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Objective: To compare the vessel geometry characteristics of color fundus photographs in normal control and diabetes mellitus (DM) patients and to find potential biomarkers for early diabetic retinopathy (DR) based on a neural network vessel segmentation system and automated vascular geometry parameter analysis software. Methods: A total of 102 consecutive patients with type 2 DM (T2DM) and 132 healthy controls were recruited. All participants underwent general ophthalmic examinations, and retinal fundus photographs were taken with a digital fundus camera without mydriasis. Color fundus photographs were input into a dense-block generative adversarial network (D-GAN)-assisted retinal vascular segmentation system ( http://www.gdcerc.cn:8081/#/login ) to obtain binary images. These images were then analyzed by customized software (ocular microvascular analysis system V2.9.1) for automatic processing of vessel geometry parameters, including the monofractal dimension ( Dbox), multifractal dimension ( D0), vessel area ratio ( R), max vessel diameter ( dmax), average vessel diameter ( dave), arc–chord ratio (A/C), and tortuosity (τn). Geometric differences between the healthy subjects and DM patients were analyzed. Then, regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic efficiency of the vascular geometry parameters. Results: No significant differences were observed between the baseline characteristics of each group. DM patients had lower Dbox and D0 values (1.330 ± 0.041; 1.347 ± 0.038) than healthy subjects (1.343 ± 0.048, p < 0.05; 1.362 ± 0.042, p < 0.05) and showed increasing values of dmax, dave, A/C, and τn compared with normal controls, although only the differences in dave and τn between the groups were statistically significant. In the regression analysis, dave and τn showed a good correlation with diabetes ( dave, OR 1.765, 95% CI 1.319–2.362, p < 0.001; τn, OR 9.323, 95% CI 1.492–58.262, p < 0.05). Conclusions: We demonstrated the relationship between retinal vascular geometry and the process in DM patients, showing that Dbox, D0, dave, and τn may be indicators of morphological changes in retinal vessels in DM patients and can be early biomarkers of DR.

Purpose The vascular space occupancy (VASO) is a functional MRI technique for probing cerebral blood volume changes noninvasively, including during neuronal activation in humans. An important consideration when implementing VASO is the BOLD effect in the signal. Assessing the physical origin of this BOLD contamination and the capabilities of correction methods could improve the quantification of cerebral blood volume changes with VASO. Methods Given the heterogeneity of cerebral microvascular architecture, the vascular geometry within an MRI voxel can influence both BOLD and VASO signals. To investigate this effect, 3D high-resolution images of mouse cerebral vasculature measured with two-photon microscopy were used to model BOLD and VASO signals from first principles using Monte Carlo diffusion of water protons. Quantitative plots of VASO together with intravascular and extravascular BOLD signals as a function of TE at B0 fields 1.5 T to 14 T were obtained. Results The BOLD contamination of the VASO response was on the order of 50% for gradient echo and 5% for spin echo at 7 T and TE = 6 ms and significantly increased with TE and B0 . Two currently used correction schemes were shown to account for most of this contamination and recover accurate relative signal changes, with optimal correction obtained using TEs as short as possible. Conclusion These results may provide useful information for optimizing sequence parameters in VASO and BOLD functional MRI, leading the way to a wider application of these techniques in healthy and diseased brain.

The change in vascular geometry is an indicator of various health issues linked with vision and cardiovascular risk factors. Early detection and diagnosis of these changes can help patients to select an appropriate treatment option when the disease is in its primary phase. Automatic segmentation and quantification of these vessels would decrease the cost and eliminate inconsistency related to manual grading. However, automatic detection of the vessels is challenging in the presence of retinal pathologies and non-uniform illumination, two common occurrences in clinical settings. This paper presents a novel framework to address the issue of retinal blood vessel detection and width measurement under these challenging circumstances and also on two different imaging modalities: color fundus imaging and Scanning Laser Ophthalmoscopy (SLO). In this framework, initially, vessel enhancement is done using linear recursive filtering. Then, a unique combination of morphological operations, background estimation, and iterative thresholding are applied to segment the blood vessels. Further, vessel diameter is estimated in two steps: firstly, vessel centerlines are extracted using the graph-based algorithm. Then, vessel edges are localized from the image profiles, by utilizing spline fitting to obtain vascular orientations and then finding the zero-crossings. Extensive experiments have been carried out on several publicly accessible datasets for vessel segmentation and diameter measurement, i.e., DRIVE, STARE, IOSTAR, RC-SLO and REVIEW dataset. Results demonstrate the competitive and comparable performance than earlier methods. The encouraging quantitative and visual performance of the proposed framework makes it an important component of a decision support system for retinal images.

