Rapid short-pulses of focused ultrasound and microbubbles deliver a range of agent sizes to the brain.

Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood-brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains.

Successful synthesis of a glial-specific blood-brain barrier shuttle peptide following a fragment condensation approach on a solid-phase resin.

Successful manual synthesis of the TD2.2 peptide acting as a blood-brain barrier shuttle was achieved. TD2.

Inhibition of the angiotensin II type 2 receptor ATR is a novel therapeutic strategy for glioblastoma.

Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (ATR) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through ATR. We repurposed EMA401, an ATR antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of ATR-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity.

Liposome delivery to the brain with rapid short-pulses of focused ultrasound and microbubbles.

Liposomes are clinically used drug carriers designed to improve the delivery of drugs to specific tissues while minimising systemic distribution. However, liposomes are unable to cross the blood-brain barrier (BBB) and enter the brain, mostly due to their large size (ca. 100 nm).

Modulation of amyloid-β aggregation by metal complexes with a dual binding mode and their delivery across the blood-brain barrier using focused ultrasound.

One of the key hallmarks of Alzheimer's disease is the aggregation of the amyloid-β peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt amyloid-β aggregation. While a handful of molecules have been shown to inhibit amyloid-β aggregation , there remains a lack of data reported due to their inability to cross the blood-brain barrier.

Imaging With Therapeutic Acoustic Wavelets-Short Pulses Enable Acoustic Localization When Time of Arrival is Combined With Delay and Sum.

Passive acoustic mapping (PAM) is an algorithm that reconstructs the location of acoustic sources using an array of receivers. This technique can monitor therapeutic ultrasound procedures to confirm the spatial distribution and amount of microbubble activity induced. Current PAM algorithms have an excellent lateral resolution but have a poor axial resolution, making it difficult to distinguish acoustic sources within the ultrasound beams.

Doppler Passive Acoustic Mapping.

In therapeutic ultrasound using microbubbles, it is essential to drive the microbubbles into the correct type of activity and the correct location to produce the desired biological response. Although passive acoustic mapping (PAM) is capable of locating where microbubble activities are generated, it is well known that microbubbles rapidly move within the ultrasound beam. We propose a technique that can image microbubble movement by estimating their velocities within the focal volume.

Neuron labeling with rhodamine-conjugated Gd-based MRI contrast agents delivered to the brain via focused ultrasound.

Gadolinium-based magnetic resonance imaging contrast agents can provide information regarding neuronal function, provided that these agents can cross the neuronal cell membrane. Such contrast agents are normally restricted to extracellular domains, however, by attaching cationic fluorescent dyes, they can be made cell-permeable and allow for both optical and magnetic resonance detection. To reach neurons, these agents also need to cross the blood-brain barrier.

Rapid Short-pulse Ultrasound Delivers Drugs Uniformly across the Murine Blood-Brain Barrier with Negligible Disruption.

Background Previous work has demonstrated that drugs can be delivered across the blood-brain barrier by exposing circulating microbubbles to a sequence of long ultrasound pulses. Although this sequence has successfully delivered drugs to the brain, concerns remain regarding potentially harmful effects from disrupting the brain vasculature. Purpose To determine whether a low-energy, rapid, short-pulse ultrasound sequence can efficiently and safely deliver drugs to the murine brain.

Targeted Delivery of DNA-Au Nanoparticles across the Blood-Brain Barrier Using Focused Ultrasound.

Nanoparticles have been widely studied as versatile platforms for in vivo imaging and therapy. However, their use to image and/or treat the brain is limited, as they are often unable to cross the blood-brain barrier (BBB). To overcome this problem, herein we report the use of focused ultrasound in vivo to successfully deliver DNA-coated gold nanoparticles to specific locations in the brains of mice.