SBIR Phase I: Transcranial Dynamic Focused Ultrasound for the Non-Invasive Opening of the Blood-Brain Barrier (BBB)

This SBIR Phase I project aims to develop technology designed to provide physicians with a new capability to manage patients with brain diseases such as brain cancers, Alzheimer’s or Parkinson’s. One reason brain disease is difficult to treat is the existence of the blood-brain barrier (BBB) that prevents almost all therapeutic agents from reaching diseased tissue from blood. The proposed technology enables opening the BBB in a non-invasive manner with a system that is portable and may be deployed in an out-patient or a clinic setting. This system could impact the cost burden of managing patients with brain diseases and provide better quality of life. The proposed project develops methods to accurately direct focused beams of ultrasound to therapy targets within the patient’s brain from an array of ultrasound transducers embedded in a cap-like device conformed comfortably to a patient’s head. In the last several years, focused ultrasound with microbubbles (an FDA approved ultrasound contrast agent) has been used to transiently open the BBB to administer drugs or provide therapy. The proposed cap-like device includes mechanisms both to conform to the patient head and to measure the resulting alignment to the patient anatomy. The envisioned method is to acquire information on cap placement and MR and CT images of the specific patient in advance so that the therapeutic ultrasound can then be directed accurately to targets within the patient's brain. The proposed work includes a) developing beamforming algorithms applicable to a range of patient head sizes, with transducer elements arranged on the conforming cap; and (b) understanding and mitigating potential sources of errors limiting the performance. The project will conduct simulation and analysis using MR and CT images from real patients, obtained from the U.S. National Library of Medicine Visible Human Project, resulting in specifications suitable for construction of a laboratory device for verification and validation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.