From the heart to the brain
Nejib Zemzemi has been an Inria researcher in the CARMEN project team since 2012. During his first years at the Inria Bordeaux - Sud-Ouest centre, his research focused on the electrical activity of the heart and inverse problems in electrocardiography. “These problems try to explain the source of cardiac arrhythmias based on measurements,” the researcher explains. To understand the full dynamics of the heart and how it functions, he also investigated digital tools for developing simulators of cardiac activity. To achieve this, he worked with the Liryc University Hospital Institute (IHU), like many other members of the CARMEN team.
At the same time, Emmanuel Cuny a University Professor and Hospital Practitioner at Bordeaux University Hospital, was researching how to improve the daily life of patients suffering from tremors, using deep brain stimulation. One of the biggest challenges in his research was finding the right “geographic” location to place the electrodes in the brain. The main technique for accessing the area concerned - which is difficult to get to even when it is known - involves a major and rather traumatic operation for the patient who is awake for most of the procedure, since the aim is to observe their responses to the different stimulations in order to find the exact location in which to implant the electrodes.
How can this technique be improved? This was Emmanuel’s question. Is it possible to use preoperative data to define with millimetre precision where the electrodes should be implanted? In applied mathematics, this is called an “inverse problem”.
After discussing the issue with IHU cardiologists, he was put in touch with the CARMEN project team which was known for its research in applied mathematics in medicine and inverse problems in particular. That was back in 2015: the journey had begun.
From research to transfer
Research to solve the problem began with work on “learning methods”. Nejib Zemzemi, who was experienced in using this method in cardiology, tested the approach with the brain. The idea was to supply enough data to an algorithm to allow it to learn and propose efficient results when questioned with a new dataset.
The team’s main advantage was the quantity of data available for “training the model”. Using information from patients already treated with electrodes, particularly pre-and post-operative imaging, the algorithm was able to reliably help surgeons. The digital tool could accurately determine where to implant the stimulation device in the brain for each new patient. The predictions made by the prototype proved correct.
In 2018, the researchers decided to develop a program that could be used in clinical situations
My aim was to enable the fruit of our work to be used by neurosurgeons, says Nejib Zemzemi
The program, initially called OptimDBS, allows neurosurgeons to make specific marks on the patient’s MRI to predict where to implant the stimulator. The MRI is then transferred to a “planning station” and the operation can begin using a surgical robot. To develop the program, the scientists were supported by Inria through in-house schemes for supporting technology transfer and development. Initially, the team planned to transfer their work to an industrial company and filed a patent application for their research with the help of the technology transfer acceleration company Aquitaine Science Transfert (SATT aquitaine).
Besides the patent application, SATT Aquitaine very quickly identified possibilities for technology transfer. Our aim was to transfer our research, while still continuing to work on the scientific subject, , explains Nejib
SATT Aquitaine has invested €226,000 since April 2020 to help mature the technical and clinical proof of concept of the project and finance patent protection. Inria, for its part, has invested 100,000 euros in 2018 to produce a version that can be used in a clinical setting and has registered the OptimDBS software and its evolutions, which are essential to guarantee the technology's long-term future.
Creating a deeptech start-up
Among other possible avenues for transfer, the team responded to a ‘University Hospital Research” call for proposals via the French National Research Agency, which provides the opportunity for academic and industrial structures to work together to develop technology and ultimately to transfer them to industry. Unfortunately, their application was unsuccessful. However, while preparing their response to the call for proposals, the researchers learned more about the question of transfer, so much so that they decided to embark on the adventure themselves! “We had no training in business creation: we’re researchers, our aim is to further research. I had never wanted to become an entrepreneur,” says Nejib Zemzemi.
After searching in vain for a co-founder with a business and marketing profile, Emmanuel and Nejib decided to “go it alone”. Alone? Not really! They received help and support from SATT Aquitaine and took training proposed by SATT Aquitaine and Inria Startup Studio (ISS). With the arrival of the health crisis, the course they had begun through the ISS at Lyon School of Management had to be cancelled. At the same time, the HEC Paris business school launched a competition called “HEC Challenge Plus”, which the researchers won, earning them training in business creation.
We have to admit that the PACTE law, which was passed just as were thinking about creating a start-up, facilitated our decision to become entrepreneurs, says Nejib.
The law PACTE
The next step: part-time entrepreneurs
After its creation, ReBrain signed a license agreement to exploit the program developed together.
"Our start-up should allow us to market the program while continuing our research. Thanks to the PACTE law, as of July this year, I will be dividing my time between Inria and ReBrain.
Although the software is already currently used for research, one of our challenges is to complete the process of getting it certified as a “medical device” so that it can be used as a clinical tool”. European and international requirements for this type of material are fairly strict but the team has recruited an engineer who is specialised in the question of regulations and, together, they have a good chance of completing the process and submitting their certification application by 26 May this year.