Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Elastic Registration of Geodesic Vascular Graphs

Vascular graphs can embed a number of high-level features, from morphological parameters, to functional biomarkers, and represent an invaluable tool for longitudinal and cross-sectional clinical inference. This, however, is only feasible when graphs are co-registered together, allowing coherent multiple comparisons. The robust registration of vascular topologies stands therefore as key enabling technology for group-wise analyses. In this work, we present an end-to-end vascular graph registration approach, that aligns networks with non-linear geometries and topological deformations, by introducing a novel overconnected geodesic vascular graph formulation, and without enforcing any anatomical prior constraint. The 3D elastic graph registration is then performed with state-of-the-art graph matching methods used in computer vision. Promising results of vascular matching are found using graphs from synthetic and real angiographies. Observations and future designs are discussed towards potential clinical applications

Solid NURBS Conforming Scaffolding for Isogeometric Analysis

This work introduces a scaffolding framework to compactly parametrise solid structures with conforming NURBS elements for isogeometric analysis. A novel formulation introduces a topological, geometrical and parametric subdivision of the space in a minimal plurality of conforming vectorial elements. These determine a multi-compartmental scaffolding for arbitrary branching patterns. A solid smoothing paradigm is devised for the conforming scaffolding achieving higher than positional geometrical and parametric continuity. Results are shown for synthetic shapes of varying complexity, for modular CAD geometries, for branching structures from tessellated meshes and for organic biological structures from imaging data. Representative simulations demonstrate the validity of the introduced scaffolding framework with scalable performance and groundbreaking applications for isogeometric analysis

Large and Dense Swarms: Simulation of a Shortest Path Alarm Propagation

This paper deals with the transmission of alarm messages in large and dense underwater swarms of Autonomous Underwater Vehicles (AUVs) and describes the verification process of the derived algorithm results by means of two simulation tools realized by the authors. A collision-free communication protocol has been developed, tailored to a case where a single AUV needs to send a message to a specific subset of swarm members regarding a perceived danger. The protocol includes a handshaking procedure that creates a silence region before the transmission of the message obtained through specific acoustic tones out of the normal transmission frequencies or through optical signals. This region will include all members of the swarm involved in the alarm message and their neighbours, preventing collisions between them. The AUV sending messages to a target area computes a delay function on appropriate arcs and runs a Dijkstra-like algorithm obtaining a multicast tree. After an explanation of the whole building of this collision-free multicast tree, a simulation has been carried out assuming different scenarios relevant to swarm density, signal power of the modem and the geometrical configuration of the nodes

A comparative evaluation of 3 different free-form deformable image registration and contour propagation methods for head and neck MRI : the case of parotid changes radiotherapy

Purpose: To validate and compare the deformable image registration and parotid contour propagation process for head and neck magnetic resonance imaging in patients treated with radiotherapy using 3 different approachesthe commercial MIM, the open-source Elastix software, and an optimized version of it. Materials and Methods: Twelve patients with head and neck cancer previously treated with radiotherapy were considered. Deformable image registration and parotid contour propagation were evaluated by considering the magnetic resonance images acquired before and after the end of the treatment. Deformable image registration, based on free-form deformation method, and contour propagation available on MIM were compared to Elastix. Two different contour propagation approaches were implemented for Elastix software, a conventional one (DIR_Trx) and an optimized homemade version, based on mesh deformation (DIR_Mesh). The accuracy of these 3 approaches was estimated by comparing propagated to manual contours in terms of average symmetric distance, maximum symmetric distance, Dice similarity coefficient, sensitivity, and inclusiveness. Results: A good agreement was generally found between the manual contours and the propagated ones, without differences among the 3 methods; in few critical cases with complex deformations, DIR_Mesh proved to be more accurate, having the lowest values of average symmetric distance and maximum symmetric distance and the highest value of Dice similarity coefficient, although nonsignificant. The average propagation errors with respect to the reference contours are lower than the voxel diagonal (2 mm), and Dice similarity coefficient is around 0.8 for all 3 methods. Conclusion: The 3 free-form deformation approaches were not significantly different in terms of deformable image registration accuracy and can be safely adopted for the registration and parotid contour propagation during radiotherapy on magnetic resonance imaging. More optimized approaches (as DIR_Mesh) could be preferable for critical deformations

