. However, an increase of CRF over four years was associated with a reduced BMI and consequently wider retinal arterioles at follow-up. In children with elevated or high systolic BP, a reduction of screen time significantly improved retinal microvascular health as a primary prevention strategy to promote childhood health and combat development of manifest CV disease later in life.

Is the cortical capillary renamed as the transcortical vessel in diaphyseal vascularity?

A recent article published in Nature Metabolism, "A network of trans-cortical capillaries as a mainstay for blood circulation in long bones," explained the long bone vascularity. In the mouse model, the authors demonstrated hundreds of transcortical vessels (TCVs) commencing from the bone marrow and traversing the whole cortical thickness. They realized that TCVs were the same as bleeding vessels of periosteal bed observed in the human tibia and femoral epiphysis during surgery. TCVs expressed arterial or venous markers and were proposed to be the backbone of bone vascularity as 80% of arterial and 59% of venous blood distributed through them. This new evidence challenged the existence of the "cortical capillaries" stated in previous literature. We conducted a review of the existing literature to compare this model with those in earlier research. The bone vascularity model was explained by many researchers who did their work in animal models like pig, dog, rabbit, and mouse. The TCVs were identified in these animal model studies as cortical capillaries or vessels of cortical canals. Studies are scarce, showing the presence of TCVs in humans. The role of TCVs in human cortical vascularity remains ambiguous until the substantial evidence is collected in future studies.

[MICRO- AND ULTRASTRUCTURAL RECONSTRUCTION OF THE RAT SUBMANDIBULAR GLAND IN THE LATE STAGES OF EXPERIMENTAL TYPE 2 DIABETES MELLITUS].

Electron microscopic investigations of the animals' submandibular gland, conducted in 6 weeks of the experiment, established that ultrastructural changes increase in glandular cells of terminal secretory units in comparison with early period of the experiment. Serocytes have osmiophilic, rather small or picnotic nuclei. Perinuclear spaces of karyolemma are uneven, external nuclear membrane forms local protrusions. Electron density of the karyoplasm is significant, appearing homogenous, nuclei are not observed. Evident submicroscopic changes in blood capillaries of the submandibular gland in experimental diabetes mellitus indicate the impairment of blood-tissue barrier and transcapillary exchange. Deep destructive modifications of all branches of microcirculatory blood flow of the submandibular gland are observed in 8-week course of experimental diabetes mellitus. As compared with the 6th week of investigation, a reliable slight dilation of organ artery diameter, dilation of the diameter of interlobular arterioles, dilation of the diameter of intralobular (precapillary) arteriole and dilation of the capillary diameter were observed. Dilation, as compared to 6th weeks of the experiment, of postcapillary venules was observed. Compared to the indices of the 6th weeks of the experiment, an index of trophic activity of the submandibular gland tissuereaches its maximum meaning and an index of packing density of the capillaries reaches its minimum meaning. Capillary network loses delicate, tortuous pattern and often breaks due to destruction of the capillary component. Arteriovenous anastomoses dilate and blood from the arterioles flows into the venous bed avoiding destructed capillaries. Venules are dilated; thin-walled, retained fragments of the capillaries are significantly dilated in some areas. Swelling of connective tissue stroma and significant swelling of the interstitium are observed. Walls of the capillaries and venules are deformed. The walls of the arterioles are thickened due to plasmorrhagia, sclerosis and hyalinosis.

Morphology of the Vasculature and Blood Supply of the Brown Adipose Tissue Examined in an Animal Model by Micro-CT.

We performed micro-CT imaging of the vascular blood supply in the interscapular area of the brown adipose tissue in three mice with the use of intravascular contrast agent Aurovist™. Resulting 3D data rendering was then adapted into 2D resolution with visualization using false color system and grayscale images. These were then studied for the automatic quantification of the blood vessel density within this area. We found the highest most occurring density within arterioles or venules representing smaller blood vessels whereas with the increase of the vessel diameters a lower percentage rate of their presence was observed in the sample. Our study shows that micro-CT scanning in combination with Aurovist™ contrast is suitable for anatomical studies of interscapular area of brown adipose tissue blood vessel supply.

Relation between retinal vessel diameter and posterior segment optical coherence tomography variables in middle-aged Caucasians: the Northern Finland Birth Cohort Eye Study.

