Spatiotemporal Hemodynamic Complexity in Carotid Arteries: An Integrated Computational Hemodynamics and Complex Networks-Based Approach

Objective: The study of the arterial hemodynamics is essential for a better understanding of the risks associated with the onset/progression of vascular disease. However, conventional quantification and visualization paradigms are not sufficient to fully capture the spatiotemporal evolution of correlated blood flow patterns and their “sphere of influence” in complex vascular geometries. In the attempt to bridge this knowledge gap, an integrated computational hemodynamics and complex networks-based approach is proposed to unveil organization principles of cardiovascular flows. Methods: The approach is applied to ten patient-specific hemodynamic models of carotid bifurcation, a vascular bed characterized by a complex hemodynamics and clinically-relevant disease. Correlation-based networks are built starting from time-histories of two fluid mechanics quantities of physiological significance, respectively (1) the blood velocity vector axial component locally aligned with the main flow direction, and (2) the kinetic helicity density. Results: Unlike conventional hemodynamic analyses, here the spatiotemporal similarity of dynamic intravascular flow structures is encoded in a distance function. In the case of the carotid bifurcation, this study measures for the first time to what extent flow similarity is disrupted by vascular geometric features. Conclusion: It emerges that a larger bifurcation expansion, a hallmark of vascular disease, significantly disrupts the network topological connections between axial flow structures, reducing also their anatomical persistence length. On the contrary, connections in helical flow patterns are overall less geometry-sensitive. Significance: The integrated approach proposed here, by exploiting the connections of hemodynamic patterns undergoing similar dynamical evolution, opens avenues for further comprehension of vascular physiopathology

Wall shear stress topological skeleton independently predicts long-term restenosis after carotid bifurcation endarterectomy

Wall Shear Stress (WSS) topological skeleton, composed by fixed points and the manifolds linking them, reflects the presence of blood flow features associated to adverse vascular response. However, the influence of WSS topological skeleton on vascular pathophysiology is still underexplored. This study aimed to identify direct associations between the WSS topological skeleton and markers of vascular disease from real-world clinical longitudinal data of long-term restenosis after carotid endarterectomy (CEA). Personalized computational hemodynamic simulations were performed on a cohort of 13 carotid models pre-CEA and at 1 month after CEA. At 60 months after CEA, intima-media thickness (IMT) was measured to detect long-term restenosis. The analysis of the WSS topological skeleton was carried out by applying a Eulerian method based on the WSS vector field divergence. To provide objective thresholds for WSS topological skeleton quantitative analysis, a computational hemodynamic dataset of 46 ostensibly healthy carotid bifurcation models was considered. CEA interventions did not completely restore physiological WSS topological skeleton features. Significant associations emerged between IMT at 60 months follow-up and the exposure to (1) high temporal variation of WSS contraction/expansion (R2 = 0.51, p < 0.05), and (2) high fixed point residence times, weighted by WSS contraction/expansion strength (R2 = 0.53, p < 0.05). These WSS topological skeleton features were statistically independent from the exposure to low WSS, a previously reported predictor of long-term restenosis, therefore representing different hemodynamic stimuli and potentially impacting differently the vascular response. This study confirms the direct association between WSS topological skeleton and markers of vascular disease, contributing to elucidate the mechanistic link between flow disturbances and clinical observations of vascular lesions

WALL SHEAR STRESS TOPOLOGICAL SKELETON IDENTIFICATION IN CARDIOVASCULAR FLOWS: A PRACTICAL APPROACH

The observed co-localization of “disturbed” hemodynamics and atherosclerotic lesion prevalence has led to the identification of low and oscillatory Wall Shear Stress (WSS) as a biomechanical localizing factor for vascular dysfunction. However, recent evidences have underlined how consideration of only “low and oscillatory” WSS may oversimplify the complex hemodynamic milieu to which the endothelium is exposed. In this context, recent studies have highlighted the relevance of WSS fixed points, and the stable and unstable manifolds that connect them. These WSS topological features have a strong link with flow features like flow stagnation, separation, and recirculation, which are usually classified as “disturbed” flow. Technically, a fixed point of a vector field is a point where the vector field vanishes, while unstable/stable vector field manifolds identify contraction/expansion regions linking the fixed points. The set of fixed points and their connections form the topological skeleton of a vector field. The presence of WSS fixed points and of WSS contraction/expansion regions, highlighted by WSS manifolds, might induce focal vascular responses relevant for, e.g., early atherosclerosis, or, aneurysm rupture. For these reasons, the topological skeleton analysis of the WSS vector field is of great interest and motivates the study present herein. Lagrangian techniques have been recently proposed to identify WSS manifolds but have certain practical limitations. A Eulerian approach has also been suggested, but only for 2D analytical fields. Here we propose and demonstrate the use of a simple Eulerian approach for identifying WSS topological skeleton on 3D surfaces