VTrails: Inferring Vessels with Geodesic Connectivity Trees

The analysis of vessel morphology and connectivity has an impact on a number of cardiovascular and neurovascular applications by providing patient-specific high-level quantitative features such as spatial location, direction and scale. In this paper we present an end-to-end approach to extract an acyclic vascular tree from angiographic data by solving a connectivity-enforcing anisotropic fast marching over a voxel-wise tensor field representing the orientation of the underlying vascular tree. The method is validated using synthetic and real vascular images. We compare VTrails against classical and state-of-the-art ridge detectors for tubular structures by assessing the connectedness of the vesselness map and inspecting the synthesized tensor field as proof of concept. VTrails performance is evaluated on images with different levels of degradation: we verify that the extracted vascular network is an acyclic graph (i.e. a tree), and we report the extraction accuracy, precision and recall

The renal resistive index is associated with microvascular remodeling in patients with severe obesity

BACKGROUND Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. METHODS We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with N G -nitro arginine methyl ester (L-NAME), were measured. RESULTS Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT ( P = 0.042). Multivariable analysis showed a relationship between M/L and RRI ( P  = 0.016, St. β 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation ( P   =  0.036, St. β = -0.34). Notably, all these correlations were consistent also after adjustment for confounding factors. CONCLUSIONS The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption

Evaluation of Three Different Vaccination Protocols against EHV1/EHV4 Infection in Mares: Double Blind, Randomized Clinical Trial

Abstract: EHV1 and EHV4 are the most important herpesviruses in horses. Repeated cases of abortion in mares regularly vaccinated, prompted us to investigate the immune response after vaccination with the same inactivated vaccine, but with three dierent protocols. Eighteen mares were chosen and randomly divided in three study groups (G1-G2-G3) and a control group (Ctrl). For serologic and PCR investigations nasal swabs, sera and blood were collected. The protocol used in G3 (4 doses) increased the titer recorded by ELISA and seroneutralization (SN). Poor agreement and no correlation were observed in titer values between ELISA and SN and between SN and PCR. A very weak positive correlation between ELISA and PCR was obtained. Seven out of 18 nasal swabs were positive by PCR; none showed viremia and no abortion occurred, regardless of vaccination status and despite active circulation of EHV-1 in the farm at the time of the study. The study was conducted in field conditions, in a susceptible population with a known history of infection and abortion, and among the three protocols, the one proposed in the G1 was the least ecient while the one proposed for the G3, seems to have induced a higher antibody titer in both SN and ELISA

Framework to generate perfusion map from CT and CTA images in patients with acute ischemic stroke: A longitudinal and cross-sectional study

Stroke is a leading cause of disability and death. Effective treatment decisions require early and informative vascular imaging. 4D perfusion imaging is ideal but rarely available within the first hour after stroke, whereas plain CT and CTA usually are. Hence, we propose a framework to extract a predicted perfusion map (PPM) derived from CT and CTA images. In all eighteen patients, we found significantly high spatial similarity (with average Spearman's correlation = 0.7893) between our predicted perfusion map (PPM) and the T-max map derived from 4D-CTP. Voxelwise correlations between the PPM and National Institutes of Health Stroke Scale (NIHSS) subscores for L/R hand motor, gaze, and language on a large cohort of 2,110 subjects reliably mapped symptoms to expected infarct locations. Therefore our PPM could serve as an alternative for 4D perfusion imaging, if the latter is unavailable, to investigate blood perfusion in the first hours after hospital admission.Comment: Accepted and presented in SWITCH2023: Stroke Workshop on Imaging and Treatment CHallenges (MICCAI 2023, Vancouver Canada

Robustness of the wide-field imaging Mueller polarimetry for brain tissue differentiation and white matter fiber tract identification in a surgery-like environment: an ex vivo study.

During neurooncological surgery, the visual differentiation of healthy and diseased tissue is often challenging. Wide-field imaging Muller polarimetry (IMP) is a promising technique for tissue discrimination and in-plane brain fiber tracking in an interventional setup. However, the intraoperative implementation of IMP requires realizing imaging in the presence of remanent blood, and complex surface topography resulting from the use of an ultrasonic cavitation device. We report on the impact of both factors on the quality of polarimetric images of the surgical resection cavities reproduced in fresh animal cadaveric brains. The robustness of IMP is observed under adverse experimental conditions, suggesting a feasible translation of IMP for in vivo neurosurgical applications