AIMS: Studying the relationship between retinal vessel diameter (RVD) with (1) macular thickness and volume, (2) retinal nerve fibre layer (RNFL), (3) ganglion cell-inner plexiform layer (GC-IPL) and (4) optic nerve head (ONH) in a population cohort of middle-aged Caucasians. METHODS: We collected data from 3070 individuals. We used a semiautomated computer-assisted programme to measure central retinal arteriolar equivalent and central retinal venular equivalent. Macular and ONH parameters were assessed by optical coherence tomography. RESULTS: Data from 2155 persons were analysed. A larger RVD was associated with a thicker macula and increased macular volume; each SD increase in average macular thickness and volume was associated with a 3.28 µm and a 3.19 µm increase in arteriolar diameter and a 5.10 µm and a 5.08 µm increase in venular diameter, respectively (p<0.001 for all). A larger rim area, greater GC-IPL and RNFL thicknesses were associated with larger RVD; each SD increase in rim area, GC-IPL thickness and RNFL thickness was associated with a 1.21 µm, 2.68 µm and a 3.29 µm increase in arteriolar diameter and a 2.13 µm, 4.02 µm and 5.04 µm increase in venular diameter, respectively (p<0.001 for all). CONCLUSIONS: Increased macular thickness, macular volume, GC-IPL thickness, RNFL thickness and optic nerve rim area were associated with larger RVDs in all subjects. This study clarified the anatomical correlations between both macular and ONH parameters with RVD for middle-aged Caucasians; these can represent a basis for further studies investigating the vascular aetiology of eye diseases.

Investigation into the diversity in the fractal dimensions of arterioles and venules in a microvascular network - A quantitative analysis.

Fractal dimension is a robust fractal parameter for estimating the morphology of vascular networks. It reflects the property of vascular networks that may vary and thus, differentiate between individual networks and/or identify physiological and pathological conditions. As such, fractal dimension differs also between arteriolar and venular compartments, yet the underlying reason is so far unclear. In order to understand the mechanisms behind these differences, we quantitatively analyzed the impacts of vessel attributes on the fractal dimension. Fractal dimension and vessel attributes given by vessel density (VD), vessel length density (VL), and diameter index (DI=VD/VL) were analyzed in three microvascular networks of the rat mesentery, which were reconstructed from experimental data. The results show that differences in diameter between arterioles and venules are primarily responsible for arterio-venous differences in fractal dimension. Moreover, multiple linear regression analysis demonstrates that the sensitivity of the variation of fractal dimension to vessel length and diameter varies with the type of the vessels. While the change of vessel length contributes 57.8 ±â€¯3.4% to the variation of arteriolar dimension, vessel diameter contributes 63.9 ±â€¯4.8% to the variation of venular dimension. The present study provides an explanation for the different fractal dimension and dimension variation in arteriolar and venular compartments. It highlights the importance of estimating the fractal dimensions of arterioles and venules separately, which will enhance the ability of feature extraction by fractal analysis in physiological and clinical application.

Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study.

BACKGROUND: Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. RESULTS: Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. CONCLUSIONS: Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.

Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study

ABSTRACT BACKGROUND: Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. RESULTS: Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. CONCLUSIONS: Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.

Retinal vascular diameters in relation to physical activity in Danish children - The CHAMPS Eye Study.

Our objective was to determine associations between retinal vascular caliber and physical activity (PA) in a school-based child cohort. In a prospective study, we created a childhood cumulative average PA-index using objectively measured PA (accelerometry) assessed at four periods between 2009 and 2015. Cumulative exposure to PA intensities was estimated. Cross-sectional examinations on biomarkers, anthropometry, and ophthalmological data including retinal fundus photographs were performed in 2015. Semi-automated measurements of retinal vascular diameters were performed and summarized into central retinal arteriolar and venular equivalents (CRAE, CRVE). We included 307 participants. Mean age in 2015 was 15.4 years (0.7). The mean CRAE and CRVE were 156.5 µm (2.8) and 217.6 µm (7.7), respectively. After adjusting for age, gender, and axial length, more time in PA was independently related to thinner retinal venules (ß-coefficient = -1.25 µm/%, 95% confidence interval = -2.20, -0.30, P < .01). Sedentary time was associated with wider venules (P < .01). Furthermore, birthweight (ß-coefficient = 0.56 µm/%, 95% confidence interval = 0.18, 0.95, P < .01) was associated with CRVE. Blood pressure was associated with thinner retinal arterioles (ß-coefficient = -0.19 µm/mmHg, 95% confidence interval = -0.36, -0.01, P = .04). We concluded that children with higher PA in childhood had thinner retinal venular caliber. Our results suggest that PA during childhood positively impacts the retinal microcirculation and that retinal vascular analysis may be a possible assessment to detect microvascular impairments in children with an increased risk of future cardiovascular disease.

