Determining clinically-viable biomarkers for ischaemic stroke through a mechanistic and machine learning approach

Assessment of distal cerebral perfusion after ischaemic stroke is currently only possible through expensive and time-consuming imaging procedures which require the injection of a contrast medium. Alternative approaches that could indicate earlier the impact of blood flow occlusion on distal cerebral perfusion are currently lacking. The aim of this study was to identify novel biomarkers suitable for clinical implementation using less invasive diagnostic techniques such as Transcranial Doppler (TCD). We used 1D modelling to simulate pre- and post-stroke velocity and flow wave propagation in a typical arterial network, and Sobol’s sensitivity analysis, supported by the use of Gaussian process emulators, to identify biomarkers linked to cerebral perfusion. We showed that values of pulsatility index of the right anterior cerebral artery > 1.6 are associated with poor perfusion and may require immediate intervention. Three additional biomarkers with similar behaviour, all related to pulsatility indices, were identified. These results suggest that flow pulsatility measured at specific locations could be used to effectively estimate distal cerebral perfusion rates, and ultimately improve clinical diagnosis and management of ischaemic stroke

A multiscale computational framework to evaluate flow alterations during mechanical thrombectomy for treatment of ischaemic stroke

The treatment of ischaemic stroke increasingly relies upon endovascular procedures known as mechanical thrombectomy (MT), which consists in capturing and removing the clot with a catheter-guided stent while at the same time applying external aspiration with the aim of reducing haemodynamic loads during retrieval. However, uniform consensus on procedural parameters such as the use of balloon guide catheters (BGC) to provide proximal flow control, or the position of the aspiration catheter is still lacking. Ultimately the decision is left to the clinician performing the operation, and it is difficult to predict how these treatment options might influence clinical outcome. In this study we present a multiscale computational framework to simulate MT procedures. The developed framework can provide quantitative assessment of clinically relevant quantities such as flow in the retrieval path and can be used to find the optimal procedural parameters that are most likely to result in a favorable clinical outcome. The results show the advantage of using BGC during MT and indicate small differences between positioning the aspiration catheter in proximal or distal locations. The framework has significant potential for future expansions and applications to other surgical treatments

Improved biomechanical metrics of cerebral vasospasm identified via sensitivity analysis of a 1D cerebral circulation model

Cerebral vasospasm (CVS) is a life-threatening condition that occurs in a large proportion of those affected by subarachnoid haemorrhage and stroke. CVS manifests itself as the progressive narrowing of intracranial arteries. It is usually diagnosed using Doppler ultrasound, which quantifies blood velocity changes in the affected vessels, but has low sensitivity when CVS affects the peripheral vasculature. The aim of this study was to identify alternative biomarkers that could be used to diagnose CVS. We used a 1D modelling approach to describe the properties of pulse waves that propagate through the cardiovascular system, which allowed the effects of different types of vasospasm on waveforms to be characterised at several locations within a simulated cerebral network. A sensitivity analysis empowered by the use of a Gaussian process statistical emulator was used to identify waveform features that may have strong correlations with vasospasm. We showed that the minimum rate of velocity change can be much more effective than blood velocity for stratifying typical manifestations of vasospasm and its progression. The results and methodology of this study have the potential not only to improve the diagnosis and monitoring of vasospasm, but also to be used in the diagnosis of many other cardiovascular diseases where cardiovascular waves can be decoded to provide disease characterisation

Role of distal cerebral vasculature in vessel constriction after aneurysm treatment with flow diverter stents

Background Treatment of intracranial aneurysms with flow diverter stent (FDS) procedures can lead to caliber changes of jailed vessels. The reason some branches remain unchanged and others are affected by narrowing remains unknown. Objective To investigate the influence of resistance to flow from distal vasculature on stent-induced hemodynamic modifications affecting bifurcating vessels. Materials and methods Radiological images and demographic data were acquired for 142 aneurysms treated with a FDS. Vascular resistance was estimated from patient-specific anatomic data. Correlation analysis was used to identify correspondence between anatomic data and clinical outcome. Computational Fluid Dynamics was performed on a typical patient-specific model to evaluate the influence of FDS on flow. Relevant hemodynamic variables along the bifurcating vessels were quantitatively analyzed and validated with in vitro data obtained using power Doppler ultrasound. Results Statistical analysis showed a correlation between clinical outcome and FDS resistance to flow considering overall jailed vessel vascular resistance (r=0.5, P<0.001). Computational predictions of blood flow showed that hemodynamics is minimally affected by FDS treatment in the ophthalmic artery. Conclusions Jailed vessels are affected by narrowing when resistance to flow from the FDS constitutes a larger proportion of the overall vessel resistance to flow. This knowledge may contribute to better understanding of intracranial hemodynamics after a FDS procedure and reinforce indications for flow diversion in the treatment of intracranial aneurysms

A clinically aligned experimental approach for quantitative characterization of patient-specific cardiovascular models

