scholarly journals Treatment Efficacy Analysis in Acute Ischemic Stroke Patients Using In Silico Modeling Based on Machine Learning: A Proof-of-Principle

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1357
Author(s):  
Anthony Winder ◽  
Matthias Wilms ◽  
Jens Fiehler ◽  
Nils D. Forkert

Interventional neuroradiology is characterized by engineering- and experience-driven device development with design improvements every few months. However, clinical validation of these new devices requires lengthy and expensive randomized controlled trials. This contribution proposes a machine learning-based in silico study design to evaluate new devices more quickly with a small sample size. Acute diffusion- and perfusion-weighted MRI, segmented one-week follow-up imaging, and clinical variables were available for 90 acute ischemic stroke patients. Three treatment option-specific random forest models were trained to predict the one-week follow-up lesion segmentation for (1) patients successfully recanalized using intra-arterial mechanical thrombectomy, (2) patients successfully recanalized using intravenous thrombolysis, and (3) non-recanalizing patients as an analogue for conservative treatment for each patient in the sample, independent of the true group membership. A repeated-measures analysis of the three predicted follow-up lesions for each patient revealed significantly larger lesions for the non-recanalizing group compared to the successful intravenous thrombolysis treatment group, which in turn showed significantly larger lesions compared to the successful mechanical thrombectomy treatment group (p < 0.001). A groupwise comparison of the true follow-up lesions for the three treatment options showed the same trend but did not reach statistical significance (p = 0.19). We conclude that the proposed machine learning-based in silico trial design leads to clinically feasible results and can support new efficacy studies by providing additional power and potential early intermediate results.

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Tan Xu ◽  
Yonghong Zhang ◽  
Yingxian Sun ◽  
Chung-Shiuan Chen ◽  
Jing Chen ◽  
...  

Introduction: The effects of blood pressure (BP) reduction on clinical outcomes among acute stroke patient remain uncertain. Hypothesis: We tested the effects of immediate BP reduction on death and major disability at 14 days or hospital discharge and 3-month follow-up in acute ischemic stroke patients with and without a previous history of hypertension or use of antihypertensive medications. Methods: The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) randomly assigned patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP) to receive antihypertensive treatment (N=2,038) or to discontinue all antihypertensive medications (N=2,033) during hospitalization. Randomization was stratified by participating hospitals and use of antihypertensive medications. Study outcomes were assessed at 14 days or hospital discharge and 3-month post-treatment follow-up. The primary outcome was death and major disability (modified Rankin Scale score≥3), and secondary outcomes included recurrent stroke and vascular events. Results: Mean SBP was reduced 12.7% in the treatment group and 7.2% in the control group within 24 hours after randomization (P<0.001). Mean SBP was 137.3 mmHg in the treatment group and 146.5 in the control group at day 7 after randomization (P<0.001). At 14 days or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups by subgroups. At the 3-month follow-up, recurrent stroke was significantly reduced in the antihypertensive treatment group among patients with a history of hypertension (odds ratio 0.43, 95% CI 0.24-0.75, P=0.003) and among patients with a history of use of antihypertensive medications (odds ratio 0.41, 95% CI 0.20-0.84, P=0.01). All-cause mortality (odds ratio 2.84, 95% CI 1.11-7.27, P=0.03) was increased among patients without a history of hypertension. Conclusion: Immediate BP reduction lowers recurrent stroke among acute ischemic stroke patients with a previous history of hypertension or use of antihypertensive medications at 3 months. On the other hand, BP reduction increases all-cause mortality among patients without a history of hypertension.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sarah R Martha ◽  
Qiang Cheng ◽  
Liyu Gong ◽  
Lisa Collier ◽  
Stephanie Davis ◽  
...  

Background and Purpose: The ability to predict ischemic stroke outcomes in the first day of admission could be vital for patient counseling, rehabilitation, and care planning. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) collects blood samples distal and proximal to the intracranial thrombus during mechanical thrombectomy. These samples are a novel resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and patient demographics that are predictive of stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients. Methods: The BACTRAC study is a non-probability, convenience sampling of subjects (≥ 18 year olds) treated with mechanical thrombectomy for emergent large vessel occlusion. We evaluated relative concentrations of mRNA for gene expression in 84 inflammatory molecules in static blood distal and proximal to the intracranial thrombus from adults who underwent thrombectomy. We employed a machine learning method, Random Forest, utilizing the first set of enrolled subjects, to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes. Results: We analyzed the first 28 subjects (age = 66 ± 15.48, 11 males) in the BACTRAC registry. Results from machine learning analyses demonstrate that the genes CCR4, IFNA2, IL9, CXCL3, Age, DM, IL7, CCL4, BMI, IL5, CCR3, TNF, and IL27 predict infarct volume. The genes IFNA2, IL5, CCL11, IL17C, CCR4, IL9, IL7, CCR3, IL27, DM, and CSF2 predict edema volume. There is an intersection of genes CCR4, IFNA2, IL9, IL7, IL5, CCR3 to both infarct and edema volumes. Overall, these genes depicts a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils. Conclusions: Machine learning algorithms can be employed to develop predictive biomarker signatures for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.


