Mathematical modelling of haemorrhagic transformation within a multiscale microvasculature network

Abstract Objective. Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke, caused by damage to the blood–brain barrier (BBB) that could be the result of stroke progression or a complication of stroke treatment with reperfusion therapy. The aim of this study is to develop further a previous simple HT mathematical model into an enlarged multiscale microvasculature model in order to investigate the effects of HT on the surrounding tissue and vasculature. In addition, this study investigates the relationship between tissue displacement and vascular geometry. Approach. By modelling tissue displacement, capillary compression, hydraulic conductivity in tissue and vascular permeability, we establish a mathematical model to describe the change of intracranial pressure (ICP) surrounding the damaged vascular bed after HT onset, applied to a 3D multiscale microvasculature. The use of a voxel-scale model then enables us to compare our HT simulation with available clinical imaging data for perfusion and cerebral blood volume ( C B V ) in the multiscale microvasculature network. Main results. We showed that the haematoma diameter and the maximum tissue displacement are approximately proportional to the diameter of the breakdown vessel. Based on the voxel-scale model, we found that perfusion reduces by approximately 13 – 17 % and C B V reduces by around 20 – 25 % after HT onset due to the effect of capillary compression caused by increased interstitial pressure. The results are in good agreement with the limited experimental data. Significance. This model, by enabling us to bridge the gap between the microvascular scale and clinically measurable parameters, providing a foundation for more detailed validation and understanding of HT in patients.</jats:p

Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment:A Retrospective Cohort Study

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16-2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/; Unique identifier: ISRCTN10888758

Added Prognostic Value of Hemorrhagic Transformation Quantification in Patients With Acute Ischemic Stroke

Introduction and Aim: Hemorrhagic transformation (HT) frequently occurs after acute ischemic stroke and negatively influences the functional outcome. Usually, HT is classified by its radiological appearance. Discriminating between the subtypes can be complicated, and interobserver variation is considerable. Therefore, we aim to quantify rather than classify hemorrhage volumes and determine the association of hemorrhage volume with functional outcome in comparison with the European Cooperative Acute Stroke Study II classification. Patients and Methods: We included patients from the MR CLEAN trial with follow-up imaging. Hemorrhage volume was estimated by manual delineation of the lesion, and HT was classified according to the European Cooperative Acute Stroke Study II classification [petechial hemorrhagic infarction types 1 (HI1) and 2 (HI2) and parenchymal hematoma types 1 (PH1) and 2 (PH2)] on follow-up CT 24 h to 2 weeks after treatment. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with and without adjustment for potential confounders was used to describe the association of hemorrhage volume with functional outcome. We created regression models including and excluding total lesion volume as a confounder. Results: We included 478 patients. Of these patients, 222 had HT. Median hemorrhage volume was 3.37 ml (0.80–12.6) and per HT subgroup; HI1: 0.2 (0.0–1.7), HI2: 3.2 (1.7–6.1), PH1: 6.3 (4.2–13), and PH2: 47 (19–101). Hemorrhage volume was associated with functional outcome [adjusted common odds ratio (acOR): 0.83, 95% CI: 0.73–0.95] but not anymore after adjustment for total lesion volume (acOR: 0.99, 95% CI: 0.86–1.15, per 10 ml). Hemorrhage volume in patients with PH2 was significantly associated with functional outcome after adjusting total lesion volume (acOR: 0.70, 95% CI: 0.50–0.98). Conclusion: HT volume is associated with functional outcomes in patients with acute ischemic stroke but not independent of total lesion volume. The extent of a PH2 was associated with outcome, suggesting that measuring hemorrhage volume only provides an additional benefit in the prediction of the outcome when a PH2 is present

Mathematical modelling of haemorrhagic transformation within a multiscale microvasculature network

