# Optimization of ultrasound-mediated drug delivery to the brain under clinically relevant conditions

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $511,748

## Abstract

Summary
The blood-brain barrier prevents most drugs from reaching the central nervous system and is one of the biggest
problems in developing new effective therapies for patients with brain tumors, neurodegenerative diseases, and
other disorders. The use of ultrasound in combination with injected microbubble agents has emerged as a prom-
ising method to temporarily disrupt the barrier. After over a decade of preclinical studies in animals, multiple
commercial systems have been developed and clinical trials have begun. Early experience with these trials have
shown several problems that were predicted by the preclinical work. The clinical treatments use lower doses of
microbubbles, have to overcome the variable attenuation of the human skull, and are often in white matter. As a
result, treatments have been suboptimal. The purpose of this proposal is to provide a roadmap to clinical success
for ultrasound-mediated blood-brain barrier opening. We will develop new treatment planning methods that ac-
count for the human skull, electronic steering of the focused ultrasound beam, and variations in microbubble
concentrations in different tissue structures. These methods will be employed to improve safety and control of
the procedure. Next, we will investigate whether we can improve our ability to control the procedure in white
matter targets and evaluate the safety of repeated blood-brain barrier disruption in white matter targets. Finally,
using what we have learned, we will investigate whether we can deliver sufficient drugs to treat a highly infiltrating
tumor model. If successful, this work could have a significant impact on future use of this exciting technology.

## Key facts

- **NIH application ID:** 10499767
- **Project number:** 1R01EB033307-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Nathan J. McDannold
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $511,748
- **Award type:** 1
- **Project period:** 2022-09-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499767

## Citation

> US National Institutes of Health, RePORTER application 10499767, Optimization of ultrasound-mediated drug delivery to the brain under clinically relevant conditions (1R01EB033307-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10499767. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*