Periodic Reporting for period 1 - V-LF-Spiro3D (Low and very-low-field 3D magnetic resonance spirometry for advanced regional exploration of respiratory diseases)
Reporting period: 2023-04-01 to 2024-03-31
Lung function is a central concern in the fight against covid-19. Beyond the pandemic heavy losses and long-term health implications, respiratory diseases represent a major threat for the World Health Organisation. It is one of the leading causes of death worldwide, associated to our way of living and impacting all of society. Current tools for diagnosing and monitoring pulmonary conditions are hindered by poor sensitivity (lung function tests), radiation exposure (computed tomography) or examination cost (magnetic resonance imaging, MRI). They all differently fail to fully assess lung structure and function.
V|LF-Spiro3D aims at democratizing newly developed and breakthrough 3D MR spirometry with high performance, low-cost MRI techniques to provide a ten-minute morphofunctional MRI protocol to engage patients in a safer, easier and more comfortable way.
Based on recent works at Universities Paris-Saclay and Aberdeen, in collaboration with leading MR manufacturer Siemens, SME NMR Service, major French-Dutch hospitals and patient organisations, V|LF-Spiro3D brings together multidisciplinary experts in a patient-oriented approach for both adults and children.
V|LF-Spiro3D is redesigning current MRI architecture to perform 3D MR spirometry at low and very low field. High-performance MRI hardware is being developed with accelerated acquisitions and coupled reconstruction strategies relying on deep learning. Biomechanical lung modelling and deep data processing are being designed following the implementation of 3D MR spirometry in clinical facilities to produce unprecedentedly large sets of normative and training data covering six major respiratory diseases.
By prioritizing both technology transfer and innovation, V|LF-Spiro3D aims to build up a one-stop-shop imaging standard for unrestricted assessment of lung pathophysiology. The impacts are expected to yield benefits beyond lung imaging and boost health deep-tech on point-of-care imaging and multi-parameter-based digital health in the EU.
V|LF-Spiro3D aims at democratizing newly developed and breakthrough 3D MR spirometry with high performance, low-cost MRI techniques to provide a ten-minute morphofunctional MRI protocol to engage patients in a safer, easier and more comfortable way.
Based on recent works at Universities Paris-Saclay and Aberdeen, in collaboration with leading MR manufacturer Siemens, SME NMR Service, major French-Dutch hospitals and patient organisations, V|LF-Spiro3D brings together multidisciplinary experts in a patient-oriented approach for both adults and children.
V|LF-Spiro3D is redesigning current MRI architecture to perform 3D MR spirometry at low and very low field. High-performance MRI hardware is being developed with accelerated acquisitions and coupled reconstruction strategies relying on deep learning. Biomechanical lung modelling and deep data processing are being designed following the implementation of 3D MR spirometry in clinical facilities to produce unprecedentedly large sets of normative and training data covering six major respiratory diseases.
By prioritizing both technology transfer and innovation, V|LF-Spiro3D aims to build up a one-stop-shop imaging standard for unrestricted assessment of lung pathophysiology. The impacts are expected to yield benefits beyond lung imaging and boost health deep-tech on point-of-care imaging and multi-parameter-based digital health in the EU.
The main goal of V|LF-Spiro3D is to create and validate a new way to view and understand the 3D structure and function of the lungs using affordable and compact V|LF-MRI technology. This scientific and technological breakthrough aims to provide an accessible tool for the early diagnosis, staging, and treatment follow-up of respiratory diseases.
V|LF-Spiro3D focuses on:
1. Producing standard 3D MR spirometry data.
2. Developing a post-processing workflow for 3D MR spirometry.
3. Developing methodologies and instruments for low- and very-low-field 3D MR spirometry.
4. Studying the impact of 3D MR spirometry on patients' experiences, clinical communication, and cultural perceptions.
In the first year, the project has made significant progress, including:
¨ Initial implementation of the technique on GE Healthcare and Siemens MR and PET-MR hybrid systems.
¨ An exploratory clinical trial involving 25 healthy adult volunteers.
¨ Preliminary findings on new biomechanical biomarkers.
¨ Development of an efficient workflow for data reconstruction and processing.
¨ Creation of new RF coil arrays and preamplifiers for very-low-field MRI.
¨ Establishment of a social and humanistic study plan with open questionnaires.
¨ Initiation of a behavioural art-science project.
V|LF-Spiro3D kicked-off on February 6-7, 2023 before starting on April 1st, 2023. An undergraduate student, 6 master interns, 2 early stage engineers, 7 early stage researchers (4 PhD students, 3 post-doctoral fellows), and a project manager have been involved and recruited so far in V|LF-Spiro3D. Five more early stage researchers (3 PhD students, 2 post-doctoral fellows) are about to integrate the consortium.
From January 2024 on, scientific dissemination among partners have been enforced by monthly interdisciplinary seminars while online and offline bilateral or multilateral meetings have been set up to design a first low-field road map and test a first MR-compatible spirometer prototype, build integrative research protocols, establish global ethics, and implement 3D MR spirometry at two out of the four clinical partner sites while already closing a preliminary study on 25 healthy adult volunteers and running the first arm with reversibility challenge in adult asthma and chronic obstructive pulmonary disease (COPD). The integrated research protocols on adults at standard field have been approved by the Institutional Review Board (IRB) together with three ancillary studies on (1) the objectivation and acceptance of 3D MR spirometry (2) the alternative phase-resolved functional lung (PREFUL) MRI, and (3) the related 4D flow MRI in the aorta. The integrated research protocols on children at standard field have been submitted and approval is expected very soon.