2020 ◽  
pp. neurintsurg-2020-015966 ◽  
Author(s):  
Ryan A Rava ◽  
Kenneth V Snyder ◽  
Maxim Mokin ◽  
Muhammad Waqas ◽  
Xiaoliang Zhang ◽  
...  

BackgroundCT perfusion (CTP) infarct and penumbra estimations determine the eligibility of patients with acute ischemic stroke (AIS) for endovascular intervention. This study aimed to determine volumetric and spatial agreement of predicted RAPID, Vitrea, and Sphere CTP infarct with follow-up fluid attenuation inversion recovery (FLAIR) MRI infarct.Methods108 consecutive patients with AIS and large vessel occlusion were included in the study between April 2019 and January 2020 . Patients were divided into two groups: endovascular intervention (n=58) and conservative treatment (n=50). Intervention patients were treated with mechanical thrombectomy and achieved successful reperfusion (Thrombolysis in Cerebral Infarction 2b/2 c/3) while patients in the conservative treatment group did not receive mechanical thrombectomy or intravenous thrombolysis. Intervention and conservative treatment patients were included to assess infarct and penumbra estimations, respectively. It was assumed that in all patients treated conservatively, penumbra converted to infarct. CTP infarct and penumbra volumes were segmented from RAPID, Vitrea, and Sphere to assess volumetric and spatial agreement with follow-up FLAIR MRI.ResultsMean infarct differences (95% CIs) between each CTP software and FLAIR MRI for each cohort were: intervention cohort: RAPID=9.0±7.7 mL, Sphere=−0.2±8.7 mL, Vitrea=−7.9±8.9 mL; conservative treatment cohort: RAPID=−31.9±21.6 mL, Sphere=−26.8±17.4 mL, Vitrea=−15.3±13.7 mL. Overlap and Dice coefficients for predicted infarct were (overlap, Dice): intervention cohort: RAPID=(0.57, 0.44), Sphere=(0.68, 0.60), Vitrea=(0.70, 0.60); conservative treatment cohort: RAPID=(0.71, 0.56), Sphere=(0.73, 0.60), Vitrea=(0.72, 0.64).ConclusionsSphere proved the most accurate in patients who had intervention infarct assessment as Vitrea and RAPID overestimated and underestimated infarct, respectively. Vitrea proved the most accurate in penumbra assessment for patients treated conservatively although all software overestimated penumbra.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoting Ma ◽  
Shuo Li ◽  
Baixue Jia ◽  
Dapeng Mo ◽  
Ning Ma ◽  
...  

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p &gt; 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy.


Author(s):  
Rosanna Rossi ◽  
Seán Fitzgerald ◽  
Sara Molina ◽  
Oana Madalina Mereuta ◽  
Andrew Douglas ◽  
...  

Abstract Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal–Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shon Thomas ◽  
Paula De La Pena ◽  
Liam Butler ◽  
Oguz Akbilgic ◽  
Daniel Heiferman ◽  
...  

Background and Purpose: Early identification of large vessel occlusions (LVO) and timely recanalization are paramount in improved clinical outcomes in acute ischemic stroke. Multiple simple stroke scales have good sensitivity, but compromise specificity for predicting LVO. No scale has been shown to predict mechanical thrombectomy (MT) candidacy. Machine learning techniques are being used for predictive modeling in many aspects of stroke care and may have potential in predicting LVO presence and MT candidacy. Methods: 287 acute ischemic stroke patients from July 2018 to July 2019 at Loyola University Medical Center were included. 36 clinical and demographic variables were analyzed using machine learning and statistical algorithms, including logistic regression, extreme gradient boosting, random forest, and decision trees to build models predictive of LVO and MT. The best performing model was compared with prior stroke scales. Results: Random forest based model resulted in the highest classification performance to predict both LVO and MT outcomes with an area under the curve (AUC) of 0.90±0.07 and 0.94±0.04, respectively. When the predictors were reduced to 7, random forest maintained a high AUC for predicting LVO (0.89). When reduced to 10 predictors, the random forest model predicted MT with an AUC = 0.93. Random forest models had excellent sensitivity and specificity of 0.86 and 0.89 for LVO and 0.89 and 0.95 for MT, respectively. The negative predictive value was 0.94 for LVO and 0.98 for MT while the positive predictive value was 0.77 for LVO and 0.79 for MT. With equal sensitivity, the random forest model was favorable to all previous stroke scales. Conclusion: Machine learning utilizing clinical and demographic variables predicts LVO and patient candidacy for MT with a high degree of accuracy. Further validation of this strategy for triage of stroke patients requires prospective and external validation.