Recent improvements in computational tools opened the possibility of patient-specific modeling to aid clinicians during diagnosis, treatment, and monitoring. One example is the modeling of blood flow for surgical planning, where modeling can help predict the prognosis. Computational analysis is used to extract hemodynamic information about the case; however, these methods are sensitive to assumptions on blood properties, boundary conditions, and appropriate geometry accuracy. When available, experimental measurements can be used to validate the results and, among the modalities, ultrasound-based methods are suitable due to their relative low cost and non-invasiveness. This work proposes a procedure to create accurate patient-specific silicone replicas of blood vessels and a power Doppler compatible experimental setup able to simulate and measure realistic flow conditions. The assessment of silicone model geometry shows small discrepancies between these and the target geometries (median of surface error lies within 57 µm and 82 μm). Power Doppler measurements were compared against computational fluid dynamics results, showing discrepancies within 10% near the wall. The experimental approach offers a setup to quantify flow in in vitro systems and provide more accurate results where other techniques (e.g., particle image velocimetry and particle tracking velocimetry) have shown limitations due to the interference of the interface

Reversible brain edema associated to flow diverter stent procedures: a retrospective single-center study to evaluate frequency, clinical evolution, and possible mechanism

Background Hemorrhage and ischemia after flow diverter stent (FDS) procedures for intracranial aneurysms are the most common complications and have been extensively described. Temporary brain edema (TBE) is an unknown complication that could be associated with particular FDS procedures. Objective To estimate the frequency, clinical presentation, imaging findings, and possible mechanisms associating TBE with FDS. Methods Unruptured aneurysms treated with FDS implantation performed in our service from June 2015 to March 2018 were reviewed. Medical antecedents, endovascular procedure, clinical assessments before and after treatment, aneurysm characteristics, and image records were collected. Artery diameters of patients in whom TEB developed were also calculated to investigate any correlation between TBE and anatomic descriptors. Results A total of 179 FDS procedures in 176 patients were reviewed. Six patients (3.4%) presented with symptomatic TBE, and all TBE patients had undergone FDS implantation from the middle cerebral artery (MCA) to the internal carotid artery (ICA). A Pearson product-moment correlation coefficient (PPCC) found smaller MCA diameters and MCA/ICA ratios in these 6 patients (respectively PPCC = −0.619, P < 0.04; PPCC = −0.647, P < 0.03). Hemorrhagic and ischemic complications were less frequent than TBE (2.3% and 1.1% vs. 3.4%). Conclusions TBE was more frequent than ischemic or hemorrhagic complications after FDS in this study. TBE seemed to be associated with a particular FDS positioning in small arteries, inducing flow changes and disruption of the blood–brain barrier

Strokes in the anterior circulation: comparison between bridging and intravenous thrombolysis.

BACKGROUND AND PURPOSE: To compare safety and efficacy of bridging approach with intravenous (IV) thrombolysis in patients with acute anterior strokes and proximal occlusions. PATIENTS AND METHODS: Consecutive patients with ischemic anterior strokes admitted within a 4 h 30 min window in two different centers were included. The first center performed IV therapy (alteplase 0.6 mg/kg) during 30 min and, in absence of clinical improvement, mechanical thrombectomy with flow restoration using a Solitaire stent (StS); the second carried out IV thrombolysis (alteplase 0.9 mg/kg) alone. Only T, M1 or M2 occlusions present on CT angiography were considered. Endpoints were clinical outcome and mortality at 3 months. RESULTS: There were 63 patients in the bridging and 163 in the IV group. No significant differences regarding baseline characteristics were observed. At 3 months, 46% (n = 29) of the patients treated in the combined and 23% (n = 38) of those treated in the IV group had a modified Rankin scale (mRS) of 0-1 (P &lt; 0.001). A statistical significant difference was observed for all sites of occlusion. In a logistic regression model, National Institute of Health Stroke Scale (NIHSS) and bridging therapy were independent predictors of good outcome (respectively, P = 0.001 and P = 0.0018). Symptomatic hemorrhage was documented in 6.3% vs 3.7% in the bridging and in the IV group, respectively (P = 0.32). There was no difference in mortality. CONCLUSIONS: Our results suggest that patients treated with a bridging approach were more likely to have minimal or no deficit at all at 3 months as compared to the IV treated group

The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm Treatment with Flow-Diverter Stents

BACKGROUND AND PURPOSE: Treatment of intracranial bifurcation aneurysms with flow-diverter stents can lead to caliber changes of the distal vessels in a subacute phase. This study aims to evaluate whether local anatomy and flow disruption induced by flow-diverter stents are associated with vessel caliber changes in intracranial bifurcations. MATERIALS AND METHODS: Radiologic images and demographic data were acquired for 25 patients with bifurcation aneurysms treated with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were used to evaluate if anatomic data and caliber changes could be linked. Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized and patient-specific anatomies to evaluate flow changes induced by flow-diverter stents in the jailed vessel. RESULTS: Statistical analysis identified a marked correspondence between asymmetric bifurcation and caliber change. Symmetry ratios were lower for cases showing narrowing or subacute occlusion (medium daughter vessel diameter ratio = 0.59) compared with cases with posttreatment caliber conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid dynamics analysis in idealized and patient-specific anatomies showed that wall shear stress in the jailed vessel was more affected when flow-diverter stents were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected when deployed in symmetric anatomies (diameter ratio ∼1.00). CONCLUSIONS: Anatomic data analysis showed statistically significant correspondence between caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P < .001). Similarly, computational fluid dynamics results showed the highest impact on hemodynamics when flow-diverter stents are deployed in asymmetric bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress fields. Further research and clinical validation are necessary to identify all elements involved in vessel caliber changes after flow-diverter stent procedures