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A NeuroSpin team, in collaboration with researchers from SHFJ and MIRCen (CEA-Jacob), is identifying a predictive indicator of the potentially deleterious effect of devices using ultrasound to deliver drugs to the brain.
The brain is the best protected organ in our body thanks to various physical and biological barriers. Unfortunately, this property, which is normally beneficial, severely restricts access to brain tissue and thus the effectiveness of most known drugs.
It has been shown for 20 years that microbubbles circulating in the bloodstream can enter into oscillation under the effect of low intensity pulsed ultrasound and thus induce mechanical stress on the vascular walls. This is called cavitation. In response, the local permeability of the cerebral capillaries increases for a few hours, making possible the local delivery of therapeutic molecules injected at the same time. A NeuroSpin team is developing in preclinical studies - in collaboration with researchers from SHFJ and MIRCen - devices that work on this principle. The team is particularly interested in ways to adjust and monitor the acoustic power delivered, in order to guarantee the efficacy, reproducibility and safety of the protocols. In an article published in Scientific Reports, the researchers demonstrate the value of listening, at high frequency, to the signal returned by bubbles during ultrasound bursts in order to avoid their implosion, a potentially harmful phenomenon for tissues (causing hemorrhages, for example). How did they achieve this? By imploding, the bubbles go from a stable cavitation mode (purely harmonic emissions) to a so-called inertial mode (broadband emissions) that must be avoided. The researchers hypothesized the existence of a third intermediate mode (sub and ultra-harmonic emissions), which would be an early sign of bubble destabilization and the imminent appearance of deleterious inertial cavitation.
They highlighted this phenomenon in vivo and used it to define a new indicator calculated on the spectral signature of the signal reflected by the microbubbles, which is predictive of the appearance of the deleterious effects observed in MRI. A patent application has been filed by the CEA to protect this innovation.
The future use of this real-time indicator will make this promising medical technology safer.
Benoît Larrat (email@example.com)
A new safety index based on intrapulse monitoring of ultraharmonic cavitation during ultrasound-induced blood-brain barrier opening procedures. | Scientific Reports, 2020
A. Novell, H. A. S. Kamimura, A. Cafarelli, M. Gerstenmayer, J. Flament, J. Valette, P. Agou, A. Conti, E. Selingue, R. Aron Badin, P. Hantraye & B. Larrat
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.