Three-dimensional MR spirometry basic reconstruction has been secured, validated, and improved (repeatability, reproducibility, robustness) on 25 female and male adult healthy volunteers (101 datasets) with proven sensitivity to gravity dependence. It is being improved to include deep segmentation at the lobar level, absolute time local registration, 4D parametric maps, and biomechanical modelling.
V|LF-Spiro3D focuses on:
1. Producing standard 3D MR spirometry data.
2. Developing a post-processing workflow for 3D MR spirometry.
3. Developing methodologies and instruments for low- and very-low-field 3D MR spirometry.
4. Studying the impact of 3D MR spirometry on patients' experiences, clinical communication, and cultural perceptions.
In the first year, the project has made significant progress, including:
¨ Initial implementation of the technique on GE Healthcare and Siemens MR and PET-MR hybrid systems.
¨ An exploratory clinical trial involving 25 healthy adult volunteers.
¨ Preliminary findings on new biomechanical biomarkers.
¨ Development of an efficient workflow for data reconstruction and processing.
¨ Creation of new RF coil arrays and preamplifiers for very-low-field MRI.
¨ Establishment of a social and humanistic study plan with open questionnaires.
¨ Initiation of a behavioural art-science project.
V|LF-Spiro3D kicked-off on February 6-7, 2023 before starting on April 1st, 2023. An undergraduate student, 6 master interns, 2 early stage engineers, 7 early stage researchers (4 PhD students, 3 post-doctoral fellows), and a project manager have been involved and recruited so far in V|LF-Spiro3D. Five more early stage researchers (3 PhD students, 2 post-doctoral fellows) are about to integrate the consortium.
From January 2024 on, scientific dissemination among partners have been enforced by monthly interdisciplinary seminars while online and offline bilateral or multilateral meetings have been set up to design a first low-field road map and test a first MR-compatible spirometer prototype, build integrative research protocols, establish global ethics, and implement 3D MR spirometry at two out of the four clinical partner sites while already closing a preliminary study on 25 healthy adult volunteers and running the first arm with reversibility challenge in adult asthma and chronic obstructive pulmonary disease (COPD). The integrated research protocols on adults at standard field have been approved by the Institutional Review Board (IRB) together with three ancillary studies on (1) the objectivation and acceptance of 3D MR spirometry (2) the alternative phase-resolved functional lung (PREFUL) MRI, and (3) the related 4D flow MRI in the aorta. The integrated research protocols on children at standard field have been submitted and approval is expected very soon.
Three-dimensional MR spirometry basic reconstruction has been secured, validated, and improved (repeatability, reproducibility, robustness) on 25 female and male adult healthy volunteers (101 datasets) with proven sensitivity to gravity dependence. It is being improved to include deep segmentation at the lobar level, absolute time local registration, 4D parametric maps, and biomechanical modelling.
The 3D MR spirometry workflow developed by V|LF-Spiro3D has introduced several innovative features:
(1) New biomechanical biomarkers along normal strains.
(2) An original phase-portrait retrospective gating method for 3D lung dynamic MRI data.
(3) An automatic deep segmentation scheme.
(4) A semi-automatic vessel-based lobar segmentation of the lung.
These advancements have been published, though the core processing algorithm remains undisclosed. These developments establish 3D MR spirometry as a robust tool for assessing lung function and have potential applications in other lung MRI techniques. However, these are preliminary steps, and further work is needed:
(1) Additional data from healthy and diseased subjects are required to support understanding and interpretation, as current data are limited to three acquisitions in a single healthy volunteer.
(2) The new gating method should be compared with traditional amplitude-time retrospective gating to quantify improvements.
(3) The deep segmentation method could be improved with more training data and should be tested on patient data.
(4) Automation and robustness of the segmentation should be tested in project cohorts.
On the hardware side, the developments pave the way for very low-field (VLF) 3D MR spirometry and more generally, VLF MRI. These components are the first steps toward creating an affordable, low-field MRI system. Further research is needed to optimize the design of RF coils, MR sequences, reconstruction strategies, and analysis methods. Each component will be demonstrated and refined throughout the project.
(1) New biomechanical biomarkers along normal strains.
(2) An original phase-portrait retrospective gating method for 3D lung dynamic MRI data.
(3) An automatic deep segmentation scheme.
(4) A semi-automatic vessel-based lobar segmentation of the lung.
These advancements have been published, though the core processing algorithm remains undisclosed. These developments establish 3D MR spirometry as a robust tool for assessing lung function and have potential applications in other lung MRI techniques. However, these are preliminary steps, and further work is needed:
(1) Additional data from healthy and diseased subjects are required to support understanding and interpretation, as current data are limited to three acquisitions in a single healthy volunteer.
(2) The new gating method should be compared with traditional amplitude-time retrospective gating to quantify improvements.
(3) The deep segmentation method could be improved with more training data and should be tested on patient data.
(4) Automation and robustness of the segmentation should be tested in project cohorts.
On the hardware side, the developments pave the way for very low-field (VLF) 3D MR spirometry and more generally, VLF MRI. These components are the first steps toward creating an affordable, low-field MRI system. Further research is needed to optimize the design of RF coils, MR sequences, reconstruction strategies, and analysis methods. Each component will be demonstrated and refined throughout the project.