Canadian researchers, lead by Montreal doctor Gilles Soulez, have devised a unique method for treating liver cancers using magnet-guided microrobots in an MRI equipment. The concept of introducing microscopic robots into the circulation to cure the human body is not novel. It is also not science fiction.
Miniature biocompatible robots constructed of magnetizable iron oxide nanoparticles, guided by an external magnetic field, have the potential to perform highly targeted medical treatments. Until recently, there has been a technological stumbling block: the gravitational force of these microrobots outweighs the magnetic force, limiting their guiding when the tumor is higher than the injection site.
While the magnetic field of the MRI is strong, the magnetic gradients required for navigation and generating MRI images are weak.
“To solve this problem, we developed an algorithm that determines the position that the patient’s body should be in for a clinical MRI to take advantage of gravity and combine it with the magnetic navigation force,” said Dr. Gilles Soulez, a researcher at the CHUM Research Centre and the director of the radiology, radio-oncology, and nuclear medicine departments at Université de Montréal.
“This combination action makes it easier for the microrobots to move to the artery branches which feed the tumour,” he explained. “By varying the direction of the magnetic field, we can accurately guide them to sites to be treated and thus preserve the healthy cells.”
Our magnetic resonance navigation approach can be done using an implantable catheter like those used in chemotherapy. The other advantage is that the tumours are better visualized on MRI than on X-rays.
Dr. Gilles Soulez
Toward greater precision
Published in Science Robotics, this proof of concept could change the interventional radiology approaches used to treat liver cancers. The most common of these, hepatocellular carcinoma, is responsible for 700,000 deaths per year worldwide, and is currently most often treated with transarterial chemoembolization.
Requiring highly qualified personnel, this invasive treatment involves administering chemotherapy directly into the artery feeding the liver tumour and blocking the blood supply to the tumour using microcatheters guided by X-ray.
“Our magnetic resonance navigation approach can be done using an implantable catheter like those used in chemotherapy,” said Soulez. “The other advantage is that the tumours are better visualized on MRI than on X-rays.”
For this study, Soulez and his research team collaborated with those of Sylvain Martel (Polytechnique Montreal) and Urs O. Häfeli’s (University of British Columbia). The study’s first author, Ning Li, is a postdoctoral fellow in Dr. Soulez’s laboratory.
The scientists were able to create “particle trains,” aggregates of magnetizable microrobots, after developing an MRI-compatible microrobot injector. These have a stronger magnetic force, making them easier to steer and identify on the MRI device’s images.
This allows the scientists to confirm not only that the train is moving in the right direction, but also that the treatment dose is appropriate. Over time, each microrobot will carry a fraction of the treatment to be provided, therefore radiologists must understand how many there are.
A good sense of direction
“We carried out trials on twelve pigs in order to replicate, as closely as possible, the patient’s anatomical conditions,” said Soulez. “This proved conclusive: the microrobots preferentially navigated the branches of the hepatic artery which were targeted by the algorithm and reached their destination.”
His team made sure that the location of the tumour in different parts of the liver did not influence the effectiveness of such an approach.
“Using an anatomical atlas of human livers, we were able to simulate the piloting of microrobots on 19 patients treated with transarterial chemoembolization,” he said. “They had a total of thirty tumours in different locations in their livers. In more than 95 per cent of cases, the location of the tumour was compatible with the navigation algorithm to reach the targeted tumour.”
Despite scientific advancements, clinical implementation of this technology remains a long way off.
“First of all, using artificial intelligence, we need to optimize real-time navigation of the microrobots by detecting their location in the liver and also the occurrence of blockages in the hepatic artery branches feeding the tumour,” he stated.
Scientists will also need to predict blood flow, patient location, and magnetic field direction using software that replicates fluid flow via channels. This will allow us to examine the impact of these characteristics on the transit of microrobots to the target tumour, improving the accuracy of the method.
