The overall goal of this project is to develop a new minimally invasive medical device: a working prototype catheter that is remotely magnetically controlled for use in the endovascular interventional magnetic resonance imaging (MRI) environment. Several major public health threats, including ischemic stroke, brain aneurysm, solid tumors, atherosclerosis, and cardiac arrhythmias are currently diagnosed and treated endovascularly under x-ray fluoroscopic guidance. Although x-ray fluoroscopy has high spatial and temporal resolution, it only visualizes blood vessels as opposed to the soft tissues and organs ultimately supplied by those blood vessels. Whereas x-ray fluoroscopy uses ionizing radiation, which in large doses can have deleterious effects both on patients and health care providers;MRI does not use ionizing radiation. Performing endovascular procedures under MRI guidance is a key application of the growing field of interventional MRI. Fast yet high resolution MR imaging techniques have been developed in recent years, allowing frame rates comparable to those achieved with x-ray fluoroscopy. Performing procedures under MRI allows use of the wide array of MR anatomic and physiologic imaging techniques during an intervention: diffusion weighted imaging to evaluate for tissue infarction, perfusion imaging to assess for organ blood flow, high resolution anatomic imaging to visualize tissues surrounding and downstream from a catheterized blood vessel. Having such MRI information can help guide the interventional physician's decisions as to when a desired therapeutic result has been achieved or when an undesired procedural complication has occurred, whereas under x-ray guidance, parameters such as perfusion and infarction can only be inferred. If vascular interventions can be performed under MRI guidance, then real time physiologic MR imaging can be used to augment intraprocedural decision making, potentially allowing new patients to receive endovascular therapy and improving clinical outcomes. In addition to the imaging advantages of MRI, the strong homogeneous magnetic (B0) field inside the MRI scanner provides a unique opportunity for catheter tip navigation by remote control. If a tiny magnetic moment is created on the tip of the catheter by application of a small electrical current to copper coils on the catheter tip, then the tip of the catheter will move to align with the bore of the MRI scanner (the direction of the B0field). If one such coil is placed at the catheter tip, it can be deflected in one plane by remote control or turned by the practitioner's hand to deflect in another plane. If three such coils are placed on the catheter tip, then remote controlled deflection can be achieved in three dimensions even without the hand of the interventionalist. This technology potentially will allow better navigation of small, tortuous blood vessels that are currently difficult to catheterize due to build-up of friction at the many vascular bends between the femoral access site and the target blood vessel. Low levels of current supplied to the catheter coils also permits active visualization of the catheter tip, which otherwise can be difficult to see in the MR environment. We previously developed a laser lathe lithography technique to synthesize catheters tipped with copper coils in up to three orthogonal axes. We used real-time MRI techniques to visualize the catheter tip and navigate simple vascular phantoms in a clinical MRI scanner. We measured heating within the catheter and its surroundings both in vitro and in vivo. We also derived and validated equations to characterize the relationship between catheter coil geometry, applied current, catheter stiffness, magnetic field strength, and resulting catheter tip deflections. In this new proposal, we will build upon earlier research with the following specific aims: 1. Specific Aim 1: Refine catheter shaft and tip design to improve functionality; 2. Specific Aim 2: Evaluate MR imaging strategies to optimize catheter visualization and minimize artifacts; 3. Specific Aim 3: Test catheter navigation and imaging in vitro in the 1.5 T and 3.0 T MRI environments; 4. Specific Aim 4: Evaluate in vivo catheter navigation and imaging in animal models at 1.5 T; 5. Specific Aim 5: Assess catheter safety at 1.5 T; 6. Specific Aim 6: Assess the performance of the catheter system in animal models of key MR-guided interventions: thrombolysis (as for acute ischemic stroke treatment) and particulate embolization for controlled tissue infarction (as for tumor treatment). At the end of the proposed project period, the magnetic catheter system will be a viable device for improving the speed and efficacy of interventions performed in the MR environment. It thus will stand to revolutionize the clinical treatment of diseases that would benefit from real time physiologic tissue monitoring during endovascular therapy. PUBLIC HEALTH RELEVANCE: Stroke, cancer, and cardiovascular disease are the major causes of death and disability in the United States and MRI plays an important role in the diagnosis and evaluation of these disorders. The technology to be developed in this project exploits the magnetic environment of the MRI scanner to manipulate catheters and therapeutic devices, thereby transforming MRI into a therapeutic modality as well as a diagnostic one. This could ultimately lead to safer and more efficacious treatment strategies for several major causes of morbidity and mortality.