Significance: Accurate targeting, guidance and monitoring of interventional therapy in the brain are critical for maximizing the effectiveness and safety during and following neurosurgical procedures. Magnetic resonance imaging (MRI) is a critical tool for planning and guiding neurosurgical procedures. In most cases, the MRI is obtained during a pre-operative session;however, either brain shift, errors in device guidance or device malfunction can lead to poor outcomes. In particular for infusion-based therapies, the location of the infusion cannula in the brain, the distribution of the therapeutic agent, and loss of the therapeutic agent through backflow or other mechanisms may significantly influence the therapeutic outcome. While luminaries have shown how intraoperative MRI can visualize infusion distribution qualitatively, neurosurgeons will largely resist MRI's complicated workflow, lack of interactive feel, and inability to interface with the surgical workstations they commonly utilize to exploit imaging. Hypothesis: We hypothesize that by decoupling imaging control from MR scanner manufacturers, we can produce an encapsulated, real-time MRI platform technology, in this case designed for guiding and monitoring drug infusions. The customizable platform, ultimately designed and controlled by our device and surgical workstation partners, will reduce the time of MR-guided targeting, quantitatively visualize the current infusion in real-time, and provide an intuitive, interactive workflow familiar to surgeons. Preliminary Data: We have developed a prototype platform for real-time, interactive navigation of cannulas into the brain and the imaging technology to quantitatively measure infusion distribution. We have successfully applied the platform to guide 30 convection enhanced delivery procedures in in-vivo swine brains and one gene delivery in a NHP model.
Specific Aims : This project includes further development and evaluation of the platform for navigation and monitoring of neuroinfusion procedures.
In Specific Aim 1, we will simplify and accelerate the interface platform for guiding and monitoring infusion procedures. We will integrate new imaging tools into the platform for obtaining the roadmap image for targeting and imaging sequences for monitoring the infusion distribution.
In Specific Aim 2, we will demonstrate that entire platform for navigation and infusion monitoring under the guidance of a newly trained neurosurgeon using a cadaver brain model. Navigation time for device alignment and insertion will be reduced to under 10 minutes. The platform will also be tested in guiding a gene delivery treatment in three in-vivo NHP models. The successful completion of this project will result in a comprehensive, integrated platform for clinically effective image-guided infusion therapies in the human brain.
The ultimate goal of this project is to develop a commercial workstation platform for guiding brain surgeries inside of an MRI scanner. The initial goal develops a specific application: speeding and simplifying MR-guided drug delivery. A scanner-independent platform obtains control of the scanner that allows us to build all the necessary imaging tasks needed for drug delivery, which are now scattered across several different computer interfaces. The proposal adds two innovations. First, rather than alternating between imaging and adjusting the orientation of surgical tools, surgeon can interact with the device while simultaneously using MRI to visualize its position. Second, once the device is in the brain at the proper location, the proposal will image the drug distribution quantitatively in real-time. The completed project will provide a platform for immediately for guiding drug delivery research trials in animal models and eventually treatments in patients.
|Kalin, Ned H; Fox, Andrew S; Kovner, Rothem et al. (2016) Overexpressing Corticotropin-Releasing Factor in the Primate Amygdala Increases Anxious Temperament and Alters Its Neural Circuit. Biol Psychiatry 80:345-55|