CE19 - Technologies pour la santé

3D integrated multifunctional MRI sensors based on Molded Interconnect Device technology in tissue engineering regenerative medicine – ESTIMATE

3D integrated multifunctional MRI sensors based on Molded Interconnect Device technology in tissue engineering regenerative medicine

In the last decades, the progress in the field of tissue engineering for regenerative medicine (TERM) has been tremendous. However, there is still no effective 3D method to evaluate non-invasively in vitro and in vivo engineered tissues. Therefore, the main objective of ESTIMATE is to democratize multiparametric MRI for the characterization of engineered tissues from the synthesis to the implantation stage.

Developing a new family of multifunctional “MRI probes” easy to handle, and able to acquire in vitro and in vivo high quality images of small biological samples

Among the imaging methods, MRI is one of the best imaging modalities for studying soft tissues. However, the use of preclinical MRI in the community of tissue engineering is not available as it remains a very complex technology for a non-expert user. This is particularly true for imaging very small leaving samples that requires cutting-edge technology not routinely available on preclinical MR-platform. Therefore, the main objective of ESTIMATE is to democratize multiparametric MRI for the characterization of engineered tissues from the synthesis to the implantation stage. This will be achieved by developing a new family of multifunctional “MRI probes” easy to handle, and able to acquire in vitro and in vivo high quality images of small samples. To this end, Molded Interconnect Device (MID) technology will be used that allows, thanks to the third dimension, combining more functionalities, reducing the number of components, and facilitating complex assemblies. The challenge of this project lies in the compact combination of MR-signal detection devices, monitoring devices, using materials compatible with living tissues and MRI environment constraints.

The ultimate goal of ESTIMATE is to design and manufacture multifunctional MRI probe for TERM evaluation in vitro and in vivo. This goal will be preceded by a series of new advances:
-Design simulation and fabrication of the first 3D RF coil for MRI using MID technology
-Design and fabrication of a MRI probe combining a RF coil with the monitoring devices needed for either in vitro, or in vivo study using MID technology
-Design and fabrication of a MRI probe combining a RF coil with monitoring devices, a piezoelectric transducer for MRE and a cryogenic fluidic system to cool down the RF coil.
-Test of the 3D multifunctional probe on an imaging platform dedicated to preclinical studies with routine exams, to verify the simplicity of use of this probe and validate the development.
-Characterization over time of 3D-printed skin in vitro and after implantation on mice.

Today there is no turnkey preclinical MRI technology to accurately evaluate over time the quality of engineered tissues. Different solutions have been tested but, most of the time, remain in the hands of experts. The benefit of preclinical MRI for the field of tissue engineering is held in check. ESTIMATE will overcome this limitation by combining and improving key technological solutions to perform easy and high quality preclinical MRI, which so far have never been combined, thus facilitating imaging of engineered tissue constructs. Manufacturing with MID will help pushing the limits of manufacturing MRI set up. This technology opens the perspective to manufacture optimal RF coils geometry determined by simulation that to date was not manufacturable. Moreover, these probes could be easily duplicated with very good reproducibility at reasonable costs. Finally, the compacity of the MRI probe will increase the available space in volume coils by reducing the thickness of the probe and by embedding all monitoring and sensor devices. Today in a standard MR-bore of 90 mm, the biggest internal diameter of a RF coil is 72 mm, which represents a 36% lost in volume. And this lost is only due to the occupation of the RF coil without the peripherals.

ESTIMATE will help to design new biomaterials well-characterized (structure, composition and function) over time for regenerative medicine. Imaging of tissues will be used as a feedback. This will allow for adjustments to be made throughout the manufacturing process to improve quality of tissues and hence to speed up the translation of tissue engineered products to the clinic. Finally, the cost-effectiveness of this technology will allow its use in all preclinical MRI centers and why not the distribution of the devices worldwide. In France, the probe distribution could be initiated by the national infrastructure “France Life Imaging” which “coordinates nation-wide research activities concerned with in vivo imaging” and “provide scientists a convenient access to a complete range of imaging technologies (150 imaging systems) and integrated services”.

1. 3D Plastronics for Smartly Integrated Magnetic Resonance Imaging Coils. Submitted in Frontiers in Physics and Medical Imaging
2. Lombard, P.; Gerges, T.; Allard, B.; Lambert, S. A.; Cabrera, M. Plastronique 3D et 3D-MID, programme innovant d’enseignement supérieur et de formation à l’Université de Lyon. J3eA 2019, 18, 1014. doi.org/10.1051/j3ea/20191014.
3. Piezoelectric actuators for MRE Submitted in Frontiers to the following topic research: Innovative Developments in Multi-Modality Elastography
4. Design of a volume MRI coil by metalyzing 3D printing substrates by electroless and/or electroplating processes. ISMRM 2019 Oral presentation1. 5. Séminaire GRED Clermont Ferrand 31 Mars 2019

In the last decades, the progress in the field of tissue engineering for regenerative medicine (TERM) has been tremendous. Nowadays, even if vascularizing tissues is still challenging, it becomes possible to coax stem cells to differentiate into lineage-specific cells or to create fine-tuned biomaterials matching to target tissue properties. Moreover, three-dimensional (3D) printing technologies are now able to create a tissue with specific shape and size requirements. However, there is still no effective 3D method to evaluate non-invasively in vitro and in vivo engineered tissues. It is now more vital than ever to make the fabrication process as reproducible as possible in order to optimize it for tissue implantation. Moreover, we have to evaluate the changes over time of the tissues. Furthermore, tissue functions have to be well quantified. Thus, the development of innovative imaging methods for 3D volume assessment of tissue engineered constructs at different scale (space and time) has become inescapable.
Among the imaging methods, MRI is one of the best imaging modalities for studying soft tissues. However, the use of preclinical MRI in the community of tissue engineering is not available as it remains a very complex technology for a non-expert user. This is particularly true for imaging very small leaving samples that requires cutting-edge technology not routinely available on preclinical MR-platform.
Therefore, the main objective of ESTIMATE is to democratize multiparametric MRI for the characterization of engineered tissues from the synthesis to the implantation stage. This will be achieved by developing a new family of multifunctional “MRI probes” easy to handle, and able to acquire in vitro and in vivo high quality images of small samples. To this end, Molded Interconnect Device (MID) technology will be used that allows, thanks to the third dimension, combining more functionalities, reducing the number of components, and facilitating complex assemblies.
The challenge of this project lies in the compact combination of MR-signal detection devices, monitoring devices, using materials compatible with living tissues and MRI environment constraints.
The ultimate goal of ESTIMATE is to demonstrate the advantages brought by the MID technology to design and manufacture multifunctional MRI probe for TERM evaluation in vitro and in vivo. The developed technology has the potential to improve and to optimize the fabrication process which could lead to a breakthrough in regenerative medicine.
This objective is thoroughly structured in three main tasks: RF coil design and characterization, implementation of peripherals and in vitro/in vivo evaluation of engineered tissues. At the end of the project, the manufactured 3D multifunctional probe will be duplicated and tested on imaging platforms dedicated to preclinical studies with routine exams. Thus, it will be possible to verify the simplicity of use of this probe and validate the development.
The integration of cutting edge strategies for signal detection, combined with additional functions, to design an MRI probe answers a critical need for tissue engineering community. Another important potential impact of this project is that it is a new tool for the validation of imaging biomarkers.

Project coordination

Simon Lambert (Laboratoire Ampère)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

AMPERE Laboratoire Ampère

Help of the ANR 303,706 euros
Beginning and duration of the scientific project: - 48 Months

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