A5006234149- Ultrasound and Hyperthermia Applications
- Photoacoustic and Ultrasonic Imaging
- Ultrasound and Cavitation Phenomena
- Ultrasound Imaging and Elastography
- Advanced MRI Techniques and Applications
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- Neonatal and fetal brain pathology
- Flow Measurement and Analysis
- Asthma and respiratory diseases
- Dermatology and Skin Diseases
- Advanced Neuroimaging Techniques and Applications
- Ultrasound in Clinical Applications
- Plant Virus Research Studies
- Vagus Nerve Stimulation Research
- IL-33, ST2, and ILC Pathways
- Traumatic Brain Injury and Neurovascular Disturbances
Columbia University
2013-2023
Jackson Laboratory
2023
University of California, San Diego
2023
Boston Children's Hospital
2020-2022
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2022
National Taiwan University
2009
Abstract Brain diseases including neurological disorders and tumors remain under treated due to the challenge access brain, blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is sole method open BBB noninvasively, locally, transiently facilitate delivery, while translation clinic challenging long procedure, targeting limitations, or invasiveness current systems. In order...
Focused ultrasound (FUS) has been shown promise in treating the brain locally and noninvasively. Transcranial passive cavitation detection (PCD) provides methodology for monitoring treatment real time, but skull effects remain a major challenge its translation to clinic. In this study, we investigated sensitivity, reliability, limitations of PCD through primate (macaque human) skulls vitro. The results were further correlated with vivo macaque studies including transcranial calibration...
The delivery of drugs to specific neural targets faces two fundamental problems: (1) most do not cross the blood-brain barrier, and (2) those that do, spread entire brain. To date, there exists only one non-invasive methodology with potential solve these selective barrier (BBB) opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB in non-human primate does require simultaneous MRI...
Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool assess control treatment. While it demonstrated a strong correlation in small animals, its translation primates remains question due anatomically different highly heterogeneous structures gray white matteras well dense vasculature. In addition, drug...
Gene editing in the brain has been challenging because of restricted transport imposed by blood–brain barrier (BBB). Current approaches mainly rely on local injection to bypass BBB. However, such administration is highly invasive and not amenable treating certain delicate regions brain. We demonstrate a safe effective gene technique using focused ultrasound (FUS) transiently open BBB for intravenously delivered CRISPR/Cas9 machinery
Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into brain. Intranasal (IN) administration is a promising approach for drug delivery brain, bypassing BBB; however, its application has been restricted particularly potent substances and it does not offer localized specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver at targeted locations. The present study...
Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization potentially improved in vivo stability, payload, and minimal interference outside of the focal zone compared microbubbles. While feasibility blood-brain barrier (BBB) opening using has been previously reported, characterization associated not achieved. It was hypothesized that outcome droplet's sensitivity to acoustic energy, can be modulated boiling point liquid core. Therefore, this study,...
Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated as a vector for targeted drug delivery treatment central nervous system diseases. These were labeled fluorophore 5-dodecanoylaminfluorescein. mouse brains vivo presence these trans-blood-brain new approach, compared previously studies group, where...
To fully assess contrast-enhanced acoustic bioeffects in diagnostic and therapeutic procedures, the mechanical properties of microbubbles need to be considered. In present study, direct measurements microbubble stiffness were performed using atomic force microscopy by applying nanoscale compressions (up 25 nN/s) on size-isolated, lipidcoated (diameter ranges 4 6 μm 8 μm). The was found lie between 22 mN/m decrease exponentially with size within diameter range investigated. No cantilever...
Passive acoustic mapping enables the spatiotemporal monitoring of cavitation with circulating microbubbles during focused ultrasound (FUS)-mediated blood-brain barrier opening. However, computational load for processing large data sets maps or more complex algorithms limit visualization in real-time treatment and adjustment. In this study, we implemented a graphical unit (GPU)-accelerated sparse matrix-based beamforming time exposure acoustics neuronavigation-guided system cavitation. The...