2020 ◽  
Author(s):  
Henry Horng-Shing Lu ◽  
Chi-Ling Kao ◽  
Chih-Ming Lin ◽  
Shu-Wei Chang ◽  
Chi-Kuang Liu ◽  
...  

Abstract Background The treatment of acute ischemic stroke is heavily time-dependent, and even though, with the most efficient treatment, the long-term functional outcome is still highly variable. In this current study, the authors selected acute ischemic stroke patients who were qualified for intravenous thrombolysis with recombinant tissue plasminogen activator and followed by intra-arterial thrombectomy. With primary outcome defined by the functional level in a one-year follow-up, we hypothesize that patients with older age are at a disadvantage in post-stroke recovery. However, an age-threshold should be determined to help clinicians in selection of patients to undergo such therapy. Methods This is a retrospective chart review study that include 92 stroke patients in Changhua Christian hospital with a total of 68 evaluation indexes recorded. The current study utilized the forward stepwise regression model whose Adj-R2 and p-value in search of important variables for outcome prediction. The chngpt package in R indicated the threshold point of the age factor directing the better future functionality of the stroke patients. Results Datasets revealed the threshold of the age set at 79 the most appropriate. Admission Barthel Index, Age, Ipsi ICA RI, Ipsi VA PI, Contra MCA stenosis, Contra ECA RI, and in-hospital pneumonia are the significant predicting variables. The higher the age, in-hospital pneumonia, Contra MCA stenosis, Ipsi ICA RI and Ipsi VA PI, the less likely patient to recover from functional deficits as the result of acute ischemic stroke; the higher the value of Contra ECA RI and Admission Barthel Index, the better chance to recover at one-year follow up. Conclusions Parameters of pre-intervention datasets could provide important information to aid first-line clinicians in decision making. Especially, in patients whose age is above seventy-nine receives diminish return in the benefit to undergo such intervention and should be considered seriously by both the patients and the physicians.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yukiko Enomoto ◽  
Shinichi Yoshimura ◽  
Yusuke Egashira ◽  
Toru Iwama

Objectives: Endovascular treatment provides a therapeutic option for acute ischemic stroke patients who are ineligible for, or who do not respond to intravenous thrombolysis. Higher rates of recanalization by mechanical clot extraction device were reportedly associated with better clinical outcome, but the long-term patency of recanalized vessel is unknown. Methods: We retrospectively evaluated magnetic resonance angiography (MRA) at 24-hour and 3-month after the endovascular treatment in consecutive acute stroke patients who were treated with mechanical clot extraction device between Oct. 2010 and May 2012 in our institution. Results: Fourty-six patients received endovascular treatment for acute ischemic stroke and 35 were treated with mechanical clot extraction devices, Merci and/or Penumbra system, with or without adjunctive therapy. Mean age was 69±12 years, baseline median National Institutes of Health Stroke Scale score was 15 (8 to 24), and occluded vessels were the internal carotid artery in 34%, middle cerebral artery (MCA) in 54%, and vertebro-basilar artery in 11%. Successful recanalization, defined as Thrombolysis In Myocardial Infarction II or III perfusion, was obtained in 32 (91%) patients. During 24-hour after the treatment, reocclusion of the treated vessel was observed in 4 (12.5%) patients. Of 28 eligible patients, 21 (75%) patients had 3-month MRA follow-up. None of the patients had reocclusion, but clinically silent diffuse stenosis was observed in 2 (9.5%) patients. Statistically significant predictors were not identified, but both of the patients were MCA occlusion treated with Merci retriever. Conclusion: In this study, late stenosis was observed in the MCA on 3-month follow-up MRA. Long-term follow-up seems to be useful to follow the recanalized vessels, especialy when mechanical devices were used.


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