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This video shows how Convection-Enhanced Delivery (CED) works: the access port attached to the skull, the cannula aimed at target structure (red), infusion fills target structure (grey), and access port closed.3D animation created by John Doval (UCD)
Shortcomings of traditional drug delivery methods to the brainThe major challenge for delivering drugs to the brain is the blood-brain barrier, which acts as a tight membrane and surrounds the 400 miles of blood vessels within the brain. This barrier prevents most substances from passing into the brain from the bloodstream, including many drugs that could effectively treat neurological disorders. For this reason, traditional drug delivery methods such as swallowing a pill (oral) or receiving a shot (intravenous) fall short for neurological diseases. Drugs that do manage to cross the barrier must be administered at such high doses that they can lead to serious side effects. Systemic delivery can be toxic both to other parts of the body and other structures within the brain.
Our Solution: Local delivery of therapeutic agents with real-time image monitoringOur approach to this problem is to deliver therapeutic agents directly to a target structure within the brain. This gives high concentrations of the drug at the target without affecting either surrounding brain tissue or organs outside of the brain. To prevent unwanted leakage outside the target of interest we use magnetic resonance imaging (MRI) to track the distribution of infused drug. Proper use of real-time imaging prevents the infusion of drugs into incorrect regions or excess infusion of a drug. Over the past 10 years, we have optimized this procedure for clinical use.
Local Delivery SystemLocal delivery of therapeutic agents is accomplished by surgically inserting a cannula into a targeted brain structure. The therapeutic agents are administered in fluid form and can be distributed throughout this target with a procedure called convection-enhanced delivery (CED). CED uses a pressure gradient at the tip of the cannula to push interstitial fluid out of the way, enabling coverage of larger brain volumes than could be achieved by diffusion alone. Our research has shown that the rhythmic contraction of blood vessels also assists in this process.
Real-Time Image MonitoringWe use real-time magnetic resonance imaging (MRI) to achieve more complete coverage of the target structures. MRI is used at all stages of the procedure: to plan the cannula position, to map the target region and calculate the correct infusion volume, to guide the cannula to the target location and to track the fluid flow in real time. This enables us to target very small structures with high precision and to measure the exact distribution volume in the brain. We are now using this distribution data to develop predictive models for fluid distribution.
How it all works: step-by-step explanation
- The patient is given a baseline MRI for targeting purposes.
- Computer software calculates a trajectory for the cannula.
- A burr hole is surgically drilled into the skull to secure the aiming device.
- The aiming device is attached over the burr hole.
- The guidance system instructs the surgeon to align the aiming device to match the calculated trajectory.
- An MRI is taken before infusion begins to assure that the cannula is correctly placed.
- The cannula is inserted into the guidance system, and infusion begins at gradually increasing rates of flow. MRI are taken every 2 minutes to track drug distribution.
- When the infusion is finished, the cannula is removed and the incision is closed.