OBJECTIVEThe exact pathophysiological mechanisms underlying cerebral aneurysm formation remain unclear. Asymmetrical local vascular geometry may play a role in aneurysm formation and progression. The object of this study was to investigate the association between the geometric asymmetry of the middle cerebral artery (MCA) and the presence of MCA aneurysms and associated high-risk features.METHODSUsing a retrospective case-control study design, the authors examined MCA anatomy in all patients who had been diagnosed with an MCA aneurysm in the period from 2008 to 2017 at the University Hospitals Cleveland Medical Center. Geometric features of the MCA ipsilateral to MCA aneurysms were compared with those of the unaffected contralateral side (secondary control group). Then, MCA geometry was compared between patients with MCA aneurysms and patients who had undergone CTA for suspected vascular pathology but were ultimately found to have normal intracranial vasculature (primary control group). Parent vessel and aneurysm morphological parameters were measured, calculated, and compared between case and control groups. Associations between geometric parameters and high-risk aneurysm features were identified.RESULTSThe authors included 247 patients (158 cases and 89 controls) in the study. The aneurysm study group consisted of significantly more women and smokers than the primary control group. Patients with MCA bifurcation aneurysms had lower parent artery inflow angles (p = 0.01), lower parent artery tortuosity (p < 0.01), longer parent artery total length (p = 0.03), and a significantly greater length difference between ipsilateral and contralateral prebifurcation MCAs (p < 0.01) than those in primary controls. Type 2 MCA aneurysms (n = 89) were more likely to be associated with dome irregularity or a daughter sac and were more likely to have a higher cumulative total of high-risk features than type 1 MCA aneurysms (n = 69).CONCLUSIONSData in this study demonstrated that a greater degree of parent artery asymmetry for MCA aneurysms is associated with high-risk features. The authors also found that the presence of a long and less tortuous parent artery upstream of an MCA aneurysm is a common phenotype that is associated with a higher risk profile. The aneurysm parameters are easily measurable and are novel radiographic biomarkers for aneurysm risk assessment.

Background We aimed to examine the cross-sectional association between a range of retinal vascular geometric variables and the prevalence of atrial fibrillation (AF) and heart failure. Methods The Australian Heart Eye Study (AHES) surveyed 1,680 participants presenting to a tertiary referral hospital for the evaluation of potential coronary artery disease by coronary angiography. Retinal vascular geometric variables (tortuosity, branching, and fractal dimension) were measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Atrial fibrillation was determined based on a combination of: self-reported history of AF; self-reported use of rate-control and anti-arrhythmic medications; and/or screening electrocardiogram. Self-reported echocardiography-confirmed heart failure was also documented. Results A total of 1,169 participants had complete information on retinal vascular geometric variables and AF and of these 104 (8.9%) had AF. Participants in the second tertile of fractal dimension (Df) compared to those in the highest tertile (reference group), had 92% increased likelihood of having AF after multivariable adjustment. A threshold effect for Df was identified, and participants below versus those above a Df threshold value of 1.472, had greater odds of having AF: multivariable-adjusted OR 1.85 (95% CI 1.03–3.31). Measures of retinal tortuosity and branching were not associated with AF. Retinal vascular geometric variables were also not associated with prevalence of heart failure. Conclusions A sparser retinal microvascular network (lower Df) was independently associated with greater likelihood of AF. Further studies are needed to investigate whether temporal changes to the retinal vascular geometry are predictive of AF in the longer term.

With an increasingly elderly population globally, the impacts of cerebrovascular diseases, such as stroke and dementia, become increasingly significant. Haemorrhagic transformation (HT) is one of the most common complications of ischaemic stroke that is caused by dysfunction of endothelial cells in the blood-brain barrier (BBB) and that can be exacerbated by thrombolytic therapy. Recent studies also suggest that HT can lead to an increase in intracranial pressure (ICP) and result in capillary compression. The aim of this study is to develop a mathematical model that can be used to simulate the consequence of HT over a range of vasculature length scales. We use a 2D vasculature model to investigate the severity of HT with different vascular geometry. The resulting model shows that the haematoma radius is approximately constant across different length scales (100-1000μm) and in good agreement with the available experimental data. In addition, this study identified that the effects of capillary compression do appear to have a significant impact on the leakage fraction of blood and hence act to restrain the development of a haematoma.

Atherosclerosis in different vascular locations leads to distinct clinical consequences, such as ischemic stroke and myocardial infarction. Genome-wide association studies in humans revealed that genetic loci responsible for carotid plaque and coronary artery disease were not overlapping, suggesting that distinct genetic pathways might be involved for each location. While elevated plasma cholesterol is a common risk factor, plaque development in different vascular beds is influenced by hemodynamics and intrinsic vascular integrity. Despite the limitation of species differences, mouse models provide platforms for unbiased genetic approaches. Mouse strain differences also indicate that susceptibility to atherosclerosis varies, depending on vascular locations, and that the location specificity is genetically controlled. Quantitative trait loci analyses in mice suggested candidate genes, including Mertk and Stab2, although how each gene affects the location-specific atherosclerosis needs further elucidation. Another unbiased approach of single-cell transcriptome analyses revealed the presence of a small subpopulation of vascular smooth muscle cells (VSMCs), which are “hyper-responsive” to inflammatory stimuli. These cells are likely the previously-reported Sca1+ progenitor cells, which can differentiate into multiple lineages in plaques. Further spatiotemporal analyses of the progenitor cells are necessary, since their distribution pattern might be associated with the location-dependent plaque development.

Hemodynamic stress is thought to play an important role in the formation of intracranial aneurysms, which is conditioned by the geometry of the surrounding vasculature. Our goal was to identify image-based morphological parameters that were associated with basilar artery tip aneurysms (BTA) in a location-specific manner. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 207 patients with BTAs and a control group of 106 patients with aneurysms elsewhere to control for non-morphological factors, who were diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. We examined the presence of hypoplastic, aplastic or fetal PCoAs, vertebral dominance, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In multivariable analysis, daughter–daughter angle was directly, and parent artery diameter and diameter size ratio were inversely associated with BTAs. These results remained significant in the subgroup analysis of small aneurysms (width ≤ 3 mm) and when angles were excluded. These easily measurable and robust parameters that are unlikely to be affected by aneurysm formation could aid in risk stratification for the formation of BTAs in high-risk patients.

Background Three-dimensional (3D) printing has revolutionized training, education, and device testing. Understanding the design and physical properties of 3D-printed models is important. Objective To systematically review the design, physical properties, accuracy, and experimental outcomes of 3D-printed vascular models used in neurointervention. Methods We conducted a systematic review of the literature between January 1, 2000 and September 30, 2018. Public/Publisher MEDLINE (PubMed), Web of Science, Compendex, Cochrane, and Inspec databases were searched using Medical Subject Heading terms for design and physical attributes of 3D-printed models for neurointervention. Information on design and physical properties like compliance, lubricity, flow system, accuracy, and outcome measures were collected. Results A total of 23 articles were included. Nine studies described 3D-printed models for stroke intervention. Tango Plus (Stratasys) was the most common material used to develop these models. Four studies described a population-representative geometry model. All other studies reported patient-specific vascular geometry. Eight studies reported complete reconstruction of the circle of Willis, anterior, and posterior circulation. Four studies reported a model with extracranial vasculature. One prototype study reported compliance and lubricity. Reported circulation systems included manual flushing, programmable pistons, peristaltic, and pulsatile pumps. Outcomes included thrombolysis in cerebral infarction, post-thrombectomy flow restoration, surgical performance, and qualitative feedback. Conclusion Variations exist in the material, design, and extent of reconstruction of vasculature of 3D-printed models. There is a need for objective characterization of 3D-printed vascular models. We propose the development of population representative 3D-printed models for skill improvement or device testing.

Hemodynamic changes occurring at the segments of arterial bifurcations, up and down stream of stenotic vessels appear to play a critical role in the development of atherosclerosis. Therefore, we hypothesized that basilar artery (BA) geometry may be related to the distribution of atherosclerotic plaque. In this retrospective cross-sectional study, all patients hospitalized with ischemic stroke and intracranial atherosclerotic disease were sifted from March 2017 to October 2017. Sixty-seven patients with intracranial atherosclerotic disease (39 with and 28 without BA atherosclerosis) were analyzed. Magnetic resonance imaging, magnetic resonance angiography, and high-resolution black-blood MRI were performed within 7 days after symptoms onset. BA tortuosity, plaque location, and plaque enhancement were assessed. Plaque burden and vascular remodeling were measured. Of the 39 patients with BA atherosclerosis, plaques preferred to be formed at the inner arc than the outer arc (27/39, 69% vs 12/39, 31%) in the tortuous BA. In addition, patients with BA plaque had a greater vascular tortuosity compared with those without plaque (113.1 ± 10.2 vs 107 ± 4.6; P = .034). Finally, patients with apparent BA plaque had greater plaque enhancement (14/21, 67% vs 5/18, 28%; P = .017) and plaque burden (0.76 ± 0.15 vs 0.70 ± 0.09; P = .036) compared with those with minimal plaque. Plaque may be more likely to form at the inner arc of tortuous BA with atherosclerotic disease, and increased BA tortuosity is associated with its likelihood to form plaque.

Arterial hemodynamics is markedly characterized by the presence of helical flow patterns. Previous observations suggest that arterial helical blood flow is of physiological significance, and that its quantitative analysis holds promise for clinical applications. In particular, it has been reported that distinguishable helical flow patterns are potentially atheroprotective in the carotid bifurcation as they suppress flow disturbances. In this context, there is a knowledge gap about the physiological significance of helical flow in coronary arteries, a prominent site of atherosclerotic plaque formation. This study aimed at the quantitative assessment of helical blood flow in coronary arteries, and to investigate its possible associations with vascular geometry and with atherogenic wall shear stress (WSS) phenotypes in a representative sample of 30 swine coronary arteries. This study demonstrates that in coronary arteries: (1) the hemodynamics is characterized by counter-rotating bi-helical flow structures; (2) unfavorable conditions of WSS are strongly and inversely associated with helicity intensity (r = − 0.91; p

