Key Points
- Pre-operative perfusion MRI can help predict how microbubbles will distribute in the human brain.
- These findings pave the way for more personalized, image-guided planning of focused ultrasound during blood-brain barrier opening procedures.

A clinical study funded by the Foundation and led by neurosurgeon Francesco Prada, MD, and neuroradiologist Fabio Doniselli, MD, PhD, at Fondazione IRCCS Istituto Neurologico C. Besta in Milan, Italy, with participation from Frédéric Padilla, PhD, the director of the Foundation’s Gene and Cell Therapy Program, shows that pre-operative dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) can help predict how microbubbles will distribute in the human brain. This is a key step toward optimizing focused ultrasound modulation of blood-brain barrier permeability.
As part of the procedure for neurosurgical guidance during brain surgery, the Fondazione IRCCS C. Besta’s Institutional Review Board approved the intraoperative use of microbubbles to perform contrast-enhanced ultrasound (CEUS).
Building on the group’s earlier work (Scientific Reports, 2021), which showed that CEUS varied across brain structures and tumor types, this new study takes the next step. The team hypothesized that microbubble distribution could be inferred from MRI perfusion maps, since both reflect local blood flow. The objective of this study was to use perfusion MRI – specifically DSC – to predict microbubble distribution in human brain tissue.
To test this idea, the researchers compared preoperative DSC MRI data with intraoperative CEUS data, both obtained from 31 patients undergoing brain tumor surgery. Fusion imaging was employed for real-time neuronavigation during the surgical procedures, enabling precise alignment and guidance.
“It was surprising to observe the remarkable agreement between what is routinely described on our preoperative perfusion studies and the microbubble distribution obtained from intraoperative imaging,” said Dr. Doniselli. “These findings are facilitated by real-time fusion imaging and further support an even closer integration between pre-surgical neuroradiological assessment and intraoperative imaging.”
The results revealed that the MRI perfusion patterns correlated both qualitatively and quantitatively with intraoperative CEUS, suggesting that DSC MRI can serve as a noninvasive biomarker to predict microbubble distribution. Importantly, the CEUS images also allowed the team to quantitatively discriminate between tumoral and normal brain tissues.
These findings bridge MRI-derived perfusion patterns and real-time ultrasound observations, paving the way for more personalized, image-guided planning of microbubble-mediated focused ultrasound procedures to modulate the blood-brain barrier safely and precisely.
“This work could lead to new tools for planning blood-brain barrier opening procedures using pre-intervention MRI scans,” said Dr. Prada. “By anticipating where microbubbles will concentrate, clinicians can tailor focused ultrasound parameters to enhance delivery precision and safety.”
This project was partially led by Riccardo Ciocca, MD, while participating in the Foundation’s Global Internship Program. Dr. Prada also serves as a senior Brain Program Advisor at the Focused Ultrasound Foundation.
See NPJ Acoustics (Open Access)
Related Stories
Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging in Brain Structures June 2021