Objective.Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke, caused by damage to the blood-brain barrier (BBB) that could be the result of stroke progression or a complication of stroke treatment with reperfusion therapy. The aim of this study is to develop further a previous simple HT mathematical model into an enlarged multiscale microvasculature model in order to investigate the effects of HT on the surrounding tissue and vasculature. In addition, this study investigates the relationship between tissue displacement and vascular geometry.Approach.By modelling tissue displacement, capillary compression, hydraulic conductivity in tissue and vascular permeability, we establish a mathematical model to describe the change of intracranial pressure (ICP) surrounding the damaged vascular bed after HT onset, applied to a 3D multiscale microvasculature. The use of a voxel-scale model then enables us to compare our HT simulation with available clinical imaging data for perfusion and cerebral blood volume (CBV) in the multiscale microvasculature network.Main results. We showed that the haematoma diameter and the maximum tissue displacement are approximately proportional to the diameter of the breakdown vessel. Based on the voxel-scale model, we found that perfusion reduces by approximately13-17%andCBVreduces by around20-25%after HT onset due to the effect of capillary compression caused by increased interstitial pressure. The results are in good agreement with the limited experimental data.Significance. This model, by enabling us to bridge the gap between the microvascular scale and clinically measurable parameters, providing a foundation for more detailed validation and understanding of HT in patients

Mathematical modelling of haemorrhagic transformation within a multiscale microvasculature network

Objective.Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke, caused by damage to the blood-brain barrier (BBB) that could be the result of stroke progression or a complication of stroke treatment with reperfusion therapy. The aim of this study is to develop further a previous simple HT mathematical model into an enlarged multiscale microvasculature model in order to investigate the effects of HT on the surrounding tissue and vasculature. In addition, this study investigates the relationship between tissue displacement and vascular geometry.Approach.By modelling tissue displacement, capillary compression, hydraulic conductivity in tissue and vascular permeability, we establish a mathematical model to describe the change of intracranial pressure (ICP) surrounding the damaged vascular bed after HT onset, applied to a 3D multiscale microvasculature. The use of a voxel-scale model then enables us to compare our HT simulation with available clinical imaging data for perfusion and cerebral blood volume (CBV) in the multiscale microvasculature network.Main results. We showed that the haematoma diameter and the maximum tissue displacement are approximately proportional to the diameter of the breakdown vessel. Based on the voxel-scale model, we found that perfusion reduces by approximately13-17%andCBVreduces by around20-25%after HT onset due to the effect of capillary compression caused by increased interstitial pressure. The results are in good agreement with the limited experimental data.Significance. This model, by enabling us to bridge the gap between the microvascular scale and clinically measurable parameters, providing a foundation for more detailed validation and understanding of HT in patients

Thrombus imaging characteristics within acute ischemic stroke:similarities and interdependence

BACKGROUND: The effects of thrombus imaging characteristics on procedural and clinical outcomes after ischemic stroke are increasingly being studied. These thrombus characteristics - for eg, size, location, and density - are commonly analyzed as separate entities. However, it is known that some of these thrombus characteristics are strongly related. Multicollinearity can lead to unreliable prediction models. We aimed to determine the distribution, correlation and clustering of thrombus imaging characteristics based on a large dataset of anterior-circulation acute ischemic stroke patients.METHODS: We measured thrombus imaging characteristics in the MR CLEAN Registry dataset, which included occlusion location, distance from the intracranial carotid artery to the thrombus (DT), thrombus length, density, perviousness, and clot burden score (CBS). We assessed intercorrelations with Spearman's coefficient (ρ) and grouped thrombi based on 1) occlusion location and 2) thrombus length, density and perviousness using unsupervised clustering.RESULTS: We included 934 patients, of which 22% had an internal carotid artery (ICA) occlusion, 61% M1, 16% M2, and 1% another occlusion location. All thrombus characteristics were significantly correlated. Higher CBS was strongly correlated with longer DT (ρ=0.67, p&lt;0.01), and moderately correlated with shorter thrombus length (ρ=-0.41, p&lt;0.01). In more proximal occlusion locations, thrombi were significantly longer, denser, and less pervious. Unsupervised clustering analysis resulted in four thrombus groups; however, the cohesion within and distinction between the groups were weak.CONCLUSIONS: Thrombus imaging characteristics are significantly intercorrelated - strong correlations should be considered in future predictive modeling studies. Clustering analysis showed there are no distinct thrombus archetypes - novel treatments should consider this thrombus variability.</p

