Simulation of a mechanical thrombectomy device based in the use of self-expandable stents for the blood clots extraction

Recently, we have presented some studies concerning the analysis, design and optimization of one experimental device developed in the UK - GPTAD - which has been designed to remove blood clots without the need to make contact with the clot itself, thereby potentially reducing the risk of problems such as downstream embolisation. Based on the idea of a modification of the previous device, in this work, we present a model based in the use of stents like the SolitaireTM FR, which is in contact with the clot itself. In the case of such devices, the stent is self-expandable and the extraction of the blood clot is faciliatated by the stent, which must be inside the clot. Such stents are generally inserted in position by using the guidewire inserted into the catheter. This type of modeling could potentially be useful in showing how the blood clot is moved by the various different forces involved. The modelling has been undertaken by analyzing the resistances, compliances and inertances effects. We model an artery and blood clot for range of forces for the guidewire. In each case we determine the interaction between blood clot, stent and artery

Computational Fluid Dynamics (CFD) Simulation for the Extraction of Blood Clot in Middle Cerebral Artery using ‘GP’ 2 Device

Stroke has become the number three killer disease in Malaysia following heart disease and cancer; with 110 of people dying from it every day. The effects of stroke often lead to life-changing, permanent impairment to the patients such as paralysis, speech and logic sequencing. Hence, recent studies are looking into stroke treatments with minimal after surgical effect to patients. One of the alternatives is using mechanical thrombectomy devices. In this project, the simulation for ‘GP’ 2 device which functions to extract the blood clot in the artery without damaging the arterial wall and causing downstream embolism is presented. The simulation will be carried out using computational fluid dynamics; applying the Volume of Fluid (VOF) model. In grid size selection, it is clear that finer grids results in higher accuracy calculations i.e. better results. However, this is achieved at the cost of prolonged computational time. From grid sensitivity study in identifying the optimum grid size that is fine enough to generate accurate calculations but large enough to avoid extra computational time; the grid size of 0.2mm is used. The design for ‘GP’ 2 Device has to be characterised to identify which of the two proposed designs is efficient for the suction of blood clot for 100% occlusion in the Middle Cerebral Artery. Design for ‘GP’ 2 Model 1 device is better at clot extraction than the Model 2 device because increase in surface area for suction favours same-suction principle rather than vortex creation to break the clot. Theoretically, higher pressure results in faster clot extraction. However, the value of pressure applied shall be observed closely so that no arterial damage is done and it can be applied for clinical tests. For both models, it can be shown that higher pressure extracts blood clot at lower time whereby the fastest clot extraction occurs at time 0.00498s for Model 1, and 0.01211s for Model 2 both at 60 kPa

Performance of a thrombectomy device for aspiration of thrombus with various sizes based on a computational fluid dynamic modelling

It is important to thoroughly remove the thrombus within the course of aspiration thrombectomy; otherwise, it may lead to further embolization. The performance of the aspiration thrombectomy device with a generic geometry is studied through the computational approach. In order to model the thrombus aspiration, a real left coronary artery is chosen while thrombi with various sizes are located at the bifurcation area of the coronary artery and, depending on the size of the thrombus, it is stretched toward the side branches. The thrombus occupies the artery resembling the blood current obstruction in the coronary vessel similar to the situation that leads to heart attack. It is concluded that the aspiration ability of the thrombectomy device is not linked to the thrombus size; it is rather linked to the aspiration pressure and thrombus age (organized versus fresh thrombus). However, the aspiration time period correlates to the thrombus size. The minimum applicable aspiration pressure is also investigated in this study

Computational Fluid Dynamics (CFD) Simulation for the Extraction of Blood Clot in Middle Cerebral Artery using ‘GP’ 2 Device

Stroke has become the number three killer disease in Malaysia following heart disease and cancer; with 110 of people dying from it every day. The effects of stroke often lead to life-changing, permanent impairment to the patients such as paralysis, speech and logic sequencing. Hence, recent studies are looking into stroke treatments with minimal after surgical effect to patients. One of the alternatives is using mechanical thrombectomy devices. In this project, the simulation for ‘GP’ 2 device which functions to extract the blood clot in the artery without damaging the arterial wall and causing downstream embolism is presented. The simulation will be carried out using computational fluid dynamics; applying the Volume of Fluid (VOF) model. In grid size selection, it is clear that finer grids results in higher accuracy calculations i.e. better results. However, this is achieved at the cost of prolonged computational time. From grid sensitivity study in identifying the optimum grid size that is fine enough to generate accurate calculations but large enough to avoid extra computational time; the grid size of 0.2mm is used. The design for ‘GP’ 2 Device has to be characterised to identify which of the two proposed designs is efficient for the suction of blood clot for 100% occlusion in the Middle Cerebral Artery. Design for ‘GP’ 2 Model 1 device is better at clot extraction than the Model 2 device because increase in surface area for suction favours same-suction principle rather than vortex creation to break the clot. Theoretically, higher pressure results in faster clot extraction. However, the value of pressure applied shall be observed closely so that no arterial damage is done and it can be applied for clinical tests. For both models, it can be shown that higher pressure extracts blood clot at lower time whereby the fastest clot extraction occurs at time 0.00498s for Model 1, and 0.01211s for Model 2 both at 60 kPa

Towards clinical assessment of cerebral blood flow regulation using ultrasonography : model applicability in clinical studies