Background Retinal arteriolar narrowing and venular widening has been widely suggested to be associated with subclinical changes in cardiac structure. The novel retinal vascular geometric indices might reflect more comprehensive information on microvasculature other than vascular caliber alone. However, the association between suboptimal retinal vascular geometry and cardiac structural alteration has not been studied. Methods and Results We recruited 50 participants without cardiovascular disease from the Cardiac Aging Study conducted between 2014 and 2016. We performed transthoracic echocardiography imaging to measure cardiac structure indices such as left ventricular internal diameter end diastole index, left ventricular internal diameter end systole index, left ventricular mass index, and left atrial volume index, and retinal imaging to measure retinal vascular geometric indices including branching angle, curvature tortuosity, and fractal dimension. We applied multiple linear regressions to examine associations between indices of cardiac structure and retinal vascular geometry, adjusting for age, sex, body mass index, mean blood pressure, and comorbidity. The average age of all participants was 62.54 years old and slightly more than half were male (27; 54%). Each unit increase in a set of cardiac structure indices was associated with larger retinal arteriolar branching angle (β and 95% CI : for left ventricular internal diameter end systole index, 26.93°; 6.00–47.86; for left ventricular internal diameter end diastole index, 17.86°; 1.61–34.11; for left ventricular mass index, 0.39°; 0.10–0.67; for left atrial volume index, 0.91°; 0.24–1.58). Conclusions Adverse retinal arteriolar geometric morphology mirrored suboptimal cardiac structural alteration.

Accurate vascular geometry modeling is an essential task in computer assisted vascular surgery and therapy. This paper presents a vessel cross-section based implicit vascular modeling technique, which represents a vascular surface as a set of locally fitted implicit surfaces. In the proposed method, a cross-section based technique is employed to extract from each cross-section of the vascular surface a set of points, which are then fitted with an implicit curve represented as 2D radial basis functions. All these implicitly represented cross-section curves are then being considered as 3D cylindrical objects and combined together using a certain partial shape-preserving spline to build a complete vessel branch; different vessel branches are then blended using a extended smooth maximum function to construct the complete vascular tree. Experimental results show that the proposed method can correctly represent the morphology and topology of vascular structures with high level of smoothness. Both qualitative comparison with other methods and quantitative validations to the proposed method have been performed to verify the accuracy and smoothness of the generated vascular geometric models.

BACKGROUND AND PURPOSE Subclinical atherosclerotic plaques are common in patients with pontine infarctions (PIs) but without basilar artery (BA) stenosis. We hypothesized that BA plaque locations may differ by PI type and vertical location as well as vertebrobasilar artery geometry. METHODS Ninety-six patients with PI but without BA stenosis on magnetic resonance imaging (MRI) and magnetic resonance angiography were enrolled. PIs were classified by type (paramedian, deep, or lateral) and vertical location (rostral, middle, or caudal). Patients underwent high-resolution MRI to evaluate BA plaque location (anterior, posterior, or lateral). The mid-BA angle on anteroposterior view and angle between the BA and dominant vertebral artery (BA-VA angle) on lateral view were measured. RESULTS The PIs were paramedian (72.9%), deep (17.7%), and lateral (9.4%) type with a rostral (32.3%), middle (42.7%), and caudal (25.0%) vertical location. The BA plaque locations differed by PI type (P=0.03) and vertical location (P

Segmentation of vasculature specific to the patients’ carotid vasculature is a complicated and challenging task because of its complex geometrical structure and interconnections. Accurate or approximate digital phantoms of the vasculature are extremely useful in quick analysis of the vascular geometry and the modelling of blood flow in the cerebrovasculature. All these analyses lead to effective diagnosis and detection/localization of the diseased arterial segment in the cerebrovasculature. In this work, we have proposed a semiautomatic geodesic path propagation algorithm based on fuzzy distance transform to generate digital cerebrovascular phantoms from the patients’ CT angiogram (CTA) images. We have also custom-developed a 2-D/3-D user interface for accurate placement of user-specified seeds on the input images. The proposed method effectively separates the artery/vein regions from the soft bones in the overlapping intensity regions using minimal human interaction. Qualitative results along with 3-D rendition of the segmented cerebrovasculature on eight patients’ CTA images are presented here.

Optical Coherence Tomography Angiography (OCTA) is a novel, non-invasive imaging modality of retinal capillaries at micron resolution. While OCTA generates 3D image volumes, current analytic methods rely on 2Den faceprojection images for quantitative analysis. This obscures the 3D vascular geometry and prevents accurate characterization of retinal vessel networks. In this paper, we have developed an automated analysis framework that preserves the 3D geometry of OCTA data. This framework uses curvelet-based denoising, optimally oriented flux (OOF) vessel enhancement and projection artifact removal, as well as the generation of 3D vessel length from the Hamilton-Jacobi skeleton. We implement this method on a dataset of 338 OCTA scans from human subjects with diabetic retinopathy (DR) which is known to cause decrease in capillary density and compare them to healthy controls. Our results indicate that 3D vessel-skeleton-length (3D-VSL) captures differences in both superficial and deep capillary density that are not apparent in 2D vessel skeleton analyses. In statistical analysis, we show that the 3D small-vessel-skeleton-length (3D-SVSL), which is computed after the removal of the large vessels and associated projection artifacts, provides a novel metric to detect group differences between healthy controls and progressive stages of DR.This work was supported in part by NIH grants UH3NS100614, R21EY027879, U01EY025864, K08EY027006, P41EB015922, P30EY029220, Research to Prevent Blindness, and UL1TR001855 and UL1TR000130 from the National Center for Advancing Translational Science (NCATS) of the U.S. National Institutes of Health.

