Significance: We propose to extend and customize inseRT MRI?s Real-Time MR image-guided surgical platform, originally developed for cerebral biopsy and direct injection cancer therapies, to overcome shortcomings in CT guidance of a promising new thrombolytic therapy for intracerebral hemorrhage (ICH). ICH is a devastating injury creating stroke-like outcomes in 100,000 people in the USA each year. Damage from mechanical effects of the blood clot in the brain is followed by damage due to exposure to decaying blood products and edema, with little promise of rehabilitation afterwards for surviving victims. Minimal Invasive Surgery (MIS) approaches can dissolve blood clots by delivering recombinant tissue-type plasminogen activator (rtPA) directly into clots through rigid catheter insertions, and have shown significant promise in NIH Phase I and II Trials. These Trials have reduced long-term neurological deficits by removing significant portions of the clots with few procedure-related side effects. However, the extent of clot reduction and thus treatment benefits vary significantly between patients due to lack of monitoring technology to guide clot removal while maintaining a desirable safety profile. In current practice, a catheter is placed into the deep end of the clot using stereotactic guidance. rtPA is administered in moderate, uniform doses (1 ml) approximately every 8 hours as the portion of the clot that dissolves is allowed to drain. The treatment is iterated up to 9 times over 3-5 days. CT images are currently acquired periodically to monitor gross clot size, depicted as an iso-intense region in CT. Without knowledge of where the rtPA is distributed, the patient must be dosed conservatively to avoid a re-hemorrhage. We have recognized how our expertise in MR-guided brain infusions can drive the drug further into the clot while monitoring its spatial distribution. This advance will reduce the number iterations, ultimately to a single iteration, while reducing outcome variations and maintaining safety. Goals: We will create an kitted solution of guideports, catheters, and corresponding guidance and monitoring software for ICH evacuation. We will exploit MRI?s ability to differentiate clot components to immediately extract plasma during catheter placement to minimize secondary brain damage. We will then translate the use of infusion catheters, designed first for brain cancer infusions, to drive clot-busting drugs safely over a much larger distribution zone by 3D visualization of rtPA distribution within the clot. The new application will exploit inseRT MRI?s ability to control MRI scanner image acquisition and visualize infusion feedback in true real-time while eliminating the complexity of using a diagnostic MR scanner for an interventional application. !
Recent image-guided therapies have shown the capability to reduce the clot volume, brain edema, and thus long-term neurological problems suffered by strokes started by a brain bleed. But as computed tomography (CT), the current method of guiding clot-busting drugs into the clot, doesn?t permit the surgeon to visualize the changing makeup of the clot or map where clot-busting drugs are going, surgeons are limited to following conservative treatment rules. As magnetic resonance (MR) imaging does not have these weaknesses, we propose to empower surgeons to remove more of the clot in less time by adapting our Real-time MR guidance platform and novel catheters. We will dissolve the clot faster while maintaining safety by visualizing where clot-busting drugs are moving in the clot.