Computational hemodynamics & complex networks integrated platform to study intravascular flow in the carotid bifurcation

The well-established role of hemodynamics in cardiovascular disease [1] makes the study of cardiovascular flows of wide interest. Here we apply for the first time a method based on complex networks (CNs) theory [2] to investigate and characterize quantitatively the complexity of cardiovascular flows. The rationale lies in the ability of CNs to explore the complexity of physical systems, such as 4D cardiovascular flows, in a synthetic and effective manner. CN-based approaches have already proven useful for data-driven learning of dynamical processes that are hidden to other analysis techniques. In detail, a dataset of 10 patient-specific computational hemodynamics models of human carotid bifurcation (CB) is considered here. Quantitative metrics derived from CNs theory are applied to two fluid mechanics quantities describing the intricate intravascular hemodynamics. These are (1) the so-called axial velocity, i.e. the blood velocity component aligned with the main flow direction, as identified by the vessels centerline, and (2) the kinetic helicity density, a measure of pitch and torsion of the streaming blood. The obtained results suggest the potency of CNs in unveiling fundamental organization principles in cardiovascular flows

Wall shear stress topological skeleton analysis in cardiovascular flows: Methods and applications

A marked interest has recently emerged regarding the analysis of the wall shear stress (WSS) vector field topological skeleton in cardiovascular flows. Based on dynamical system theory, the WSS topological skeleton is composed of fixed points, i.e., focal points where WSS locally vanishes, and unstable/stable manifolds, consisting of contraction/expansion regions linking fixed points. Such an interest arises from its ability to reflect the presence of near-wall hemodynamic features associated with the onset and progression of vascular diseases. Over the years, Lagrangian-based and Eulerianbased post-processing techniques have been proposed aiming at identifying the topological skeleton features of the WSS. Here, the theoretical and methodological bases supporting the Lagrangian- and Eulerian-based methods currently used in the literature are reported and discussed, highlighting their application to cardiovascular flows. The final aim is to promote the use of WSS topological skeleton analysis in hemodynamic applications and to encourage its application in future mechanobiology studies in order to increase the chance of elucidating the mechanistic links between blood flow disturbances, vascular disease, and clinical observations

Smartphone-based particle image velocimetry for cardiovascular flows applications: A focus on coronary arteries

An experimental set-up is presented for the in vitro characterization of the fluid dynamics in personalized phantoms of healthy and stenosed coronary arteries. The proposed set-up was fine-tuned with the aim of obtaining a compact, flexible, low-cost test-bench for biomedical applications. Technically, velocity vector fields were measured adopting a so-called smart-PIV approach, consisting of a smartphone camera and a low-power continuous laser (30 mW). Experiments were conducted in realistic healthy and stenosed 3D-printed phantoms of left anterior descending coronary artery reconstructed from angiographic images. Time resolved image acquisition was made possible by the combination of the image acquisition frame rate of last generation commercial smartphones and the flow regimes characterizing coronary hemodynamics (velocities in the order of 10 cm/s). Different flow regimes (Reynolds numbers ranging from 20 to 200) were analyzed. The smart-PIV approach was able to provide both qualitative flow visualizations and quantitative results. A comparison between smart-PIV and conventional PIV (i.e., the gold-standard experimental technique for bioflows characterization) measurements showed a good agreement in the measured velocity vector fields for both the healthy and the stenosed coronary phantoms. Displacement errors and uncertainties, estimated by applying the particle disparity method, confirmed the soundness of the proposed smart-PIV approach, as their values fell within the same range for both smart and conventional PIV measured data (≈5% for the normalized estimated displacement error and below 1.2 pixels for displacement uncertainty). In conclusion, smart-PIV represents an easy-to-implement, low-cost methodology for obtaining an adequately robust experimental characterization of cardiovascular flows. The proposed approach, to be intended as a proof of concept, candidates to become an easy-to-handle test bench suitable for use also outside of research labs, e.g., for educational or industrial purposes, or as first-line investigation to direct and guide subsequent conventional PIV measurements

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS &lt; 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders