Impact of helium-oxygen inhalation on ventilation, blood oxygenation, and aerosol deposition in chronic obstructive respiratory diseases: asthma and emphysema
This project deals with the use of helium/oxygen mixtures in therapies of chronic obstructive diseases such as asthma and COPD (in particular, emphysema). The global objective is to investigate the use of helium-oxygen mixtures in these diseases by characterising ventilation parameters (gas flow distribution, work of breathing), oxygen alveolar transfer in the blood, and penetration depth of aerosolised drug in the airways, in order to demonstrate the benefits for the patient of helium-oxygen compared to air.
The first part of the project will consist of a pre-clinical study. The animal model (rat) will be declined in three states: healthy, asthma model, and emphysema model.
The pre-clinical study will include two phases: 1. Analysis of ventilation, work of breathing and oxygen transfer through alveolar membrane, and 2. Study of aerosol transport and deposition. The ventilation distribution will be analyzed using two complementary techniques: hyperpolarised helium-3 MRI, and krypton ventilation scintigraphy. The aerosol deposition study will consist in aerosol administration to the rat using a nebulisation system previously developed, followed by images acquisition by two high performance techniques: hyperpolarised helium-3 MRI, and 3D CT-SPECT. For both the ventilation and the aerosol studies, the effect of the gas (air vs. helium/oxygen) in the animal models (healthy, emphysema and asthmatic) will be compared. This pre-clinical part may show the benefits of helium/oxygen in terms of work of breathing, oxygen transfer, and regional aerosol deposition.
The second part of this project will be in silico simulations. For this part, the morphology of both healthy and pathological rat airways will be characterised using Micro-CT Scan imaging, aiming at reconstructing numerically this morphology in 3D. A complete theoretical model of bronchial tract will be obtained, whose first generations will come from this 3D reconstruction and the following ones from morphometric models available in the literature. Many theoretical models of ventilation and aerosol deposition prediction in airways can be found in the literature, but very few of them consider pathological morphology. Therefore we will develop improved analytical/numerical models taking into account pathological characteristics and asymmetry of the airways based on the 3D reconstructed morphology. These models will also focus on work of breathing and alveolo-capillary oxygen transfer. They should allow transposing the simulation results of ventilation and drug deposition in a pathological respiratory tract to the human case.
An in vitro study will also focus on aerosol behavior in simplified models of rat airways singularities to validate the in silico models. Comparison between the simulations performed with these models and in vivo / in vitro experiments should validate the models.
Finally, in the third part of the project, the results that will have been obtained in the previous phases will allow setting up a clinical study on ventilation in humans with hyperpolarised helium-3 MRI. This clinical study may demonstrate the ability of these models to predict ventilation distribution according to the pathological characteristics of the patient.