Periodic Reporting for period 2 - ImageInLife (Training European Experts in Multilevel Bioimaging, Analysis and Modelling of Vertebrate Development and Disease)
Période du rapport: 2019-01-01 au 2021-06-30
It is now possible to image complex biological processes not only within living animals but also within the human body to understand pathological situations and open the way to therapeutics.The main problem is to adapt these new imaging possibilities to the biological material in use in research laboratories, to develop mathematical tools to study the huge amount of data generated and to translate these progresses into new software for medical image analysis and modelling.
The overall objectives of the project were:
1) Find the best incubation conditions to image developmental or diseases processes, and this led to new protocols that have now been published,
2) Find the best reporters to image populations of specific cell types or cells in a given physiopathological state, and this led to the development of new instrumental reporter transgenic lines, and new markers,
3) Find the best microscope setup to achieve the spatial and temporal resolution required to generate images amenable to high throughput analysis, and this led to the development of new imaging chambers and new microscopes that have been used through the network,
4) Develop new algorithms for automated and quantitative image analysis, and this led to widely available tools,
5) Develop new strategies for computational modelling and simulation of developmental and pathological processes that have been published.
Using the vertebrate embryos as models, the fellows were trained through research by addressing the following scientific bottlenecks and challenges:
• How to prepare and label the biological samples to image complex biological processes
• How to improve the existing microscopes
• How to deal with the huge amount of images generated during imaging sessions
• How to use the images to model the ongoing processes
• How to translate all this into new tools for medical image analysis
While it was very important for EU to train these future experts, in academia, and in companies to manage in vivo imaging, it was also important to train them to ethical issues and to all skills necessary for them to be good scientists involved in raising the scientific awareness of the general public. For this reason, the fellows have also been trained to become fully efficient scientists either in the academia or in the industry through network wide training events that included both technical training sessions and transferable skills training sessions.
The overall objectives of the project were:
1) Find the best incubation conditions to image developmental or diseases processes, and this led to new protocols that have now been published,
2) Find the best reporters to image populations of specific cell types or cells in a given physiopathological state, and this led to the development of new instrumental reporter transgenic lines, and new markers,
3) Find the best microscope setup to achieve the spatial and temporal resolution required to generate images amenable to high throughput analysis, and this led to the development of new imaging chambers and new microscopes that have been used through the network,
4) Develop new algorithms for automated and quantitative image analysis, and this led to widely available tools,
5) Develop new strategies for computational modelling and simulation of developmental and pathological processes that have been published.
Using the vertebrate embryos as models, the fellows were trained through research by addressing the following scientific bottlenecks and challenges:
• How to prepare and label the biological samples to image complex biological processes
• How to improve the existing microscopes
• How to deal with the huge amount of images generated during imaging sessions
• How to use the images to model the ongoing processes
• How to translate all this into new tools for medical image analysis
While it was very important for EU to train these future experts, in academia, and in companies to manage in vivo imaging, it was also important to train them to ethical issues and to all skills necessary for them to be good scientists involved in raising the scientific awareness of the general public. For this reason, the fellows have also been trained to become fully efficient scientists either in the academia or in the industry through network wide training events that included both technical training sessions and transferable skills training sessions.
ESRs have completed their “in house” training through research in their laboratories. They published scientific articles relating their results. Most relevant articles are co-authored by different beneficiaries of the ImageInLife network; this highlights the highly integrated work being performed.
The main achievements of ImageInLife are:
• The preparation of the biological samples for optimal imaging: 4 published scientific articles and 7 videos on the topic by consortium
• The staining strategies to highlight the relevant structures to be imaged: 2 scientific articles and 8 videos have been published on the topic by consortium
• Protocol for infections to study host-pathogen interactions: 2 published scientific articles and 3 videos on the topic
• New incubation chambers for in vivo imaging: 2 videos have been published on the topic
• New Light Sheet Fluorescence Microscopes to image biological processes down to the single molecule resolution: 9 videos on the topic
• Design of image processing and analysis methods: 11 published scientific articles and 6 videos
• New strategies to study Cell biomechanics: 5 published scientific articles and 4 videos
• New strategies to study Tissue geometry & physics: 4 published scientific articles and 2 videos
The main achievements of ImageInLife are:
• The preparation of the biological samples for optimal imaging: 4 published scientific articles and 7 videos on the topic by consortium
• The staining strategies to highlight the relevant structures to be imaged: 2 scientific articles and 8 videos have been published on the topic by consortium
• Protocol for infections to study host-pathogen interactions: 2 published scientific articles and 3 videos on the topic
• New incubation chambers for in vivo imaging: 2 videos have been published on the topic
• New Light Sheet Fluorescence Microscopes to image biological processes down to the single molecule resolution: 9 videos on the topic
• Design of image processing and analysis methods: 11 published scientific articles and 6 videos
• New strategies to study Cell biomechanics: 5 published scientific articles and 4 videos
• New strategies to study Tissue geometry & physics: 4 published scientific articles and 2 videos
We have succeeded in going beyond the state of the art as described in the initial project in the following orientations:
• New labels to image in vivo processes either during development or during infectious processes have been developed or implemented to study either mammalian or zebrafish early development. This has been the main topic of D1.3” In vivo tracers, reporters & actuators”, and partially that of D1.4 “New protocols to image the developing vertebrate embryos to the subcellular level”. The main progresses within ImageInLife have been related to innovative strategies to label specific cell populations or ongoing processes.
• New to tools to image biological processes in vivo, microscopes and incubation chambers have been developed by ESRs 10 and 14 and their respective beneficiary institutions. This has been the main topic of D2.1 “Incubation chambers”, D2.2 “Multimodal and multiscale LSFM workstation”, MS20 “Effective Super-Resolution imaging”, MS23 “VAST BioImager”, D2.3 “Super-resolution-LSFM for imaging of cellular processes within the embryo” and D2.4 “Image acquisition systems for infected embryos”. The development of new imaging chambers has been critical for the progress of the project, and together with new imaging strategies have yielded impressive results.
• New mathematical tools to analyse 3D or 4D image datasets have been the main topic of D3.1 “Design of image processing and analysis methods”, D3.2 “Computer implementation of image processing and analysis methods” and D3.3 “Application of image processing and analysis methods to ImageInLife data”
• New tools to model development and morphogenesis have been the main topic of D4.1 “Cell biomechanics”, D4.2 “Tissue geometry & physics”, and D4.5 “Search & optimisation”.
• New image processing solutions for high-content screenings using vertebrate embryos have been one of the main topic of D3.2 “Computer implementation of image processing and analysis methods”, and D3.3 “Application of image processing and analysis methods to ImageInLife data”.
• Implementation of these results in medical image processing software as it will bring the results of the network to the clinics for better diagnosis and choice of treatments. This has been the other main topic of D3.2 “Computer implementation of image processing and analysis methods”, and D3.3 “Application of image processing and analysis methods to ImageInLife data”.
The four last topics, at the heart of the transdisciplinary nature of ImageInLife, required close collaboration between wet biologists, mathematicians, physicists and computer scientists, have been very productive and critical to open the mind of the ESRs to the transdisciplinarity of their future research positions.
This transdisciplinarity of ImageInLife led to the production of both classical scientific articles published on line, and to the development of software packages publicly released on the ImageInLife community page on zenodo.org under open-source licences. They all have been developed with the contribution of at least one of the beneficiary private companies of ImageInLife, and we consider that this part of the project involving two very active private companies, Acquifer and TatraMed is a real success. These packages include the ImageInLib image processing library created by ESR13 in the frame of a collaboration between the ImageInLife teams from TatraMed Software s.r.o and Slovak University of Technology, and numerous tools developed by ESR12 from Acquifer for automatic object recognition on 4D images, stack projections, hyperstack manipulations, qualitative annotations and image classifications (see Milestone 28).
• New labels to image in vivo processes either during development or during infectious processes have been developed or implemented to study either mammalian or zebrafish early development. This has been the main topic of D1.3” In vivo tracers, reporters & actuators”, and partially that of D1.4 “New protocols to image the developing vertebrate embryos to the subcellular level”. The main progresses within ImageInLife have been related to innovative strategies to label specific cell populations or ongoing processes.
• New to tools to image biological processes in vivo, microscopes and incubation chambers have been developed by ESRs 10 and 14 and their respective beneficiary institutions. This has been the main topic of D2.1 “Incubation chambers”, D2.2 “Multimodal and multiscale LSFM workstation”, MS20 “Effective Super-Resolution imaging”, MS23 “VAST BioImager”, D2.3 “Super-resolution-LSFM for imaging of cellular processes within the embryo” and D2.4 “Image acquisition systems for infected embryos”. The development of new imaging chambers has been critical for the progress of the project, and together with new imaging strategies have yielded impressive results.
• New mathematical tools to analyse 3D or 4D image datasets have been the main topic of D3.1 “Design of image processing and analysis methods”, D3.2 “Computer implementation of image processing and analysis methods” and D3.3 “Application of image processing and analysis methods to ImageInLife data”
• New tools to model development and morphogenesis have been the main topic of D4.1 “Cell biomechanics”, D4.2 “Tissue geometry & physics”, and D4.5 “Search & optimisation”.
• New image processing solutions for high-content screenings using vertebrate embryos have been one of the main topic of D3.2 “Computer implementation of image processing and analysis methods”, and D3.3 “Application of image processing and analysis methods to ImageInLife data”.
• Implementation of these results in medical image processing software as it will bring the results of the network to the clinics for better diagnosis and choice of treatments. This has been the other main topic of D3.2 “Computer implementation of image processing and analysis methods”, and D3.3 “Application of image processing and analysis methods to ImageInLife data”.
The four last topics, at the heart of the transdisciplinary nature of ImageInLife, required close collaboration between wet biologists, mathematicians, physicists and computer scientists, have been very productive and critical to open the mind of the ESRs to the transdisciplinarity of their future research positions.
This transdisciplinarity of ImageInLife led to the production of both classical scientific articles published on line, and to the development of software packages publicly released on the ImageInLife community page on zenodo.org under open-source licences. They all have been developed with the contribution of at least one of the beneficiary private companies of ImageInLife, and we consider that this part of the project involving two very active private companies, Acquifer and TatraMed is a real success. These packages include the ImageInLib image processing library created by ESR13 in the frame of a collaboration between the ImageInLife teams from TatraMed Software s.r.o and Slovak University of Technology, and numerous tools developed by ESR12 from Acquifer for automatic object recognition on 4D images, stack projections, hyperstack manipulations, qualitative annotations and image classifications (see Milestone 28).