Research

Functional ultrasound imaging-guided acoustic vortex tweezers in thrombolysis

The aim of this project is to develop a functional sonography guided acoustic vortex tweezer (AVT) system to increase the local concentration of thrombolytic drugs for theranostic thrombolysis. The AVT will concentrate thrombolytic agents (tPA)-loaded microbubbles (tPA-MBs) within thrombosed vessels. In the meantime, the concentration and location of tPA-MBs can be monitored by plan wave ultrafast sonography imaging. Subsequently, these tPA-MBs can be triggered to release tPA drugs and to generate microstreaming at thrombosis area by low frequency ultrasound, improving the efficiency of thrombolysis. Since the AVT and tPA-MBs will generate shear waves in the thrombus during treatment, these shear waves can be used to generate elastic images of the thrombus for estimating the distribution of softness and hardness, thereby achieving real-time therapeutic purpose.

Suppression of epileptic seizures via piezoelectric MoS2 nanosheets-loaded microbubbles with focused ultrasound

To fill the unmet need of neuromodulation, this project proposes a strategy of loading MoS2 nanosheets (MoS2 NSs) microbubbles with focused ultrasound for neuromodulation. The MoS2 NSs were selectively released at targeted brain regions upon ultrasound sonication to achieve non-invasive, localized release and deep brain stimulation for neuromodulation. In the future, it can be applied to the treatment of other neurodegenerative diseases or as a new tool to explore neuroscience in the brain.

Microbubble UltraSound Directed Antidepressant Delivery

The therapeutic outcome of Intravenous route was also poor due to the blood-brain barrier hampered the extravasation of antidepressants into brain tissue. Focused ultrasound (FUS) with microbubbles (MBs) is a promising technique for noninvasive opening of the blood-brain barrier to allow delivery of therapeutics in the brain. Hence, this project is to develop a device which combining photoacoustic imaging navigation and FUS-MBs mediated drug delivery system to overcome the existing obstacles of major depression treatments. The antidepressants (Escitalopram) could immediately be transferred into disease area and could be traced by photoacoustic imaging.

Antiseizure drug-loaded nanodroplets with focused ultrasound for epilepsy therapy

Previous studies have proposed recondensation effect of acoustic nanodroplet vaporization, which undergoes some cycles of rapid vaporization followed by recondensation into liquid state, to locally release drugs, enhance ultrasound contrast imaging, and prevent brain tissue damage. The aim of this project is to fabricate the propofol-loaded nanodroplets (P-NDs) and estimate the drug loading, physical, and acoustic characteristics. To prevent brain tissue damage, the parameters of focused ultrasound would be regulated to accomplish the recondensation effect of P-NDs. A transcranial ultrasound imaging guided sonication system woud be established to real-time monitor the treatment location during epilepsy treatment.

Sonogenetic-induced dopaminergic neurons regeneration in Parkinson's Disease animal model

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder characterized by profound degeneration of mid-brain dopamine (DA) nigrostriatal neurons linked to serious dementia and motor symptoms. Several groups have validated that optogenetics and deep brain stimulation techniques could promote the regeneration of injured neurons. However, these are invasive treatment, requiring implantation of optic fiber or electrodes into brain tissue may cause tissue damage. The aim of this project is to propose a non-invasive sonogenetic strategy to transcranial activate the regeneration of dopaminergic neurons, relieving PD symptoms. The experiment processes included two stages: (1) designing an ultrasound sensing DNA (Prestin plasmid) loaded microbubbles, and transfecting Prestin plasmid onto the dopaminergic neurons of PD’s mice with ultrasound; (2) repetitive activating the transfected dopaminergic neurons by ultrasound, promoting the release of neurotrophic factors for repairing the injured neurons. Future works included to apply this technique to treat other neurodegenerative disorders, or as a new tool for exploring brain neuroscience.

Improving tumor microenvironment through oxygen-loaded microbubbles trapping by acoustic vortex tweezer

This project proposes to improve tumor oxygenation by oxygen-loaded microbubbles (O2-MBs) for regulating tumor microenvironment. The intratumoral oxygen release by ultrasound-stimulated O2-MBs destruction could inhibit tumor hypoxia and angiogenesis to induce vascular normalization. Since abnormal tumor vasculature would restrict the transport of O2-MBs, we develop a novel acoustic vortex tweezer system to elevate the concentration of O2-MBs within tumors without increasing the doses of O2-MBs. By applying the phase dislocation on the array transducer, the acoustic vortex tweezer propagates with a tornado structure to trap and collect O2-MBs in the center of acoustic field (potential-well). Moreover, our project integrates acoustic vortex tweezer with ultrafast ultrasonic plane-wave imaging to provide a real-time monitor system for O2-MBs treatment. After trapping O2-MBs by acoustic vortex tweezer, a cascading O2-MBs destruction pulse would be used to locally release oxygen in tumors. The feasibility of tumor microenvironment regulations including vascular normalization, immune activation, and metastasis would be evaluated after enhancing tumor oxygenation. This project designs a systemic platform which integrates acoustic vortex tweezer and ultrafast imaging to trap, monitor, and destruct O2-MBs for regulating tumor microenvironments.