Retinal Vascular Branching in Healthy and Diabetic Subjects.

Purpose: To measure the effect of nonproliferative diabetic retinopathy (NPDR) on retinal branching. To compare vascular branching in healthy and diabetic subjects with established biophysical models. Methods: Vascular bifurcations in arteries and veins were imaged in 17 NPDR and 26 healthy subjects with the Indiana adaptive optics scanning laser ophthalmoscope (AOSLO). Vessel measurements were grouped according to parent vessel diameters into large (≤50 ∼ <100 µm) and small (≤20 ∼ <50 µm) sizes. Vessel diameters and bifurcation angles were measured manually. Vascular diameters were compared with predictions of Murray's law using curve fitting. For analysis of bifurcation angles, two models from Zamir were compared: one based on the power required for blood pumping, the other based on drag force between blood and vascular wall. Results: For normal larger vessels, the exponent relating the parent and daughter branching diameters was significantly less than the value of 3 predicted by Murray's law (arteries: 2.59; veins: 1.95). In NPDR, the best-fit exponent was close to 3 for arteries but close to 2 in healthy subjects in veins, (arteries: 3.09; veins: 2.16). For both small arteries and veins, diabetics' exponent differed from healthy subjects (P < 0.01). Bifurcation angles in the healthy subjects (78° ± with a standard error (SE) of 0.9°) were not much different than in NPDR (79° ± SE 1.3°). The model based on minimizing pumping power predicted the measurements better than the one minimizing the vascular drag and lumen surface area. Conclusions: The relation between parent and daughter branch diameters changes in diabetes, but the branching angles do not.

Microvasculature of the California sea lion (Zalophus californianus) eye and its functional significance.

OBJECTIVE: To examine the ocular circulation in California sea lions (Zalophus californianus). ANIMALS STUDIED: Eyes were obtained postmortem from three sea lions that died while in captivity. PROCEDURES: Specimens from sea lions were investigated using scanning electron microscopy (SEM) of vascular corrosion casts. The thermal characteristics of live animal eyes were measured using an infrared imaging system. RESULTS: The major orbital artery of the sea lion was the ophthalmic artery. The artery was remarkably thick in diameter, showed a marked convolution and formed an ophthalmic rete around the optic nerve at the posterior pole of the eyeball. The long posterior ciliary artery terminates to form a prominent inner arterial circle at the pupillary margin. The iridial arteries originated from the arterial circle showing either a crimped or somewhat coiled course, extending toward the root of the iris and formed a root supplying a large amount of blood to the iris and ciliary bodies. The venules in the conjunctiva formed a well-developed venous plexus. The vortex veins showed a dilation and constriction at the site passing through the sclera. Thermographic examination revealed that the eye showed a higher degree of thermal emission than adjacent skin areas. CONCLUSIONS: These characteristics suggest that the ocular vasculature might play roles in thermoregulation as well as in hemodynamics by draining a large amount of blood so that the appropriate operating temperature for the eye can be maintained in a deep and cold aquatic environment.

Combined maceration procedure permits advanced microsurgical dissection of Thiel-embalmed specimens.

INTRODUCTION: Due to the realistic colour, texture conservation and preservation of biomechanical properties, Thiel-embalming is becoming the main embalming procedure for clinical courses and research based on human cadaver material. The aim of this study is to establish a new procedure that allows advanced microdissection of small vessels and intraorganic nerves in Thiel-embalmed material. MATERIAL AND METHODS/RESULTS: After a classical gross anatomical dissection, human hemipelves underwent repetitive application of 3 consecutive steps: (i) maceration with alloy of nitric acid and MiliQ water 1:10 for 24-48h. (ii) Immersion: the hemipelves were rinsed under tap water for 20-30min. and placed in a water bath for 1h. The nerves become more prominent due to the swelling and increased water content. (iii) microdissection under surgical microscope. To facilitate the organ visualization perfusion with polyurethane (Pu4ii, VasQtec®, Switzerland) in red/blue for arteries/veins respectively has been performed. CONCLUSION: By using the proposed procedure, we performed satisfactory microdissection on Thiel-embalmed samples. The combination with polyurethane vascular casting permits visualization of small arterioles and venules in a range of 20-25µm. The method is very suitable for demonstration of somatic and vegetative nerves. Branches of the sacral plexuses and autonomic nerves from the superior and inferior hypogastric plexus have been tracked up to the smallest intraorganic branches in a range of 12.5-15µm. In conclusion, the established combined procedure offers a new possibility for advanced microdissection, which will allow acquisition of clinically relevant information about organ specific micro- vascularization and innervation.

