Objective/Rationale:
Current drug therapy for Parkinson’s disease has limited long term effectiveness. To improve therapy in the future, delivery of therapeutic agents to the brain will be an increasingly important means of treating PD. Current neurosurgical procedures are essentially blind, leading to errors in targeting desired brain structures and in delivery. For emerging therapeutics, such as gene and stem cell therapies, targeting precision and delivery confirmation are of paramount importance. This project seeks to provide the means to visually confirm targeting and delivery of therapeutics during surgery in real time.
Project Description:
We propose to improve the delivery of therapeutics to the brain by obtaining real time visual confirmation of targeting, delivery and spread of delivered therapeutic agents using optical coherence tomography (OCT) imaging. OCT is a real-time optical imaging system that produces high-resolution images of the brain. It is particularly well suited to application in the brain because of its ability to differentiate and identify brain regions as well as blood vessels at a resolution of about 20 nm. OCT allows visualization of injected volumes as small as 0.2 microliters and their spread through surrounding tissue. We will analyze the effects on delivery and distribution of a variety of parameters such as the delivery needle size, infusion rate, infusion volume, and region targeted.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Current surgical techniques can lead to mistargeting or poor delivery resulting in treatment that is too focal (dyskinesias) or nonspecific. The ability to accurately identify targets deep in the brain will open up new potential treatment for movement-related and other symptoms of PD. The impact of developing OCT for neurosurgery extends well beyond simply monitoring injected material. Its targeting capability makes it a platform technology not only for therapeutic delivery but also for placement of drug infusion catheters and deep brain stimulating electrodes.
Anticipated Outcome:
The most important outcome will be to provide a system that gives real time intraoperative feedback on location in the brain and success of delivery of therapeutic agents. We hope to learn how injected materials of different sizes move through brain tissue, particularly in areas targeted for treatment of PD.
Progress Report
Catheter-based optical coherence tomography (OCT) provides a means of imaging structures deep within the brain in real time. It also allows visualization of delivered substances during delivery. The research team has integrated the OCT probe with a delivery system that allows the delivery of viral vectors to targets in the brain. To date, the group has optimized the delivery parameters for the system and will be comparing spread of the delivered viral vector expression with real-time images of the spread of the delivery taken during the procedure.