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Theses

Imagerie fonctionnelle et quantitative des lésions pulmonaires induites par la ventilation mécanique sur poumons sains et agressés

Abstract : Ventilator-induced lung injuries encompasses the physical and inflammatory damage that the lungs experience when mechanical ventilation is administered, especially in the case of inadequate settings. Lung imaging with coupled positron emission tomography/computerized tomodensitometry (PET/CT) allows the in vivo assessment of these physical and biological processes, if an inflammation-specific PET radiotracer is selected. Our hypothesis was that coupled PET/CT using [11C](R)-PK11195 to specifically quantify macrophage recruitment would allow the quantification of the inflammatory response in relation with the ventilatory interventions applied to animals with or without experimental acute respiratory distress syndrome (ARDS). The assessment of the association of the inflammatory response with CT-measured parameters would the allow the translation of these concepts to the clinical setting. Our results show that: 1- the lung inflammatory response, as assessed by the lung standardized uptake value of [11C](R)-PK11195, as significantly increased in an experimental of high tidal volume VILI in animals with healthy lungs. Increased inflammation was associated with the intensity of dynamic strain and tidal hyperinflation measured in CT; 2- the PET quantification [11C](R)-PK11195 lung uptake was significantly improved by the use of a three-tissue compartment kinetic model, as compared to the conventional two-tissue compartment model. Of note, using this methodology, [11C](R)-PK11195 uptake quantification was made independent of the underlying lung density in the studied region; 3- [11C](R)-PK11195 lung uptake was significantly decreased in all lung regions of animals with experimental ARDS ventilated with protective ventilator settings in the prone position, as compared to animals in the supine position, in association with improved homogenization of regional lung aeration. Lung inflammation was independently associated with increased dynamic strain quantified in CT; 4- quantitative lung CT allowed the identification 2 specific CT phenotypes in individuals with COVID-19-associated ARDS, one comparable to non-COVID-19 ARDS (with decreased lung aeration and low respiratory system compliance) and the second showing a high proportion of normally aerated lung in line with low respiratory elastance. Our work shows the promising performance of [11C](R)-PK11195 to evaluate in vivo the inflammatory response to inadequate ventilatory settings. Its quantification in the lung was made more precise with the use of multi-tissue compartment kinetic models. Our results show that the inflammatory response is modulated by regional variations in the intensity of several mechanical injurious mechanisms, such as dynamic strain or tidal hyperinflation. Finally the clinical study demonstrates the potential of quantitative CT to guide ventilator settings adjustments, aiming to prevent or limit mechanical and biological injuries induced by mechanical ventilation.
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https://tel.archives-ouvertes.fr/tel-03703087
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Submitted on : Thursday, June 23, 2022 - 4:04:11 PM
Last modification on : Friday, June 24, 2022 - 11:17:07 AM

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  • HAL Id : tel-03703087, version 1

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Laurent Bitker. Imagerie fonctionnelle et quantitative des lésions pulmonaires induites par la ventilation mécanique sur poumons sains et agressés. Médecine humaine et pathologie. Université de Lyon, 2021. Français. ⟨NNT : 2021LYSE1274⟩. ⟨tel-03703087⟩

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