A team from the Higher Council for Scientific Research (CSIC), the Polytechnic University of Valencia (UPV) and Columbia University (USA), has created and tested 3D-printed acoustic holograms in an animal model to improve the treatment of diseases such as Alzheimer's or Parkinson's, among others. His work has been on the cover of the journal 'IEEE Transactions on Biomedical Engineering'.
The holograms devised by the team of researchers from the CSIC and the UPV allow the blood-brain barrier to be opened "selectively, efficiently and in a very focused way", facilitating the administration of therapeutic drugs for the treatment of pathologies that affect the central nervous system, as reported by the CSIC.
The researcher at the Institute of Instrumentation for Molecular Imaging (I3M), a joint center of the CSIC and the UPV, Francisco Camarena, has detailed that focused ultrasound has "great potential for the treatment of neurological diseases, thanks to its ability to generate therapeutic effects accurately and non-invasively.
"However, applying them to the structures of the central nervous system is complicated due to two major drawbacks: the effects of aberration and attenuation of the skull bones and the complex and extensive spatial distribution of the deep structures of the brain", Camarena pointed out.
The acoustic holograms devised by the UPV and CSIC researchers allow a "more controlled" opening of the blood-brain barrier than that achieved using ultrasound exclusively "and, what is more important, they can correct those aberrations introduced by the cranium". At the same time, they can generate a multifocal ultrasound beam on "specially relevant" brain structures.
«Thanks to our holograms, the ultrasound beam is focused and adapted bilaterally and very precisely on parts of the brain of great therapeutic interest, such as, for example, on the two nuclei that make up the hippocampus, related to Alzheimer's disease, and that it has a capricious three-dimensional shape”, added Noé Jiménez, Juan de la Cierva researcher at the UPV.
This is the first time that the opening of the blood-brain barrier has been achieved simultaneously in both hemispheres. In addition, the team from the CSIC, the UPV and Columbia University has achieved it with a much higher resolution than the standard, which allows "a better localization of the area to be treated, minimizing the volume of healthy brain tissue that would be sonified and at the same time reducing the cost and time of intervention».
The ultrasound emitter is like a "loudspeaker" that vibrates at half a million oscillations per second. The hologram is placed in front of him and is pierced by the wave; at the same time, a cone filled with water is placed in contact with the skull, through which the wave propagates before reaching the patient; Next, the wave crosses the skull, finally focusing on the brain area of therapeutic interest.
On the other hand, microbubbles (contrast agents) are introduced into the bloodstream which, when they reach the capillaries of the brain and coincide with the ultrasound, begin to vibrate. The epithelial tissue of the blood-brain barrier begins to give way and that is when “small cracks” open through which the drug molecules pass for the treatment of the pathology that affects the central nervous system.
The hologram is printed, personalized for each case, with a 3D printer. “For example: Let's say the doctor needs to sonify a patient's tonsil. To do this, he would provide us with a CT scan and an MRI of the patient, on which he would identify and segment the treatment area. Based on this information, we design the hologram we need to achieve the sonification of the region of interest", explained Sergio Jiménez, doctor from the UPV and currently hired by the Columbia group, who also highlights the low cost of holograms, which would range between forty and 300 euros depending on the medical application.
Currently, the team of researchers from the UPV, the CSIC and Columbia University is working on verifying this new technology for opening the blood-brain barrier in macaques, and is designing the first protocols for experimentation in humans, to the treatment of brain tumors and to carry out brain neurostimulation studies.