Research

Mission statement

 

We develop innovative focused ultrasound (FUS) techniques to diagnose and treat brain diseases and understand brain functions. Our team is currently working on developing FUS techniques for brain drug delivery, brain biomarker release for liquid biopsies, and brain stimulation. 

Project 1: FUS-enabled drug delivery to the pons for the treatment of diffuse intrinsic pontine glioma (DIPG)

Pediatric brain tumors kill more children than any other cancers, including leukemia. Among all pediatric brain tumors, DIPG, a high-grade glioma that arises in the pons, is the most common brainstem tumor of childhood and the single greatest cause of brain tumor-related death in children. We integrated focused ultrasound, radiolabeled nanoclusters, and positron emission tomography (PET) imaging and achieved noninvasive and localized nanoparticle delivery to the pons with concurrent in vivo quantitative imaging to evaluate delivery efficiency. Our long-term goal is to apply this drug delivery platform to the treatment of DIPG.

PET images of radiolabeled nanoparticles delivered to the FUS-targeted pons in the mouse brain

Project 2: FUS combined with microbubble-mediated intranasal delivery (FUSIN)

The intranasal (IN) route can deliver therapeutic agents directly from the nose to the brain, bypassing the BBB and minimizing systemic exposure. FUSIN can enhance the accumulation of IN-administered agents at the FUS-targeted brain location. We hypothesize that the potential mechanism of FUSIN is the “microbubble pumping effect”: microbubble oscillations push and pull on the blood vessel, which leads to expansion and contraction of the vessel and surrounding tissue.

 

Project 3: FUS-enabled brain tumor blood-based liquid biopsy (FUS-LBx)

For brain tumor liquid biopsy, one major challenge is the hindrance of tumor biomarker release into the bloodstream by the BBB. We hypothesize that FUS-mediated BBB disruption opens “two-way trafficking” between brain and blood. While circulating molecules can be allowed to enter the brain using FUS-mediated BBB disruption, brain biomarkers (e.g., tumor markers) can also be released into the blood circulation for liquid biopsies. We were the first to introduce the FUS-LBx technique for noninvasive diagnosis of brain diseases.

Revised based on https://directorsblog.nih.gov/2018/01/30/new-liquid-biopsy-shows-early-promise-in-detecting-cancer/

Project 4: Functional optical imaging feedback-controlled cellular-level ultrasound stimulation (FOCUS)

Although neurotechnologies are rapidly advancing, we lack noninvasive neuromodulation tools with high spatiotemporal precision, which would radically change neuroscience research and enable clinically noninvasive brain stimulation with high spatiotemporal precision. The objective of this study is to develop a noninvasive, cell-type specific, imaging feedback-controlled neuromodulation tool that we call FOCUS.

 

We appreciate the support of the following agencies.