Clinical and Imaging Markers Associated With Hemorrhagic Transformation in Patients With Acute Ischemic Stroke

Item does not contain fulltex

Hemorrhage rates in patients with acute ischemic stroke treated with intravenous alteplase and thrombectomy versus thrombectomy alone

BACKGROUND: Intravenous alteplase treatment (IVT) for acute ischemic stroke carries a risk of intracranial hemorrhage (ICH). However, reperfusion of an occluded vessel itself may contribute to the risk of ICH. We determined whether IVT and reperfusion are associated with ICH or its volume in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN)-NO IV trial.METHODS: The MR CLEAN-NO IV trial randomized patients with acute ischemic stroke due to large vessel occlusion to receive either IVT followed by endovascular treatment (EVT) or EVT alone. ICH was classified according to the Heidelberg bleeding classification on follow-up MRI or CT approximately 8 hours-7 days after stroke. Hemorrhage volume was measured with ITK-snap. Successful reperfusion was defined as extended Thrombolysis In Cerebral Infarction (eTICI) score of 2b-3. Multinomial and binary adjusted logistic regression were used to determine the association of IVT and reperfusion with ICH subtypes.RESULTS: Of 539 included patients, 173 (32%) developed ICH and 30 suffered from symptomatic ICH (sICH) (6%). Of the patients with ICH, 102 had hemorrhagic infarction, 47 had parenchymal hematoma, 44 had SAH, and six had other ICH. Reperfusion was associated with a decreased risk of SAH, and IVT was not associated with SAH (eTICI 2b-3: adjusted OR 0.45, 95% CI 0.21 to 0.97; EVT without IVT: OR 1.6, 95% CI 0.91 to 2.8). Reperfusion status and IVT were not associated with overall ICH, hemorrhage volume, and sICH (sICH: EVT without IVT, OR 0.96, 95% CI 0.41 to 2.25; eTICI 2b-3, OR 0.49, 95% CI 0.23 to 1.05).CONCLUSION: Neither IVT administration before EVT nor successful reperfusion after EVT were associated with ICH, hemorrhage volume, and sICH. SAH occurred more often in patients for whom successful reperfusion was not achieved.</p

Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment: A Retrospective Cohort Study

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16-2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/; Unique identifier: ISRCTN10888758

Timing of symptomatic intracranial hemorrhage after endovascular stroke treatment

Introduction: Little is known about the timing of occurrence of symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) for acute ischemic stroke. A better understanding could optimize in-hospital surveillance time points and duration. The aim of this study was to delineate the probability of sICH over time and to identify factors associated with its timing. Patients and methods: We retrospectively analyzed data from the Dutch MR CLEAN trial and MR CLEAN Registry. We included adult patients who underwent EVT for an anterior circulation large vessel occlusion within 6.5 h of stroke onset. In patients with sICH (defined as ICH causing an increase of ⩾4 points on the National Institutes of Health Stroke Scale [NIHSS]), univariable and multivariable linear regression analysis was used to identify factors associated with the timing of sICH. This was defined as the time between end of EVT and the time of first CT-scan on which ICH was seen as a proxy. Results: SICH occurred in 205 (6%) of 3391 included patients. Median time from end of EVT procedure to sICH detection on NCCT was 9.0 [IQR 2.9–22.5] hours, with a rapidly decreasing incidence after 24 h. None of the analyzed factors, including baseline NIHSS, intravenous alteplase treatment, and poor reperfusion at the end of the procedure were associated with the timing of sICH. Conclusion: SICHs primarily occur in the first hours after EVT, and less frequently beyond 24 h. Guidelines that recommend to perform frequent neurological assessments for at least 24 h after intravenous alteplase treatment can be applied to ischemic stroke patients treated with EVT