In order to grasp the spatial and temporal evolution of vascular geometry, three-dimensional (3D) arterial bending structure and geometrical changes of arteries and stent grafts (SG) must be quantified using geometrical parameters such as curvature and torsion along the vasculature centerlines extracted from medical images. Here, we develop a robust method for constructing smooth centerlines based on a spline fitting method (SFM) such that the optimized geometric parameters of curvature and torsion can be obtained independently of digitization noise in the images. Conventional SFM consists of the 3rd degree spline basis function and 2nd derivative penalty term. In contrast, the present SFM uses the 5th degree spline basis function and 3rd and 4th derivative penalty terms, the coefficients of which are derived by the Akaike information criterion. The results show that the developed SFM can reduce the errors of curvature and torsion compared to conventional SFM. We then apply the present SFM to the centerline of the SG in an abdominal aortic aneurysm (AAA), and those of bilateral internal carotid arteries (ICA) in 6 cases: 3 cases with aneurysms and 3 cases without any aneurysm. The SG centerlines were obtained from temporal medical images at three scan times. The strong peak of the curvature could be clearly observed in the distal area of the SG, the inversion of the torsion at 0 months in the middle area of SG disappeared over time, and the torsions around the SG bifurcation at the three time periods were inverted. The curvature-torsion graphs along the ICA centerlines superimposing five aneurysmal positions were useful for investigating the relationship between arterial bending structure and aneurysmal positions. Both ICAs had curvature peak values higher than 0.4 within the ICA syphons. The ICA torsion graphs indicated that left and right ICA tended to be a right- and left-handed helix, respectively. In the left ICA syphon, the biggest aneurysm could be observed downstream of the salient torsion inversion. All aneurysms for 3 cases were positioned at the downstream of the inverted torsion.

Flow diversion is increasingly used for treating intracranial aneurysms. This article aims to review the evidence obtained from animal models and summarizes the findings that might be of clinical interest. From a systematic review of studies published between 2000 and 2016, we extracted the data on the following questions: What roles do aneurysm dimension, morphology, and vascular geometry have on success of flow diversion? What characteristics of a flow diverter can influence aneurysm occlusion? What are the risk factors for jailed branch occlusion? Flow diversion has been shown to be less effective in occluding large aneurysms with wide or undefined necks, as compared to smaller aneurysms with narrower necks. Straight sidewall aneurysms were more likely to occlude after flow diversion than curved sidewall aneurysms or bifurcation aneurysms with branches originating from the neck or the fundus. The main characteristics of devices that may impact on the success of flow diversion are porosity and pore-density, but challenging aneurysm models were not better occluded with devices of lower porosity. Porosity is not uniform when devices deform to adapt to local in vivo anatomy when deployed. Neointima formation on devices correlates with low porosity. Branches are rarely occluded when they are jailed, but persistent branch flow may prevent aneurysm occlusion. Experimental models may help anticipate clinical results of flow diversion.

Background and Purpose— Hemodynamic forces may play a role in the recanalization of coiled aneurysms. The purpose of this study was to investigate the influence of presurgical hemodynamics on the efficacy of coil embolization for basilar tip aneurysms. Methods— We identified 82 patients who underwent endovascular coil embolization for basilar tip aneurysms with a follow-up of >1 year. Presurgical hemodynamics were investigated using computational fluid dynamics with 3-dimensional data derived from rotational angiography. During postprocessing, we quantified the rate of net flow entering the aneurysm through its neck and calculated the proportion of the aneurysmal inflow rate to the basilar artery flow rate. In addition, we investigated the correlation between the basilar bifurcation configuration and the hemodynamics. Results— Twenty-five of the 82 patients were excluded because of difficult vascular geometry reconstruction. Among the 57 examined patients, angiographic recanalization was observed in 19 patients (33.3%). The proportion of the aneurysmal inflow rate to the basilar artery flow rate and a coil packing density Conclusions— The proportion of the aneurysmal inflow rate to the basilar artery flow rate, influenced by the basilar bifurcation configuration, was an independent and significant predictor for recanalization after coil embolization in basilar tip aneurysms.