For preservation of its vital functions, the brain is largely dependent of a sufficient delivery of oxygen and nutrients. Blood flow to the brain is essentially regulated by 2 control mechanisms i.e. neurovascular coupling and cerebral autoregulation. Cerebral autoregulation aims for constant adequate blood supply by compensating for blood pressure variations by dilatation or narrowing of the cerebral microvasculature. Neurovascular coupling adjusts blood supply to the local metabolic need. Cerebral perfusion and blood flow regulation are compromised in several pathological conditions. Clinical examination of cerebral blood flow and its regulation may therefore provide helpful diagnostic, predictive and therapeutic information. The work in this thesis was aimed at putting a step forward towards development of reliable and clinically usable parameters for cerebral blood flow regulation assessment using ultrasonography. Regarding early diagnostics, screening and monitoring of cerebral blood flow and its regulation, ultrasonography has major advantages over other imaging tools because of its noninvasiveness, cost-effectiveness, easy usability and its good time resolution. It allows examination of blood flow velocities at multiple locations throughout the extra- and intracranial circulation and evaluation of both control mechanisms by transfer function analysis. For evaluation of cerebral autoregulation, transcranial Doppler blood flow velocities in the large middle cerebral arteries have been recorded simultaneously with plethysmographic (finger) blood pressure. Gain and phase of the pressure-flow transfer function have been determined to obtain quantitative measures for cerebral autoregulation. Neurovascular coupling has been assessed by presenting a visual block stimulus to a subject and simultaneous measurement of the blood flow velocity in the artery exclusively supplying the visual cortex. The obtained visually-evoked blood flow response (VEFR) has been considered as the step response of a linear second order control system model providing patient-specific parameters such as gain and damping as quantitative measures for neurovascular coupling . In chapter 2, a clinical study has been described in which extra- and intracranial blood flow velocities (BFVs), measured at multiple sites in the circulation, have been compared between Alzheimer patients (AD), patients with mild cognitive impairment (MCI) and healthy aging controls (HC). BFVs of AD were significantly lowered at proximal sites but preserved at distal sites for the internal carotid artery and middle and posterior cerebral arteries as compared to those of MCI or HC. This specific pattern can presumably be ascribed to reduced distal diameters resulting from AD pathology. MCI BFV were similar to HC BFV in the extracranial and intracranial posterior circulation, whereas they were intermediate between AD and HC in the intracranial anterior circulation. This suggests that intracranial anterior vessels are most suitable for early detection of pathological alterations resulting from AD. The study findings further indicate that extensive ultrasonographic screening of intra- and extracranial arteries is useful for monitoring BFV decline in the MCI stage. Future follow-up of MCI patients may reveal the predictive value of location-specific BFV for conversion to AD. In the same study cohort, dynamic cerebral autoregulation has been studied as discussed in chapter 3. Cerebral autoregulatory gain and phase values were similar for AD, MCI and HC which implies that the cerebral autoregulatory mechanism is preserved in AD. However, the cerebrovascular resistance index i.e. the ratio between absolute time-averaged blood pressure and flow velocity, was significantly higher in AD as compared to MCI and HC indicating that vessel stiffness is increased in AD. Indeed, it appeared to be a potential biomarker for AD development of MCI. The cerebrovascular resistance increase in AD was furthermore confirmed by windkessel model findings of a significantly elevated peripheral resistance in AD. Arterial resistance and peripheral compliance were equal for all groups. From chapter 4, the focus was shifted to assessment of local blood flow regulation. Visuallyevoked blood flow responses (VEFRs) of formerly (pre-)eclamptic patients and healthy controls have been examined to evaluate neurovascular coupling first in a relative young study population. The aim of the study was to investigate whether possible local (pre)eclampsia-induced endothelial damage was reversible or not. The measured VEFRs have been fitted with the step response of a 2nd order control system model. Although inter-group differences in model parameters were not found, a trend was observed that critical damping (z>1) occurred more frequently in former patients than in controls. Critical damping reflects an atypical VEFR, which is either uncompensated (sluggish, z>1; Tv <20) or compensated by a rise in rate time (intermediate, z>1; Tv > 20). Since these abnormal VEFRs were mainly found in former patients (but not exclusively), these response types were hypothesized to result from pathological disturbances. A revised VEFR analysis procedure to account for reliability and blood pressure dynamics has been proposed in chapter 5. This revised procedure consists of the introduction of a reliability measure for model parameters and of a model extension to consider possible blood pressure contribution to the measured VEFR. The effects of these adjustments on study outcomes have been evaluated by applying both the standard VEFR analysis procedure (applied in chapter 4) and the revised procedure to the AD study cohort. Reliability consideration resulted in about 40% VEFR exclusion, mainly due to the models’ inability to fit critically damped responses. Reliability consideration reduced parameter variability substantially. Regarding the influence of blood pressure variation, a significantly increased damping was found in AD for the standard but not for the revised model. This reversed the study conclusion from altered to normal neurovascular coupling in AD. Considering their influence on obtained parameters, both aspects i.e. reliability and blood pressure variation should be included in VEFR-analysis. Regarding clinical study outcomes, neurovascular coupling seems to be unaffected in AD since the finding of an increased damping may be ascribed to ignorance of blood pressure contribution to VEFR. Study conclusions of earlier chapters (4 and 5) emphasize the need for a model incorporating physiological features. In chapter 6, preliminary results have been reported of the application of a newly developed lumped parameter model of the visual cortex vasculature to the 3 different VEFR types. In the new model, regulatory processes i.e. neurogenic, metabolic, myogenic and shear stress mechanisms, act on smooth muscle tone which inherently leads to adjustment of microcirculatory resistance and compliance. This allows the study of effects of pathological changes on the VEFR. It may be concluded that the model provides an improved link between VEFR and physiology. Preliminary results show that the physiology-based model can describe VEFR type representatives reasonably well obtaining physiologically plausible parameter values. Thus, from a clinical perspective it may be concluded that (Duplex) ultrasonography has great potential as a standard screening tool for MCI patients. It seems worthwhile to examine all future MCI patients on extra- and intracranial blood flow velocity and to determine their cerebrovascular resistance index by simultaneous blood pressure recording. Follow-up of MCI patients will reveal the predictive value of these parameters for future AD development. Furthermore, from a methodological perspective, it can be concluded that the current standard of control system analysis to assess local cerebral blood flow regulation has limitations regarding parameter reliability and VEFR interpretation. Both reliability and interpretation may be improved by optimization and control of data acquisition quality and by use of physiology-based models. Physiological mechanisms influencing VEFR establishment should be incorporated in such a model to possibly explain part of its variance. Efforts should be directed to development and validation of physiology-based models aimed at reliable description of VEFRs by physiologically meaningful parameters

