Artificial intelligence and cost-effectiveness analyses of radiological imaging in acute ischemic stroke

Acute ischemic stroke is caused by an occlusion of an artery in the brain. Current treatment options for acute ischemic stroke are intravenous thrombolysis and endovascular treatment. In this thesis, three parts describe varying analytical approaches to improve acute stroke care. Part I provides model-based health economic analyses of treatment decisions to improve acute stroke care. Specifically, the benefits of expedited endovascular treatment delivery and the use of CT perfusion for patient selection and occlusion detection are described. In Part II, prognostic imaging markers are studied. Deep learning-based quantification of white matter lesion volume in CT is compared to the radiologist-lead Fazekas scale for prognosticating functional outcome and intracranial hemorrhage occurrence. We studied if intravenous thrombolysis before endovascular treatment might be withheld based on increased risks for poor outcome and intracranial hemorrhage related to white matter lesion load. Furthermore, we evaluated thrombus volume, thrombus length, and thrombus radiomics as patient functional and endovascular treatment procedural outcome predictors. In Part III, we used generative adversarial networks to perform image-to-image translation. We translated CT scans with follow-up hemorrhagic or ischemic stroke lesions to baseline CT scans without. Furthermore, we remove contrast in CTA by translating a CTA to a non-contrast CT. Based on these translations we extract lesion segmentations in follow-up CT and vessel segmentations in CTA

Modeling of mode-locking in a laser with spatially separate gain media

We present a novel laser mode-locking scheme and discuss its unusual properties and feasibility using a theoretical model. A large set of single-frequency continuous-wave lasers oscillate by amplification in spatially separated gain media. They are mutually phase-locked by nonlinear feedback from a common saturable absorber. As a result, ultra short pulses are generated. The new scheme offers three significant benefits: the light that is amplified in each medium is continuous wave, thereby avoiding issues related to group velocity dispersion and nonlinear effects that can perturb the pulse shape. The set of frequencies on which the laser oscillates, and therefore the pulse repetition rate, is controlled by the geometry of resonator-internal optical elements, not by the cavity length. Finally, the bandwidth of the laser can be controlled by switching gain modules on and off. This scheme offers a route to mode-locked lasers with high average output power, repetition rates that can be scaled into the THz range, and a bandwidth that can be dynamically controlled. The approach is particularly suited for implementation using semiconductor diode laser arrays.Comment: 13 pages, 5 figures, submitted to Optics Expres

Cost-effectiveness of CT perfusion for the detection of large vessel occlusion acute ischemic stroke followed by endovascular treatment:a model-based health economic evaluation study

Objectives:CT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)–eligible occlusion detection using model-based analyses. Methods: In this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018–March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT + CTA + CTP) with a generated counterfactual where NCCT and CTA (NCCT + CTA) was used for LVO detection. The NCCT + CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (ΔQALY) and costs (ΔCosts) per LVO patient. Results: We included 701 patients (median age: 72, IQR: [62–81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (ΔCosts median: € − 2671, IQR: [€ − 4721; € − 731]), a health gain (ΔQALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient. Conclusion: CTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective. Clinical relevance statement.: Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective. Key Points: • Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up. • Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: € − 3857, IQR: [€ − 5907; € − 1916] per patient). • As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required.</p

Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands

BACKGROUND: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. METHODS: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. RESULTS: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. CONCLUSION: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs

Infarct evolution in patients with anterior circulation large-vessel occlusion randomized to IV alteplase and endovascular treatment versus endovascular treatment alone

BACKGROUND AND PURPOSE: Infarct evolution after endovascular treatment varies widely among patients with stroke and may be affected by baseline characteristics and procedural outcomes. Moreover, IV alteplase and endovascular treatment may influence the relationship of these factors to infarct evolution. We aimed to assess whether the infarct evolution between baseline and follow-up imaging was different for patients who received IVT and EVT versus EVT alone.MATERIALS AND METHODS: We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV trial with baseline CTP and follow-up imaging. Follow-up infarct volume was segmented on 24-hour or 1-week follow-up DWI or NCCT. Infarct evolution was defined as the follow-up lesion volume: CTP core volume. Substantial infarct growth was defined as an increase in follow-up infarct volume of >10?mL. We assessed whether infarct evolution was different for patients with IV alteplase and endovascular treatment versus endovascular treatment alone and evaluated the association of baseline characteristics and procedural outcomes with infarct evolution using multivariable regression.RESULTS: From 228 patients with CTP results available, 145 patients had follow-up imaging and were included in our analysis. For patients with IV alteplase and endovascular treatment versus endovascular treatment alone, the baseline median CTP core volume was 17 (interquartile range = 4-35) mL versus 11 (interquartile range = 6-24) mL. The median follow-up infarct volume was 13 (interquartile range, 4-48) mL versus 17 (interquartile range = 4-50) mL. Collateral status and occlusion location were negatively associated with substantial infarct growth in patients with and without IV alteplase before endovascular treatment.CONCLUSIONS: No statistically significant difference in infarct evolution was found in directly admitted patients who received IV alteplase and endovascular treatment within 4.5?hours of symptom onset versus patients who underwent endovascular treatment alone. Collateral status and occlusion location may be useful predictors of infarct evolution prognosis in patients eligible for IV alteplase who underwent endovascular treatment.Paroxysmal Cerebral Disorder

A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. METHODS We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. RESULTS The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). CONCLUSIONS In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups

Association between computed tomography perfusion and the effect of intravenous alteplase prior to endovascular treatment in acute ischemic stroke

PurposeIntravenous alteplase (IVT) prior to endovascular treatment (EVT) is neither superior nor noninferior to EVT alone in acute ischemic stroke patients. We aim to assess whether the effect of IVT prior to EVT differs according to CT perfusion (CTP)-based imaging parameters.MethodsIn this retrospective post hoc analysis, we included patients from the MR CLEAN-NO IV with available CTP data. CTP data were processed using syngo.via (version VB40). We performed multivariable logistic regression to obtain the effect size estimates (adjusted common odds ratio a[c]OR) on 90-day functional outcome (modified Rankin Scale [mRS]) and functional independence (mRS 0-2) for CTP parameters with two-way multiplicative interaction terms between IVT administration and the studied parameters.ResultsIn 227 patients, median CTP-estimated core volume was 13 (IQR 5-35) mL. The treatment effect of IVT prior to EVT on outcome was not altered by CTP-estimated ischemic core volume, penumbral volume, mismatch ratio, and presence of a target mismatch profile. None of the CTP parameters was significantly associated with functional outcome after adjusting for confounders.ConclusionIn directly admitted patients with limited CTP-estimated ischemic core volumes who presented within 4.5 h after symptom onset, CTP parameters did not statistically significantly alter the treatment effect of IVT prior to EVT. Further studies are needed to confirm these results in patients with larger core volumes and more unfavorable baseline perfusion profiles on CTP imaging.Paroxysmal Cerebral Disorder