When digital technology enters the operating room to treat deep tumors

^{Illustration of the digital solution currently being used to evaluate the region to be treated using 3D Slicer plugins. (a): CBCT injected with the tumor (in white) and a blood vessel (in green) segmented by IR. (b): CBCT after needle insertion. The metal needles generate artifacts, and the regions of interest (ROIs) are no longer visible. (c): Non-rigid registration image (a) on image (b). (d) 3D visualization of the registered tumor and vessel, and identification of the needles by clicking on the image with the needles (b). (e): Selection of the electrical parameter of the ROIs and the voltage delivered. (f) Digital simulation showing the different amplitudes of the electric field (here 400 V/cm in yellow, 700 V/cm in red) on the image in order to see the coverage of the tumor by the electric field.}

Modeling to improve cancer therapy

The founding idea behind the AIMOKA project team (Advanced and Innovative Modeling for Percutaneous Ablation of Cancerous Tumors) arose from an observation: for certain deep, inoperable tumors, such as those of the liver or pancreas, percutaneous ablation by electroporation represents a promising avenue.

« These interventional radiology techniques involve inserting needles guided by medical imaging to apply an electric field and permeabilize cell membranes,” explains Clair Poignard, Inria research director and head of the project team. “The field applied is intense but brief, up to 2,000 volts per centimeter for a few hundred microseconds. » 

However, these percutaneous electroporation ablations face technical obstacles and a lack of standardized clinical criteria for evaluating their effectiveness, both during the procedure and during follow-up. This is precisely what the AIMOKA project team, created jointly by the Inria Center at the University of Rennes, Assistance Publique-Hôpitaux de Paris (AP-HP), and Sorbonne Paris-Nord University, wants to change. Its ambition is to develop a digital twin of percutaneous ablation to reduce recurrences and better understand therapeutic failures.

A collaboration between Inria and AP-HP

Mathematicians and clinicians are no strangers to collaborating on these topics. In 2020, the Bernoulli Lab was established at the Hôtel-Dieu hospital in Paris, providing a meeting place for Inria researchers and AP-HP doctors with the aim of accelerating research and innovation in digital health. It laid the groundwork for AIMOKA, well before its formalization in 2025. This laboratory initially hosted the NEPA and EVALHEP, research projects, which involved evaluating electroporation therapies.

Following a call for expressions of interest launched in 2024 by the Bernoulli Lab, the AIMOKA team took shape. It embodies the researchers' desire to go beyond simple one-off collaborations and develop a joint, long-term scientific project. “Without the Bernoulli Lab, we would not have become involved in AIMOKA” acknowledges Clair Poignard.

Real data from patients

In this partnership, AP-HP provides cutting-edge medical expertise and access to biomedical data in a hospital environment. Olivier Séror, university professor and hospital practitioner at GHU Paris Seine-Saint-Denis, co-founder of AIMOKA, emphasizes: “The data is real, coming from patients and procedures, with all the constraints of a hospital environment.”

The ongoing exchange between clinical reality and mathematical research thus makes it possible to integrate operational requirements from the design stage of digital solutions with a view to personalized medicine. “It is impossible, for example, to use supercomputers for simulation in operating rooms,” continues Olivier Séror. “We have to use less powerful machines that are compatible with the hospital environment. This constraint stimulates our innovation.”

The promise of percutaneous electroporation ablation

In this context, the AIMOKA team favors electroporation, a technique that involves applying an electric field to cell membranes, thereby increasing membrane permeability. Its effect can be irreversible when the energy delivered is so high that the membrane pores do not close, leading to cell death. With lower energies, it is reversible. A chemotherapeutic agent can then penetrate the cells, increasing its effectiveness without affecting the surrounding tissue.

“Prospective approaches are emerging, with the introduction of pieces of DNA (plasmids) through the membrane pores to modify the genetic program of the cells,” explains Oliver Sutter, interventional radiologist and third permanent member of AIMOKA. “We could perform ablation and stimulate the immune response simultaneously via electroporation to better fight the tumor. This research, which is still experimental, is part of the potential of immunotherapy in oncology.”

A digital twin to model percutaneous interventions

The deployment of these methods will be facilitated by accurate real-time mapping of electric fields. This is AIMOKA's central objective. “This digital twin of the procedure is a model of percutaneous ablation based on real data,” explains Clair Poignard. “It will reproduce the procedure as it actually takes place, taking into account the position of the needles placed by the radiologist. This innovative approach allows for dynamic optimization during the operation.”

So, when Olivier Séror places the electrodes, his colleague Olivier Sutter enters the coordinates of the needles into the operating room computer. A 3D map of the electric field is generated instantly. “We can see immediately whether the tumor is properly covered, and whether a needle needs to be moved or added,” continues the Inria researcher. “This intelligent planning could one day make it possible to robotize interventional radiology procedures,” imagines Olivier Séror.

Four priority areas of research 

In terms of prospects, the AIMOKA project team is focusing its work on four areas. The first, clinical, aims to define and standardize the necessary ablation margins according to the method (electroporation, radiofrequency, etc.), drawing on the expertise of the interventional radiology unit at Avicenne Hospital.

The second area, led by Olivier Sutter, focuses on the rapid assessment of therapeutic efficacy during the procedure using digital twins. The third area is fundamental research, led by Clair Poignard. It explores modeling at the cellular and tissue levels. "The benefit? Studying the biological response to anticipate therapeutic developments. The goal is to have a continuum from fundamental research to clinical practice in order to quickly integrate important advances into medical practice."

The final cross-cutting area is the development of digital tools for image visualization and registration (MRI, ultrasound, etc.), to enable back-and-forth exchanges between theory and clinical practice and to design an interface that can be used in healthcare.

« On all these topics, we are working with the MONC (Modeling in Oncology) team at the Inria Center at the University of Bordeaux, which contributes its expertise in image fusion and machine learning. In the future, we also plan to strengthen our ties with laboratories at Sorbonne Paris-Nord University, particularly LAGA (Laboratory for Analysis, Geometry, and Applications), which is particularly active in applied mathematics for biology and medicine » 

Research articles, patents, and startups in the process of being created

The AIMOKA project team already has several results to its credit. A study by Olivier Sutter, to be published in European Radiology, demonstrates the relevance of digital twins for the electroporation of liver tumors. “Based on cases treated at AP-HP and electric field mapping, we predicted which patients would respond to treatment and which were at risk of relapse,” he explains.

The joint work of MONC and AIMOKA has already resulted in a patent and a startup currently being created. “Our codes are mature enough to be used in clinical settings,” concludes Clair Poignard. “By bringing mathematics into the operating room, we want to accelerate the applicability of digital research in medicine.”