Recent studies have supported the hypothesis that exposure to established cardiovascular risk factors in early life predisposes to the development of adult cardiovascular disease. Retinal imaging is an emerging technique which facilitates non-invasive, accurate and reproducible assessment of the retinal microvasculature. The assessment may be in the form of static vascular calibre measurements and assessment of the vascular geometry or dynamic structural and functional assessments. Paediatric retinal microvascular changes are reported in response to elevated blood pressure, type 1 diabetes, increasing adiposity, diet, physical activity, systemic inflammation, metabolic peptides, family history and prenatal factors. The resultant microvascular changes have been linked to sub-clinical and overt cardiovascular, cerebrovascular and metabolic disease states in the adult population. Still missing however is longitudinal evidence showing the persistence of retinal microvascular alterations into adulthood. Future studies will enable retinal microvascular assessment to further evaluate the pathogenesis of disease states and response to intervention. The data obtained will also aid in expanding the clinical utility of retinal imaging as a cardiovascular risk prediction and monitoring tool and supplement existing recommendations to reduce cardiovascular morbidity and mortality.

Background and Objective: Intra-operative X-ray angiography, the current standard method for visualizing and diagnosing cardiovascular disease, is limited in its ability to provide essential 3D information. These limitations are disadvantages in treating patients. For example, it is a cause of lowering the success rate of interventional procedures. Here, we propose a novel 2D-3D non-rigid registration method to understand vascular geometry during percutaneous coronary intervention. Methods: The proposed method uses the local bijection pair distance as a cost function to minimize the effect of inconsistencies from center-line extraction. Moreover, novel cage-based 3D deformation and multi-threaded particle swarm optimization are utilized to implement real-time registration. We evaluated the proposed method for 154 examinations from 10 anonymous patients by coverage percentage, comparing the average distance of the 2D extracted center-line with that of the registered 3D center-line. Results: The proposed 2D-3D non-rigid registration method achieved an average distance of 1.98 mm with a 0.54 s computation time. Additionally, in aiming to reduce the uncertainty of XA images, we used the proposed method to retrospectively visualize the connections between 2D vascular segments and the distal part of occlusions. Conclusions: Ultimately, the proposed 2D/3D non-rigid registration method can successfully register the 3D center-line of coronary arteries with corresponding 2D XA images, and is computationally sufficient for online usage. Therefore, this method can improve the success rate of such procedures as a percutaneous coronary intervention and provide the information necessary to diagnose cardiovascular diseases better.

Aim: Development of atherosclerotic plaques is affected by vascular geometry and hemodynamics. Hemodynamics in the basilar artery (BA) is unique as the flow converges from vertebral arteries (VAs). Here, we investigated the characteristics of BA plaque based on VA and BA geometry. Methods: Consecutive patients evaluated using high-resolution magnetic resonance imaging (MRI) at a general health center were screened. Geometric characteristics of VA (VA dominancy and VA-BA angles) and BA (BA convexity and BA angles) were assessed. The burden of BA plaques was investigated in each wall (anterior, posterior, left, and right lateral). The characteristics of BA plaques were compared according to VA dominancy (right vs. left), BA angle of lateral view (lateral mid-BA angle; dichotomized), and total plaque burden (divided by tertiles). Results: Of the 1029 subjects, BA plaques were observed in 98 (9.5%) patients, and were more frequently located at the anterior wall (32.4%) and posterior wall (35.0%) than the right wall (15.3%) and left lateral wall (17.6%). Right and left lateral plaques were more frequent in the left and right convex BA, respectively (p = 0.009 and p = 0.024, respectively). Anterior plaques were more frequently observed in low lateral mid-BA angle (p = 0.043). BA plaques were predominant in anterior and posterior walls in patients with lower plaque burden, whereas they were predominant in right and left lateral walls in patients with higher plaque burden (p = 0.001 and p = 0.025, respectively). Conclusions: Asymptomatic BA plaque location was associated with BA convexity and lateral mid-BA angle. The anteriorly and posteriorly located BA plaques may extend to the lateral walls as the plaque burden increases.

The vascular space occupancy (VASO) fMRI method probes changes in cerebral blood volume (CBV) under various physiological states, including neuronal activation in humans. However, it requires a careful choice of sequence parameters because the blood oxygen-level dependent (BOLD) effect offsets the VASO signal. Assessing this BOLD contamination as a function of pulse sequence parameters would improve the quantification of CBV changes with VASO. However, this task requires knowledge of the cerebral vascular geometry of the MRI voxel. Towards this end, optical microscopy can provide high-resolution 3D images of vasculature. Here, we use detailed angiograms of rodent brain acquired with two-photon microscopy to model fMRI signals (VASO and BOLD) from first principles using Monte Carlo diffusion of water protons. We present quantitative plots of VASO together with intra- and extravascular BOLD fractional signal changes as a function of echo time (TE), for spin echo (SE) and gradient echo (GRE) pulse sequences, at low to ultra-high magnetic fields. Our results indicate that at 3T, the BOLD contamination of the VASO response is under 12% for GRE and 2% for SE up to TE=6 ms, but this contamination is significantly higher at 7T and above. We also found GRE BOLD intravascular contributions of 85% at 1.5T, 55% at 3T and 4% at 7T and SE intravascular contributions of 70% at 1.5T, 40% at 3T and 10% at 7T. These results may provide important information to optimize the pulse sequence timing in human VASO and BOLD fMRI, leading the way to a wider application of these fMRI techniques in healthy and diseased brain.