A statistical model of the penetrating arterioles and venules in the human cerebral cortex.

OBJECTIVE: Models of the cerebral microvasculature are required at many different scales in order to understand the effects of microvascular topology on CBF. There are, however, no data-driven models at the arteriolar/venular scale. In this paper, we develop a data-driven algorithm based on available data to generate statistically accurate penetrating arterioles and venules. METHODS: A novel order-based density-filling algorithm is developed based on the statistical data including bifurcating angles, LDRs, and area ratios. Three thousand simulations are presented, and the results validated against morphological data. These are combined with a previous capillary network in order to calculate full vascular network parameters. RESULTS: Statistically accurate penetrating trees were successfully generated. All properties provided a good fit to experimental data. The k exponent had a median of 2.5 and an interquartile range of 1.75-3.7. CBF showed a standard deviation ranging from ±18% to ±34% of the mean, depending on the penetrating vessel diameter. CONCLUSIONS: Small CBF variations indicate that the topology of the penetrating vessels plays only a small part in the large regional variations of CBF seen in the brain. These results open up the possibility of efficient oxygen and blood flow simulations at MRI voxel scales which can be directly validated against MRI data.

Comparison of Two Formulas Used to Calculate Summarized Retinal Vessel Calibers.

PURPOSE: To compare the Parr-Hubbard and Knudtson formulas to calculate retinal vessel calibers and to examine the effect of omitting vessels on the overall result. METHODS: We calculated the central retinal arterial equivalent (CRAE) and central retinal venular equivalent (CRVE) according to the formulas described by Parr-Hubbard and Knudtson including the six largest retinal arterioles and venules crossing through a concentric ring segment (measurement zone) around the optic nerve head. Once calculated, we removed one arbitrarily selected artery and one arbitrarily selected vein and recalculated all outcome parameters again for (1) omitting one artery only, (2) omitting one vein only, and (3) omitting one artery and one vein. All parameters were compared against each other. RESULTS: Both methods showed good correlation (r 2for CRAE = 0.58; r2 for CRVE = 0.84), but absolute values for CRAE and CRVE were significantly different from each other when comparing both methods (p < 0.000001): CRAE had higher values for the Parr-Hubbard (165 [± 16] µm) method compared with the Knudtson method (148 [± 15] µm). In addition, CRAE and CRVE values dropped for both methods when omitting one arbitrarily selected vessel each (all p < 0.000001). Arteriovenous ratio (AVR) calculations showed a similar change for both methods when omitting one vessel each: AVR decreased when omitting one arteriole whereas it increased when omitting one venule. No change, however, was observed for AVR calculated with six or five vessel pairs each. CONCLUSIONS: Although the absolute value for CRAE and CRVE is changing significantly depending on the number of vessels included, AVR appears to be comparable as long as the same number of arterioles and venules is included.

Cup-to-disc and arteriole-to-venule ratios in preterm birth.

AIMS: To investigate the influence of preterm birth on the optic disc and retinal vessels by measurements of cup-to-disc (C/D) ratio and arteriole-to-venule (A/V) ratio. METHODS: Eighty-three eyes of 42 preterm births were included. In the age- and sex-matched control group, 83 eyes of 42 full-term births were used. Fundus color photographs were taken. ImageJ software was used to calculate C/D and A/V ratios from the fundus images. RESULTS: Fundus photographs were taken at 8.01 ± 2.22 years of age for the preterm group and 8.01 ± 2.13 years of age for the control group. The mean gestational age of the preterm group was 27(4)/7 weeks (range, 24-34 weeks). The preterm group had significantly larger C/D ratio and smaller A/V ratio (mean ± standard deviation: 0.46 ± 0.12 and 0.59 ± 0.08, respectively) than the control group (0.36 ± 0.07 and 0.68 ± 0.07, respectively) after spherical equivalent refractive error was adjusted. CONCLUSIONS: Preterm birth is significantly associated with larger C/D ratio and smaller A/V ratio. These findings show the effect of preterm birth on the development of optic disc and retinal vessel development.