Lipid-shelled microbubbles have been used in ultrasound-mediated drug delivery. The physicochemical properties of the microbubble shell could affect delivery efficiency since they determine mechanical properties, circulation persistence, and dissolution behavior during cavitation. Therefore, aim this study was to investigate effects on brain via blood-brain barrier (BBB) opening vivo using monodisperse with different phospholipid components. monolayer were varied by phospholipids hydrophobic...
Microbubble (MB)-assisted focused ultrasound is a promising technique for delivering drugs to the brain by noninvasively and transiently opening blood-brain barrier (BBB), monitoring BBB using passive cavitation detection (PCD) critical in detecting its occurrence, extent as well assessing mechanism. One of main obstacles achieving those objectives large animals transcranial attenuation. To study effects, response through in-vitro non-human primate (NHP) skull was investigated. In-house...
In order to fully assess contrast-enhanced acoustic bioeffects in diagnostic and therapeutic applications, the mechanical properties of microbubbles need be taken into account. current study, direct measurements microbubble apparent stiffness were performed using atomic force microscopy by applying nanoscale compressions (up 25 nN/s) on size-isolated, phospholipid-coated (diameters between 4-6 6-8 μm). The was found lie 4 22 mN/m decrease exponentially with size within diameter range...
Doppler ultrasound for quantifying blood and tissue motion is angle-dependent has maximum detectable velocity limitation. Speckle tracking, on the other hand, can be utilized to estimate vectors. The combination of high frame-rate imaging speckle tracking potential achieve accurate estimation but computation requirement may a concern. It purpose this study assess performance data acquisition called tracking. Main factors under investigation include image signal-to-noise ratio (SNR)...
Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization potentially improved in vivo stability, payload, and minimal interference outside of the focal zone compared microbubbles. While feasibility blood-brain barrier (BBB) opening using has been previously reported, characterization associated not achieved. It was hypothesized that outcome droplet sensitivity to acoustic energy, can be modulated boiling point liquid core. Therefore, this study,...
FUS in conjunction with systemically administered microbubbles has been previously shown to open the Blood-Brain Barrier (BBB) locally, non-invasively and reversibly non-human primates. However, a trans-BBB pharmacodynamic analysis not performed as of yet. The objective this study was perform such an analysis, i.e. permeability, relaxivity gadolinium concentration mapping, NHP brain vivo order further investigate effect FUS, its dependence on acoustic parameters used for safe efficient...
The delivery of drugs to specific neural targets faces two fundamental problems: Most do not cross the blood-brain barrier and those that spread all parts brain. To date there exists only one non-invasive methodology with potential solve these selective disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in non-human primate. Using this system is technically no more challenging than...
A passive cavitation detector (PCD) has previously been developed and used to transcranially acquire the acoustic emissions stemming from interaction between microbubble brain tissue during FITS-induced bloodbrain barrier (BBB) opening, thereby determining pressure threshold of inertial (IC) based on quantification broadband response, i.e. dose (ICD). Given that at certain pressures BBB opens as a result stable only, (SCD) is introduced quantified opening in mice non-human primates using...
Focused ultrasound (FUS) with microbubbles (MB) is promising for assisting the delivery of drugs across blood-brain barrier (BBB). To assess safety and efficacy, monitoring using passive cavitation detection (PCD) critical yet reliability transcranial in large animals remained questioned. study primate skull effect, PCD through in-vitro monkey human skulls vivo monkeys during sonication (FUS frequency: 500 kHz) were investigated, use in-house made lipid-shelled, monodisperse MB (median...
The delivery of drugs to specific neural targets faces two fundamental problems: most do not cross the blood-brain barrier and those that spread all parts brain. To date there exists only one non-invasive methodology with potential solve these selective disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in nonhuman primate. Here, we tested accuracy system by targeting caudate nucleus...
Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase permeability blood-brain barrier (BBB), thus allowing targeted delivery therapeutic agents brain for treatment central nervous system diseases. Currently, are only that have used facilitate FUS-induced BBB opening. However, they constrained within intravascular space due their micron-size diameters, limiting effect at or near microvessels. In...