The detection of intracranial aneurysms by non-invasive imaging methods and the epidemiology of aneurysmal subarachnoid haemorrhage within the Scottish population

The aims of the research project, which led to the writing of this thesis were to: Examine whether non -invasive imaging methods could replace intra- arterial angiography (IADSA) in the detection of intracranial aneurysms by: a) systematically reviewing the literature; b) prospectively determining the accuracy of the non -invasive imaging methods currently available in Scotland, including the effect of observer experience on diagnostic performance and the patient acceptability of the alternative imaging modalities. To establish the incidence of aneurysmal subarachnoid haemorrhage (SAH) in families by a national retrospective study of occurrences of SAH in a one year period in Scotland, in parallel with a follow -up study of the families of patients who were admitted to the Institute of Neurosciences with aneurysmal SAH a decade earlier. The thesis is divided into three parts:PART ONE: a) summarises the current understanding of the epidemiology and pathophysiology of intracranial aneurysms; b) an overview of cerebrovascular anatomy with reference to aneurysm formation; c) the modalities available for imaging intracranial aneurysms and the current knowledge about their diagnostic performance are considered; d) an overview of the methods available for the treatment of intracranial aneurysms; e) the concept of screening for unruptured intracranial aneurysms is discussed and placed in context by comparison to other screening programmes.PART TWO: a) describes a systematic review of the non -invasive imaging of intracranial aneurysms. CT and MR angiography had similar accuracy compared to IADSA of ~90 %. Data on Transcranial Doppler Sonography (TCDS) were scanty but indicated poorer performance. Detection of very small aneurysms (<3mm diameter) was significantly poorer for the non -invasive tests; b) describes a prospective study of 200 patients examining CTA, MRA and TCDS vs IADSA in the detection of intracranial aneurysms. CTA and MRA had an accuracy (per subject) of 0.85. TCDS had similar accuracy per subject but poorer accuracy per aneurysm than CTA or MRA. Detection of aneurysms ≤5mm was significantly poorer than for those >5mm. Interobserver agreement was good for all modalities; c) combining TCDS with CTA or MRA improved the detection of aneurysms on a per subject basis. Non-invasive imaging tests, especially when used in combination, are reliable at detecting aneurysms >5mm; d) examines the effect of observer experience. Neuroradiologists were more consistent and had better agreement with IADSA than non - neuroradiologists. Small aneurysms and cavernous /terminal internal carotid aneurysms were poorly detected by all observers; e) assessment of patient preferences indicated that TCDS was preferred to the other non -invasive tests and CTA to MRA, with the differences being statistically significant.PART THREE describes: a) the rationale behind the epidemiological studies; b) the methodology used; c) describes the results: Comparative risk for 1st vs 2nd degree relatives suffering a SAH was 2.29 for the Scotland wide study (SWS) and 2.43 for the West of Scotland study (WOS). Absolute lifetime SAH risk was 4.7% for 1st degree and 1.9% for 2nd degree relatives in the SWS compared to 4.2% and 2.3% respectively in the WOS. Prospective 10 -year SAH risk was 1.2% for a 1st degree and 0.5% for a 2nd degree relative compared to background population risk of ~0.1%. The hierarchy of risk was greatest for a member of a family with ≥ 2 other 1st degree relatives affected by SAH, with a more than 20-fold increased risk over the background population risk; d) discusses the implications of the findings and examines the strengths and weaknesses of the study. Routine screening of families of patients who have had a SAH is not supported by these data; e) reviews the implications for i) clinical practice and ii) future research arising from the imaging and epidemiological studies