Dataset Information

Use of transcranial low-intensity focused ultrasound for targeted delivery of stem cell-derived exosomes to the brain.

ABSTRACT: The blood-brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.

SUBMITTER: Haroon J

PROVIDER: S-EPMC10584845 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Use of transcranial low-intensity focused ultrasound for targeted delivery of stem cell-derived exosomes to the brain.

Haroon J J Aboody K K Flores L L McDonald M M Mahdavi K K Zielinski M M Jordan K K Rindner E E Surya J J Venkatraman V V Go-Stevens V V Ngai G G Lara J J Hyde C C Schafer S S Schafer M M Bystritsky A A Nardi I I Kuhn T T Ross D D Jordan S S

Scientific reports 20231018 1

The blood-brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ult ...[more]

PMID: 37853206

Similar Datasets

Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has gained considerable attention as a promising noninvasive neuromodulatory technique for human brains. However, the complex morphology of the skull hinders scholars from precisely predicting the acoustic energy transmitted and the region of the brain impacted during the sonication. This is due to the fact that different ultrasound frequencies and skull morphology variations greatly affect wave propagation through the skull.PurposeAlthough the acoustic properties of human skull have been studied for tFUS applications, such as tumor ablation using a multielement phased array, there is no consensus about how to choose a single-element focused ultrasound (FUS) transducer with a suitable frequency for neuromodulation. There are interests in exploring the magnitude and dimension of tFUS beam through human parietal bone for modulating specific brain lobes. Herein, we aim to investigate the wave propagation of tFUS on human skulls to understand and address the concerns above.MethodsBoth experimental measurements and numerical modeling were conducted to investigate the transmission efficiency and beam pattern of tFUS on five human skulls (C3 and C4 regions) using single-element FUS transducers with six different frequencies (150-1500 kHz). The degassed skull was placed in a water tank, and a calibrated hydrophone was utilized to measure acoustic pressure past it. The cranial computed tomography scan data of each skull were obtained to derive a high-resolution acoustic model (grid point spacing: 0.25 mm) in simulations. Meanwhile, we modified the power-law exponent of acoustic attenuation coefficient to validate numerical modeling and enabled it to be served as a prediction tool, based on the experimental measurements.ResultsThe transmission efficiency and -6 dB beamwidth were evaluated and compared for various frequencies. An exponential decrease in transmission efficiency and a logarithmic decrease of -6 dB beamwidth with an increase in ultrasound frequency were observed. It is found that a >750 kHz ultrasound leads to a relatively lower tFUS transmission efficiency (<5%), whereas a <350 kHz ultrasound contributes to a relatively broader beamwidth (>5 mm). Based on these observations, we further analyzed the dependence of tFUS wave propagation on FUS transducer aperture size.ConclusionsWe successfully studied tFUS wave propagation through human skulls at different frequencies experimentally and numerically. The findings have important implications to predict tFUS wave propagation for ultrasound neuromodulation in clinical applications, and guide researchers to develop advanced ultrasound transducers as neural interfaces.

Dataset Information

Use of transcranial low-intensity focused ultrasound for targeted delivery of stem cell-derived exosomes to the brain.

Publications

Use of transcranial low-intensity focused ultrasound for targeted delivery of stem cell-derived exosomes to the brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets