Guiding and monitoring focused ultrasound mediated blood–brain barrier opening in rats using power Doppler imaging and passive acoustic mapping

Abstract

The blood–brain barrier (BBB) prevents harmful toxins from entering brain but can also inhibit therapeutic molecules designed to treat neurodegenerative diseases. Focused ultrasound (FUS) combined with microbubbles can enhance permeability of BBB and is often performed under MRI guidance. We present an all-ultrasound system capable of targeting desired regions to open BBB with millimeter-scale accuracy in two dimensions based on Doppler images. We registered imaging coordinates to FUS coordinates with target registration error of 0.6 ± 0.3 mm and used the system to target microbubbles flowing in cellulose tube in two in vitro scenarios (agarose-embedded and through a rat skull), while receiving echoes on imaging transducer. We created passive acoustic maps from received echoes and found error between intended location in imaging plane and location of pixel with maximum intensity after passive acoustic maps reconstruction to be within 2 mm in 5/6 cases. We validated ultrasound-guided procedure in three in vivo rat brains by delivering MRI contrast agent to cortical regions of rat brains after BBB opening. Landmark-based registration of vascular maps created with MRI and Doppler ultrasound revealed BBB opening inside the intended focus with targeting accuracy within 1.5 mm. Combined use of power Doppler imaging with passive acoustic mapping demonstrates an ultrasound-based solution to guide focused ultrasound with high precision in rodents.

Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array

“…We matched estimated in vivo microbubble concentrations by converting the microbubble dose (20 µl/kg) and the average blood volume in adult macaques (60 ml/kg) which gives a ratio of 20 µl microbubble solution per 60 ml of water to use in the flow phantom (Bender 1955). For water tank measurements we used in-house manufactured microbubbles following a previously described method (Singh et al 2022). Stirring was required to keep the bubble solution mixed during experiments and was achieved by placing a reservoir on a magnetic stirrer.…”

Nanomaterials as drug delivery agents for overcoming the blood-brain barrier: A comprehensive review

“…It is possible that FUS will produce better liposomes that deliver medications., such as cisplatin or doxorubicin, to increase BBB permeability and decrease tumour growth in mice. FUS enhances the relative permeability of the BBB in a time-dependent manner: an experimental study" by Yufeng Zhou et al [ 125 ]. Rat glioma tumours can be targeted with paclitaxel-carrying liposomes that can pass through the BBB.…”

Decoding Motor Plans Using a Closed-Loop Ultrasonic Brain-Machine Interface

“…As demonstrated here, fUS neuroimaging captures neurovascular changes on the order of a second and is also stable over more than 1 month. Combined with neuromodulation techniques such as focused ultrasound, it may be possible to not only record from these distributed corticolimbic populations but also precisely modulate specific mesoscopic populations 39,40 .…”