Columbia University's engineering researchers have developed a technique that utilizes extremely short pulses of ultrasound waves to open the blood-brain barrier (BBB), creating a host of possibilities for noninvasively treating brain disorders such as Alzheimer’s, Parkinson’s, atypical lobular hyperplasia (ALH) and epilepsy. The development opens a new pathway to reach neurons through the BBB because, until now, scientists have thought that long ultrasound pulses, which can inflict collateral damage, were required.
The study was published in the online early edition of the Proceedings of the National Academy of Sciences the week of Sept. 19.
“This is a great step forward,” said lead researcher Elisa E. Konofagou, PhD, associate professor of biomedical engineering and radiology, in a statement. “Devastating diseases such as Alzheimer’s and Parkinson’s that affect millions of people are currently severely undertreated. We hope our new research will open new avenues in helping eradicate them.”
The BBB prevents the entry of foreign molecules, protecting the brain from potentially toxic substances but also blocking the delivery of therapeutic drugs. Many patients with neurological disorders are therefore limited on treatment options.
The focused ultrasound treatment designed by Konofagou and her team can target the area of the hippocampus that is affected in early Alzheimer’s. In their study, they administered microbubbles to enhance the intended mechanical effect, and a high-field MRI to detect and map the area of the BBB opening and quantify its permeability.
“The premise behind our pulse-sequence design was to minimize damage by maintaining the lowest possible magnitude of cavitation activity still able to modify vascular permeability,” study authors wrote. “We aimed at simultaneously enhancing drug delivery distribution, dose and consistency by increasing the number of cavitation events and distributing them as homogeneously as possible.”
Researchers utilized the short ultrasound pulse to penetrate the BBB in mice, and to compensate for the reduced dose, they increased the frequency at which pulses were emitted. The possibility of microbubble destruction was compensated for by grouping pulses into bursts, according to the study.
Researchers intend to further study the development with therapeutic drugs. The BBB has been shown to recover within three hours to three days, and the researchers have also reported that transcranial human targeting of the hippocampus, caudate and putamen in the human brain is feasible in simulations and experiments.
"This previously undescribed basis may not only help enhance drug delivery in other organs beyond BBB disruption, but also improve safety by avoiding BBB disruption with other technologies such as diagnostic ultrasound imaging."