This study is to establish quantitative features of vascular geometry in optical coherence tomography angiography (OCTA) and validate them for the objective classification of diabetic retinopathy (DR). Six geometric features, including total vessel branching angle (VBA: θ), child branching angles (CBAs: α1 and α2), vessel branching coefficient (VBC), and children-to-parent vessel width ratios (VWR1 and VWR2), were automatically derived from each vessel branch in OCTA. Comparative analysis of heathy control, diabetes with no DR (NoDR), and non-proliferative DR (NPDR) was conducted. Our study reveals four quantitative OCTA features to produce robust DR detection and staging classification: (ANOVA, P

International audience; Today, additive manufacturing (AM) is implemented in medical industry and profoundly revolutionizes this area. This approach consists of producing parts by additions of layers of successive materials and offers advantages in terms of rapidity, complexity of parts, competitive costs that can be exploited and can lead to a significant advancement in biological research. Everything becomes technically feasible and gives way to a “techno-centered” approach. Many parameters must be controlled in this field, so it is necessary to be guided for the development of such a product. This article aims to present a state of the art of existing design methodologies focused on AM to create medical devices. Finally, a development method is proposed that consists of producing vascular geometry using AM, based on patient data, designed for cell culture in vitro studies.

Introduction Intra-aneurysmal flow is influenced by the curvature of the parent artery. Stent placement may straighten parent vessels with an impact in local hemodynamics. Few data have been reported about vascular geometry modification with the use of flow-diverter stents (FDS). The purpose of this study was to evaluate the geometry changes due to FDs placement in distal arteries and to compare nitinol and cobalt-chromium FDs angle modifications. Methods We included patients treated with FDS for distal aneurysm between January 2012 and January 2018. Angles at the level of the neck have been measured on pre- and post-operative DSA in working projections. Angles measurement was performed at the intersection of 2 lines drawn from the neck center in the axis of the proximal and distal segments of the parent artery (figure 1). Angles variation was quantified with a rectification coefficient (R coeff)=(beta-alpha)/beta with alpha and beta respectively angles before and after FDS placement. Results 38 patients have been included. 5 (13%) received a nitinol FDS and 33 (87%) a cobalt-chromium FDS. The mean pre-operative and post-operative angles were respectively 107,2° and 133,6° (p Conclusion FDs placement for distal aneurysms modulates vascular anatomy and might influence flow modifications and occlusion rates. This appears to be more important with cobalt-chromium than with nitinol FDS. Disclosures K. Janot: None. V. Espindola: None. S. Saleme: None. A. El Ghanam: None. L. Mattos: None. C. Mounayer: None. A. Rouchaud: None.

Placental function is essential for the development of the fetus, and is – in part – related to the 3D arrangement of the villous and vascular geometry. Recent advances in tissue clarification techniques allow for deep high-resolution imaging with confocal microscopy without altering the spatial characteristics of the tissue. These image stacks can be analyzed quantitatively to provide insights regarding the villous and vascular micro-anatomy as well as the interrelationships between the two. However, such analyses require optimization of the tissue preparation, immuno-labeling, and clarification protocol in order to provide reliable results suitable for the detection of subtle differences in pathologic pregnancies. Placental and fetal development are similar between human and non-human primate pregnancies, with the latter serving as a reliable, validated, highly-controlled, well-characterized translational model for the former.We present a protocol for the preparation, immuno-labeling, and clarification of the non-human primate placenta optimized for confocal microscopy and subsequent quantification of the micro-anatomic structures.

Aberrant flow conditions are implicated in aneurysmal growth or rupture. Current approaches that analyze the effects of flow stress on vascular cells are limited by their simplistic design, lacking patient-specific vascular anatomic features that contribute to disease. Computational fluid dynamics (CFD) is commonly used to characterize the biophysical properties of patient-specific anatomy but neglects the biologic interface between the blood stream and the endothelial surface. The purpose of this study is to develop a new research model for analyzing gene expression influenced by complex-flow stress on endothelial cells using a precision medicine approach that incorporates three-dimensional (3D) patient-specific vascular geometry. Hollow vessel models were created with silicone using 3D printing technology from image data obtained by routine MRA, CTA or rotational angiography obtained in normal clinical practice. The vessel models coated with fibronectin were rotated in 3D with endothelium in culture incubator for cell lining. CFD study was performed to characterize the flow dynamics with specific regions of the vessel models. Viscosity-adjusted culture media was perfused using perfusion conditions calculated by CFD in the circulation with the endothelialized vascular model. After perfusion, RNA was extracted from endothelial cells in the parent artery and the aneurysm and gene expression was examined using quantitative PCR (qPCR). In addition, the morphology of endothelial cells in specific regions of the model were observed with confocal microscopy. Endothelial cells in regions of low wall shear and oscillatory flow within the aneurysm were irregular in shape and size and associated with up-regulation of inflammatory genes compared with cells in the parent artery that exhibited typical spindle shape and aligned with the directionality of flow. This novel in vitro model enables a new research approach to bridge the gap of biophysical flow phenomonology and the biological impact of complex flow patterns on endothelial cells using patient-derived imaging data. Such models are likely to be useful to determine flow-driven biologic changes in vascular endothelium that contribute to aneurysmal growth and rupture.

Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis. Vascular smooth muscle cells (VSMCs) were cyclically stretched on flexible membranes, as quantified via video tracking, demonstrating that the expression of Jagged1, Notch3, and target genes was down-regulated with strain. The data were incorporated in a computational framework of Notch signaling in the vascular wall, where the mechanical load was defined by the vascular geometry and blood pressure. Upon increasing wall thickness, the model predicted a switch-type behavior of the Notch signaling state with a steep transition of synthetic toward contractile VSMCs at a certain transition thickness. These thicknesses varied per investigated arterial location and were in good agreement with human anatomical data, thereby suggesting that the Notch response to hemodynamics plays an important role in the establishment of vascular homeostasis., Proceedings of the National Academy of Sciences of the United States of America, 115 (16), ISSN:0027-8424, ISSN:1091-6490

Objective Native arteriovenous fistulas (AVFs) for hemodialysis are susceptible to nonmaturation. Adverse features of local blood flow have been implicated in the formation of perianastomotic neointimal hyperplasia that may underpin nonmaturation. Whereas computational fluid dynamic simulations of idealized models highlight the importance of geometry on fluid and vessel wall interactions, little is known in vivo about AVF geometry and its role in adverse clinical outcomes. This study set out to examine the three-dimensional geometry of native AVFs and the geometric correlates of AVF failure. Methods As part of an observational study between 2013 and 2016, patients underwent creation of an upper limb AVF according to current surgical best practice. Phase-contrast magnetic resonance imaging was performed on the day of surgery to obtain luminal geometry along with ultrasound measurements of flow. Magnetic resonance imaging data sets were segmented and reconstructed for quantitative and qualitative analysis of local geometry. Clinical maturation was evaluated at 6 weeks. Results There were 60 patients who were successfully imaged on the day of surgery. Radiocephalic (n = 17), brachiocephalic (n = 40), and brachiobasilic (n = 3) fistulas were included in the study. Centerlines extracted from segmented vessel lumen exhibited significant heterogeneity in arterial nonplanarity and curvature. Furthermore, these features are more marked in brachiocephalic than in radiocephalic fistulas. Across the cohort, the projected bifurcation angle was 73 ± 16 degrees (mean ± standard deviation). Geometry was preserved at 2 weeks in 20 patients who underwent repeated imaging. A greater degree of arterial nonplanarity (log odds ratio [logOR], 0.95 per 0.1/vessel diameter; 95% confidence interval [CI], 0.22-1.90; P = .03) and a larger bifurcation angle (logOR, 0.05 per degree; 95% CI, 0.01-0.09; P = .02) are associated with a greater rate of maturation, as is fistula location (upper vs lower arm; logOR, −1.9; 95% CI, −3.2 to 0.7; P = .002). Conclusions There is significant heterogeneity in the three-dimensional geometry of AVFs, in particular, arterial nonplanarity and curvature. In this largest cohort of AVF geometry to date, the effect of individual geometric correlates on maturation is uncertain but supports the premise that future modeling studies will need to acknowledge the complex geometry of AVFs.

Normal aortic compliance allows cardiac output to be distributed throughout the cardiac cycle, resulting in lower peak blood velocity. Loss of compliance with aging, hypertension, and possibly other risk factors for atherosclerosis increases peak blood velocity, creating eddy currents in areas of changing vascular geometry, as well as creating adverse patterns of diastolic flow. In the resulting areas of low flow, increased blood viscosity creates the potential for thrombosis. Occlusive thrombi may cause death; parietal or mural thrombi may organize to form atherosclerotic plaques.

Introduction The fetoplacental vasculature network is essential for the exchange of nutrients, gases and wastes with the maternal circulation and for normal fetal development. The present study quantitatively compares arterial and venous morphological and functional differences in the mouse fetoplacental vascular network. Methods High resolution X-ray micro-computed tomography was used to visualize the 3D geometry of the arterial and venous fetoplacental vasculature in embryonic day 15.5 CD-1 mice (n = 5). Automated image analysis was used to measure the vascular geometry of the approximately 4100 arterial segments and 3200 venous segments per specimen to simulate blood flow through these networks. Results Both the arterial and venous trees demonstrated a hierarchical branching structure with 8 or 9 (arterial) or 8 (venous) orders. The venous tree was smaller in volume and overall dimensions than the arterial tree. Venous vessel diameters increased more rapidly than arteries with each successive order, leading to lower overall resistance, although the umbilical vein was notably smaller and of higher resistance than these scaling relationships would predict. Simulation of blood flow for these vascular networks showed that 57% of total resistance resides in the umbilical artery and arterial tree, 17% in the capillary bed, and 26% in the venous tree and umbilical vein. Discussion A detailed examination of the mouse fetoplacental arterial and venous tree revealed features, such as the distribution of resistance and the dimension of the venous tree, that were both morphologically distinct from other vascular beds and that appeared adapted to the specialized requirements of sustaining a fetus.