Transcranial Focused Ultrasound Research Articles

Transcranial focused ultrasound to the thalamus alters anesthesia time in rats

A pulsed application of focused ultrasound (FUS) to the regional brain tissue alters the state of tissue excitability and thus provides the means for noninvasive functional neuromodulation. We report that the application of transcranial FUS to the thalamus of anesthetized rats reduced the time to emergence of voluntary movement from intraperitoneal ketamine/xylazine anesthesia. Low-intensity FUS was applied to the thalamus of anesthetized animals. The times required for the animals to show distinct physiological/behavioral changes were measured and compared with those times required in a control session without sonication. The sonication significantly reduced the time to show pinch response and voluntary movement. The modulatory effects of FUS on anesthesia suggest potential therapeutic applications for disorders of consciousness such as minimally consciousness states.

Micro-SPECT/CT–Based Pharmacokinetic Analysis of 99mTc-Diethylenetriaminepentaacetic Acid in Rats with Blood–Brain Barrier Disruption Induced by Focused Ultrasound

This study evaluated the pharmacokinetics of (99m)Tc-diethylenetriamine pentaacetate acid ((99m)Tc-DTPA) after intravenous administration in healthy and F98 glioma-bearing F344 rats in the presence of blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). The pharmacokinetics of the healthy and tumor-containing brains after BBB-D were compared to identify the optimal time period for combined treatment. Healthy and F98 glioma-bearing rats were injected intravenously with Evans blue (EB) and (99m)Tc-DTPA; these treatments took place with or without BBB-D induced by transcranial FUS of 1 hemisphere of the brain. The permeability of the BBB was quantified by EB extravasation. Twelve rats were scanned for 2 h to estimate uptake of (99m)Tc radioactivity with respect to time for the pharmacokinetic analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to examine tissue damage. The accumulations of EB and (99m)Tc-DTPA in normal brains or brains with a tumor were significantly elevated after the intravenous injection when BBB-D was induced. The disruption-to-nondisruption ratio of the brains and the tumor-to-ipsilateral brain ratio of the tumors in terms of radioactivity reached a peak at 45 and 60 min, respectively. EB injection followed by sonication showed that there was an increase of about 2-fold in the tumor-to-ipsilateral brain EB ratio of the target tumors (7.36), compared with the control tumors (3.73). TUNEL staining showed no significant differences between the sonicated tumors and control tumors. This study demonstrates that (99m)Tc-DTPA micro-SPECT/CT can be used for the pharmacokinetic analysis of BBB-D induced by FUS. This method should be able to provide important information that will help with establishing an optimal treatment protocol for drug administration after FUS-induced BBB-D in clinical brain disease therapy.

A PVDF Receiver for Ultrasound Monitoring of Transcranial Focused Ultrasound Therapy

Focused ultrasound (FUS) shows great promise for use in the area of transcranial therapy. Currently dependent on MRI for monitoring, transcranial FUS would benefit from a real-time technique to monitor acoustic emissions during therapy. A polyvinylidene fluoride receiver with an active area of 17.8 mm (2) and a film thickness of 110 mum was constructed. A compact preamplifier was designed to fit within the receiver to improve the receiver SNR and allow the long transmission line needed to remove the receiver electronics outside of the MRI room. The receiver was compared with a 0.5 mm commercial needle hydrophone and focused and unfocused piezoceramics. The receiver was found to have a higher sensitivity than the needle hydrophone, a more wideband response than the piezoceramic, and sufficient threshold for detection of microbubble emissions. Sonication of microbubbles directly and through a fragment of human skull demonstrated the ability of the receiver to detect harmonic bubble emissions, and showed potential for use in a larger scale array. Monitoring of disruption of the blood-brain barrier in rats showed functionality in vivo and the ability to detect subharmonic, harmonic, and wideband emissions during therapy. The receiver shows potential for monitoring acoustic emissions during treatments and providing additional parameters to assist treatment planning. Future work will focus on developing a multi-element array for transcranial treatment monitoring.

Quantitative evaluation of the use of microbubbles with transcranial focused ultrasound on blood–brain-barrier disruption

It has been shown that focused ultrasound (FUS) can disrupt the blood–brain barrier (BBB) noninvasively and reversibly at target locations when applied in the presence of ultrasound contrast agent (UCA). In this study, the dose-dependent effects of UCA on BBB disruption were investigated in the brains of 16 male Wistar rats sonicated by 1.0-MHz transcranial FUS, with the UCA present at four doses. The BBB disruption was evaluated quantitatively based on the extravasation of Evans blue (EB). The amount of EB extravasation in the brain increased with the quantity of UCA injected into the femoral vein prior to sonication. Moreover, the use of a suitable dose of UCA resulted in the BBB disruption being concentrated in the focal region instead of the entire brain. Our results indicate that injecting an appropriate quantity of UCA effectively increases and localizes the BBB disruption induced by transcranial FUS sonications.