- The Foundation’s Research Awards Program initiated nine preclinical studies from October through December 2022, the fourth quarter of last year.
- The funded projects address brain, bone, low back pain, and breast cancer applications of focused ultrasound.
The Foundation’s Research Awards Program initiated nine new preclinical studies from October through December 2022, the fourth quarter of last year. The funded projects address brain, bone, low back pain, and breast cancer applications of focused ultrasound.
“All of the preclinical brain projects are linked to an initiative that came out of the May 2021 glioblastoma workshop,” said Lauren Powlovich, MD, the Foundation’s Associate Chief Medical Officer. “The aim of this group of projects is to identify a method to better quantify the amount of drug delivered to brain tissue after blood-brain barrier opening (BBBO). We are meeting quarterly to discuss progress and new ideas.”
Each newly initiated project is listed below.
Probing the Abilities of Contrast-Enhanced MRI to Track Microbubble-Enhanced Focused Ultrasound Nano-Medicine Delivery in the Brain and Brain Tumors led by Costas Arvanitis, PhD, at the Georgia Institute of Technology
For this project, researchers will determine how to confirm therapeutic delivery of nanoparticles to the brain during microbubble-enhanced focused ultrasound (MB-FUS) procedures. The goal is to improve the delivery of therapeutic nanoparticles to brain tumors by studying optimal nanoparticle properties and methods to confirm nanoparticle delivery in the brain and brain tumors.
Mapping Drug Concentrations After Blood-Brain Barrier Disruption Using MALDI Mass Spectrometry Imaging led by Nathan McDannold, PhD, at Brigham and Women’s Hospital
For this project, researchers will explore the use of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to quantify the amount of therapeutic delivered to brain tissue after BBBO, then creating specific calibration curves to compare with the MRI images. The goal is to identify a method to better quantify the amount of drug delivered to the brain tissue following BBBO.
PET-Labeling and Testing of Paclitaxel Nanoformulations with Microbubbles and Focused Ultrasound led by Graeme Woodworth, MD, at the University of Maryland School of Medicine
For this project, researchers will determine whether PET-labeling of nanoparticle therapeutics could enable quantitative visualization of localized nanoparticle delivery during microbubble-enhanced blood-brain barrier opening with clinical focused ultrasound systems in advanced preclinical models of glioblastoma.
Mapping of Antibody and Liposome Permeability into the Brain Following Focused Ultrasound Treatment Through T1/T2w Dynamic Contrast-Enhanced (DCE) Magnetic Resonance Imaging led by Antonios Pouliopoulos, PhD, at King’s College Hospital in London
For this project, the research team will confirm focused ultrasound–mediated delivery of antibody- and liposome-based therapies by delivering two MR-labelled model drugs across the blood-brain barrier (BBB) and then conducting DCE MRI scans to determine the extent of drug delivery within the tissue.
Evaluation of MRI Visualization of Focused Ultrasound–Induced Blood-Brain Barrier (BBB) Opening in White Matter led by Meghan O’Reilly, PhD, at Sunnybrook Health Sciences Centre
For this project, researchers will determine how to improve drug delivery to white matter in the brain. Contrast-enhanced MRI is used to assess changes in BBB permeability following focused ultrasound treatment but the contrast enhancement in white matter is lower than in grey matter, so research is needed to be able to use MRI visualization for both applications.
MRI Compatible Optical-Driven Focus Ultrasound for Neuromodulation led by Chen Yang, PhD, at Boston University
Ultrasound neural modulation is an emerging noninvasive neuromodulation tool. The goal of this project is to develop a compact, MRI-compatible, optically driven focused ultrasound source for ultrasound neural modulation with a broader accessibility than standard focused ultrasound systems. Its application in noninvasive brain modulation and its efficacy in treating epilepsy in a mouse model will be demonstrated.
Ultrasound-Triggered Gelation to Treat Discogenic Lower Back Pain led by Constantin Coussios, PhD, at the University of Oxford
This one-year collaborative study will combine the materials engineering expertise at Imperial College with the biomedical ultrasound expertise at the University of Oxford to optimize material formulations and focused ultrasound exposure parameters with the objective of translating these techniques for percutaneous nucleus pulposus replacement. Doing so would offer a new minimally invasive day case procedure to treat discogenic lower back pain and restore spinal function.
Patterning of Mesenchymal Stem Cell Differentiation for Bone Regeneration Using Focused Ultrasound–Mediated Hydrogel Stiffening led by Mario Fabiilli, PhD, at the University of Michigan
For this project, researchers will use focused ultrasound to alter the stiffness of a custom acoustic responsive scaffold (ARS) and stimulate bone regeneration. The ARS contains mesenchymal stem cells encapsulated within hydrogels The hydrogel acts as a surrogate for the native extracellular matrix. The studies seek to demonstrate a proof-of-concept for implanting ARS at the site of bone loss.
Preclinical High-Intensity Focused Ultrasound (HIFU) Treatment of Breast Adenocarcinoma Using a Noninvasive Toroidal Transducer led by David Melodelima, PhD, at Inserm LabTAU
For this project, researchers will determine whether HIFU ablation of breast adenocarcinoma is feasible and effective with a toroidal transducer. The group will use a clinical device that has previously been effective for liver metastases and pancreatic tumors.