Our mission is to develop innovative focused ultrasound (FUS) techniques for improving the lives of patients with brain diseases. Our team is currently working on developing the following FUS techniques: 1) Sonodelivery: brain drug delivery techniques for the treatment of brain cancer, 2) Sonobiopsy: brain tumor biomarker release techniques for the diagnosis of brain cancer, 3) Sonogenetics: brain stimulation techniques for understanding brain functions, 4) Ultrasound-induced artificial hibernation, and 5) Sonoclearance: brain waste clearance techniques for the treatment of neurodegenerative diseases.
For a brief introduction to our research, please see the following talk presented by Dr. Chen at the Inauguration Symposium of WashU chancellor, Andrew Martin.
Project 1: Sonodelivery – 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 2: Sonobiopsy – FUS-enabled brain tumor blood-based liquid biopsy
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 sonobiopsy technique for noninvasive diagnosis of brain diseases.
Project 3: Sonogenetics – Ultrasound combines with genetics for noninvasive cell-type selective neuromodulation
Although neurotechnology is 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.
Project 4: Artificial hibernation – Ultrasound neuromodulation evokes hibernation/torpor-like state
Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. We report noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). Our findings establish ultrasound as a promising technology for the noninvasive and safe induction of a torpor-like state. Link to video introduction
Project 5: Sonoclearance – Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles
The glymphatic system is a waste clearance system in the brain analogous to the lymphatic system in peripheral organs. Glymphatic system impairment might contribute to brain disease pathologies, including those in neurodegenerative diseases, traumatic brain injury, and stroke. We revealed that ultrasound could mechanically enhance glymphatic transport. Ultrasound can be utilized as a noninvasive and nonpharmacological approach to mitigate brain diseases caused by impaired glymphatic function. Link to video introduction