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English
Context
The heart is a complex organ that performs the essential function of circulating blood in the human body. This function is essential to life and heart disease remains an extremely important cause of death in industrialized countries.
The development of diagnostic tools or therapeutic methods requires a detailed understanding of the physiology of the heart: movement / deformation of the muscle, hemodynamics in the various cavities, electrical activation etc... Moreover, as the heart is made up of muscle fibers, it also seems very relevant to try to imagine as precisely as possible the local fibrous structure of the tissue in order to establish a link between this local structure and the cardiac function and more generally with the development of various pathologies. Similarly, the vascularization of the cardiac muscle and its imbrication with the fibrous structure are as much knowledge that could justify a future clinical criterion in cardiovascular disease. At the international level, a single team has already succeeded in proposing imaging of cardiac muscle anisotropy [1].
Objectives
The objective of this thesis is to develop and validate an imaging method dedicated to the 3D quantification of the tissue and vascular structure of the heart muscle. For this purpose, three elementary steps will have to be solved: 1) measurement of cardiac muscle anisotropy, 2) measurement of micro-vascularization in 3D ultrasound imaging, and 3) in vitro/in vivo validation of the proposed approach.
Methodology
This project is part of the continuation of a thesis funded by LabEx PRIMES, which proposed a first acquisition and processing pipeline to measure the local anisotropy of different media in vitro and in vivo, but without succeeding in applying it to a real ex vivo peace of cardiac muscle. Methodological developments are still needed to optimally realize and access the exact 3D orientation of the local anisotropy. Moreover, in the perspective of in vivo cardiac imaging, increasing the field of view is a mandatory step.
For the measurement of vascularization, it seems relevant to start from standard Doppler techniques. However, the transition to 3D and the size of the vessels to be imaged will require specific methodological work to evaluate accurately the cardiac vascularization [2, 3]. Specific approaches, via optimized wall filters, will be crucial to measure the flow in these vessels. The validation of this new imaging mode will be carried out on micro-fluidic systems.
Finally, the complete validation of the imaging and measurement pipeline will be performed on pig hearts during a specific open-heart operation protocol. Indeed, access to the heart will be simplified and pathologies may be induced on the heart in order to evaluate the change in anisotropy and/or loss of vascularization.
Maturity
The field of ultrasound is currently undergoing a real revolution. After 2D ultrafast imaging, which is beginning to become a standard in research laboratories, 3D ultrafast imaging is in the process of emerging. Thanks to the pooling of ultrasound equipment from two Lyon laboratories (CREATIS-LabTau), it is possible to produce 3D ultrasound volumes at high rates (several hundred volumes per second), which will be crucial for visualizing/measuring micro-vascularization. The continuation of innovative work and research in the field of high frame rate 3D ultrasound imaging is therefore crucial for the international recognition of the ultrasound community at the University of Lyon [4].
The previous thesis, which began with various works on the measurement of anisotropy, has lifted a number of barriers and allows us to envisage in an extremely positive way the continuation of this innovative research theme.
In order to consider the transfer of these 3D imaging methodologies to the clinic, an adaptation of the strategies initially developed on a 1024-element 3D probe will be proposed with the objective of reducing the number of elements to 256 (multiplexed 3D probe) and using a single imaging system.
International collaboration
The thesis will be carried out in collaboration with the University of Florence in Italy where the candidate will be supervised by Professor Piero Tortoli. From a thematic point of view, the skills of the Florence team are complementary to ours since their work concerns the development of imaging systems for the study of flow while we work more on imaging methods. Thus, the joint developments structure / flow will be facilitated and will find an immediate impact. From an experimental point of view, the equipment of the French and Italian laboratories is also complementary. Indeed, the Florence laboratory is equipped with a sparse spiral probe for 3D imaging and their mastery of the imaging system opens the way to real-time imaging of tissue structure. Finally, this collaboration that we have maintained for many years will allow the student to complete his thesis in the framework of co-supervision agreement.
How to apply
Send a CV, a cover letter and the obtains grades in M1&M2 to:
francois.varray@creatis.insa-lyon.fr
The selected candidate will be presented to the MEDA doctoral school in order to obtain the grant.
References
[1] C. Papadacci et al, "Imaging the dynamics of cardiac fiber orientation in vivo using 3D Ultrasound Backscatter Tensor Imaging," Rep. Sci, vol. 7, no. 1, p. 830, Apr. 2017.
[2] S. Harput et al. 3-D Super-Resolution Ultrasound (SR-US) Imaging using a 2-D Sparse Array with High Volumetric Imaging Rate.
[3] M. Correia et al., “Quantitative imaging of coronary flows using 3D ultrafast Doppler coronary angiography,” Phys. Med. Biol., vol. 65, no. 10, p. 105013, Jun. 2020.
[4] L. Petrusca et al, "Fast Volumetric Ultrasound B-Mode and Doppler Imaging with a New High-Channels Density Platform for Advanced 4D Cardiac Imaging/Therapy," Appl. Sci. vol. 8, no. 2, p. 200, Feb. 2018.