Characterization of blood flow in the mouse dorsal spinal venous system before and after dorsal spinal vein occlusion.

The availability of transgenic strains has made the laboratory mouse a popular model for the study of healthy and diseased state spinal cord (SC). Essential to identifying physiologic and pathologic events is an understanding of the microvascular network and flow patterns of the SC. Using 2-photon excited fluorescence (2PEF) microscopy we performed in vivo measurements of blood flow in the lower thoracic portion of the mouse dorsal spinal vein (dSV) and in the first upstream branches supplying it, denoted as dorsal ascending venules (dAVs). We found that the dSV had large radiculomedullary veins (RMVs) exiting the SC, and that flow in the dSV between pairs of RMVs was bidirectional. Volumetric flow increased in each direction away from the point of bifurcation. Flow in the upstream dAVs varied with diameter in a manner consistent with a constant distal pressure source. By performing ex vivo 2PEF microscopy of fluorescent-gel perfused tissue, we created a 3-D map of the dorsal spinal vasculature. From these data, we constructed a simple model that predicted changes in the flow of upstream branches after occlusion of the dSV in different locations. Using an atraumatic model of dSV occlusion, we confirmed the predictions of this model in vivo.

Ultra-high spatial resolution basal and evoked cerebral blood flow MRI of the rat brain.

Cerebral blood flow (CBF) is tightly coupled to metabolism and neural activity under normal physiological conditions, and is often perturbed in disease states. The goals of this study were to implement a high-resolution (up to 50×38µm(2)) CBF MRI protocol of the rat brain, create a digital CBF atlas, report CBF values for 30+ brain structures based on the atlas, and explore applications of high-resolution CBF fMRI of forepaw stimulation. Excellent blood-flow contrasts were observed among different cortical and subcortical structures. CBF MRI showed column-like alternating bright and dark bands in the neocortices, reflecting the layout of descending arterioles and ascending venules, respectively. CBF MRI also showed lamina-like alternating bright and dark layers across the cortical thicknesses, consistent with the underlying vascular density. CBF profiles across the cortical thickness showed two peaks in layers IV and VI and a shallow trough in layer V. Whole-brain CBF was about 0.89ml/g/min, with the highest CBF values found amongst the neocortical structures (1ml/g/min, range: 0.89-1.16ml/g/min) and the lowest CBF values in the corpus callosum (0.32ml/g/min), yielding a gray:white matter CBF ratio of 3.1. CBF fMRI responses peaked across layers IV-V, whereas the BOLD fMRI responses showed a peak in the superficial layers II-III. High-resolution basal CBF MRI, evoked CBF fMRI, and CBF brain atlas can be used to study neurological disorders (such as ischemic stroke).

The relationship between changes in body mass index and retinal vascular caliber in children.

OBJECTIVE: To examine the longitudinal relationship between changes in childhood body mass index (BMI) and retinal vascular caliber. STUDY DESIGN: A prospective study of 421 healthy children aged 7-9 years in 2001 who returned for follow-up in 2006. At both visits, retinal photographs and anthropometric measurements were taken following standardized protocols. Retinal arteriolar and venular calibers were measured using a computer-based program and summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). RESULTS: At follow-up, mean weight, height, and BMI increased significantly (P < .001). Mean CRVE increased by 3.4 µm (P < .001) but mean CRAE did not alter significantly (P = .340). On multivariate analysis, greater BMI was cross-sectionally associated with narrower CRAE (P < .01) and wider CRVE (P < .01). On longitudinal analysis, increasing BMI was associated with increasing CRVE (P = .04) over the 5-year period. Baseline BMI was associated with increased venular caliber and decreased arteriolar caliber at follow-up, and vice versa (P < .05). CONCLUSIONS: Increasing BMI is associated with increasing retinal venular caliber over time in children, and baseline retinal vascular caliber changes increase the risk of higher BMI at follow-up. As both widened retinal venular caliber and greater BMI are associated with risk of cardiovascular events in adults, progressive retinal venular widening could be a manifestation of an adverse microvascular effect of obesity early in life.