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Cerebrovascular Reactivity Measurements in Patients with Aneurysmal Subarachnoid Hemorrhage: From Idea to Implementation
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-1668-2021
2026 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke associated with high mortality and morbidity. Although neurocritical care has improved over recent decades, delayed cerebral ischemia (DCI) remains a common yet difficult-to-predict complication with current clinical tools. Affecting approximately 30% of patients, it contributes substantially to poor outcome.

The aim of this thesis is to investigate cerebrovascular reactivity (CVR) as a method for assessing cerebral blood flow regulation and identifying patients at risk of ischemic complications after aSAH.

To enable studies across the full patient population, a novel method for controlled carbon dioxide challenges during both mechanical ventilation and spontaneous breathing was developed and applied in subsequent work. CVR measured with magnetic resonance imaging was evaluated in healthy volunteers to systematically investigate methodological factors affecting repeatability. Finally, CVR was assessed using transcranial Doppler ultrasound and magnetic resonance imaging in patients with aSAH to evaluate feasibility, safety, and potential clinical utility.

The developed system for controlled carbon dioxide challenges proved reliable and robust in achieving predefined stimulus levels during both mechanical ventilation and spontaneous breathing. Several important methodological considerations affecting the performance and interpretation of CVR measurements were identified. Magnetic resonance-based CVR using controlled inspired carbon dioxide was shown to be feasible in sedated and mechanically ventilated patients with aSAH. Preliminary results further suggest that CVR measurements may allow monitoring of ischemic evolution and early detection of DCI following aSAH.

By developing a method for controlled carbon dioxide challenges in mechanically ventilated patients, this work enables CVR investigations in previously understudied patient populations beyond aSAH. The systematic methodological investigations also contribute to greater transparency and standardization within the field. Although the clinical utility of CVR for risk stratification after aSAH could not be fully established, this thesis provides a methodological framework for future studies.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2026. , p. 80
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 2032
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:liu:diva-222398DOI: 10.3384/9789181184709ISBN: 9789181184693 (print)ISBN: 9789181184709 (electronic)OAI: oai:DiVA.org:liu-222398DiVA, id: diva2:2049512
Public defence
2026-04-29, Granitsalen, Building 440, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2026-03-30 Created: 2026-03-30 Last updated: 2026-03-30Bibliographically approved
List of papers
1. High inspired CO2 target accuracy in mechanical ventilation and spontaneous breathing using the Additional CO2 method
Open this publication in new window or tab >>High inspired CO2 target accuracy in mechanical ventilation and spontaneous breathing using the Additional CO2 method
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2024 (English)In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 11, article id 1352012Article in journal (Refereed) Published
Abstract [en]

Introduction Cerebrovascular reactivity imaging (CVR) is a diagnostic method for assessment of alterations in cerebral blood flow in response to a controlled vascular stimulus. The principal utility is the capacity to evaluate the cerebrovascular reserve, thereby elucidating autoregulatory functioning. In CVR, CO2 gas challenge is the most prevalent method, which elicits a vascular response by alterations in inspired CO2 concentrations. While several systems have been proposed in the literature, only a limited number have been devised to operate in tandem with mechanical ventilation, thus constraining the majority CVR investigations to spontaneously breathing individuals. Methods We have developed a new method, denoted Additional CO2, designed to enable CO2 challenge in ventilators. The central idea is the introduction of an additional flow of highly concentrated CO2 into the respiratory circuit, as opposed to administration of the entire gas mixture from a reservoir. By monitoring the main respiratory gas flow emanating from the ventilator, the CO2 concentration in the inspired gas can be manipulated by adjusting the proportion of additional CO2. We evaluated the efficacy of this approach in (1) a ventilator coupled with a test lung and (2) in spontaneously breathing healthy subjects. The method was evaluated by assessment of the precision in attaining target inspired CO2 levels and examination of its performance within a magnetic resonance imaging environment. Results and discussion Our investigations revealed that the Additional CO2 method consistently achieved a high degree of accuracy in reaching target inspired CO2 levels in both mechanical ventilation and spontaneous breathing. We anticipate that these findings will lay the groundwork for a broader implementation of CVR assessments in mechanically ventilated patients.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2024
Keywords
cerebrovascular reactivity; CO2 gas challenge; ventilation; magnetic resonance imaging; carbon dioxide; vascular stimulus
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:liu:diva-205177 (URN)10.3389/fmed.2024.1352012 (DOI)001238787800001 ()38841571 (PubMedID)2-s2.0-85195056280 (Scopus ID)
Note

Funding Agencies|Swedish Research Council [2022-02886, 2018-05418, 2018-03319, 2023-03186, 2023-05460]; Swedish Brain Foundation [FO2022-0109]; Region OEstergoetland (ALF grant); EU [101080875, 777107]

Available from: 2024-06-20 Created: 2024-06-20 Last updated: 2026-03-30

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Magnusson, Gustav

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2627282930313229 of 75
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