Inyong Kim1, Seungleal Paek2, Brian D Nelson3, Emily J Knight4, Michael P Marsh5, Allan J Bieber6, Kevin E Bennet7, Kendall H Lee8. 1. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kim.inyong@mayo.edu. 2. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: paek.seungleal@mayo.edu. 3. Medtronic Neuromodulation, 7000 Central Avenue NE, Mail Stop RCE470, Minneapolis, MN 55432, USA. Electronic address: brian.d.nelson@medtronic.com. 4. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: knight.emily@mayo.edu. 5. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: marsh.michael@mayo.edu. 6. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: bieber.allan@mayo.edu. 7. Division of Engineering, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kbennet@mayo.edu. 8. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: lee.kendall@mayo.edu.
Abstract
BACKGROUND: Systemic delivery of pharmacologic agents has led to many significant advances in the treatment of neurologic and psychiatric conditions. However, this approach has several limitations, including difficulty penetrating the blood-brain barrier and enzymatic degradation prior to reaching its intended target. Here, we describe the testing of a system allowing intraparenchymal (IPa) infusion of therapeutic agents directly to the appropriate anatomical targets, in a swine model. NEW METHOD: Five male pigs underwent 3.0T magnetic resonance (MR) guided placement of an IPa catheter into the dorso-medial putamen, using a combined system of the Leksell stereotactic arc, a Mayo-developed MRI-compatible pig head frame, and a custom-designed Fred Haer Company (FHC) delivery system. RESULTS: Our results show hemi-lateral coverage of the pig putamen is achievable from a single infusion point and that the volume of the bolus detected in each animal is uniform (1544±420mm(3)). COMPARISON WITH EXISTING METHOD: The IPa infusion system is designed to isolate the intracranial catheter from bodily-induced forces while delivering drugs and molecules into the brain tissue by convection-enhanced delivery, with minimal-to-no catheter track backflow. CONCLUSION: This study presents an innovative IPa drug delivery system, which includes a sophisticated catheter and implantable pump designed to deliver drugs and various molecules in a precise and controlled manner with limited backflow. It also demonstrates the efficacy of the delivery system, which has the potential to radically impact the treatment of a wide range of neurologic conditions. Lastly, the swine model used here has certain advantages for translation into clinical applications.
BACKGROUND: Systemic delivery of pharmacologic agents has led to many significant advances in the treatment of neurologic and psychiatric conditions. However, this approach has several limitations, including difficulty penetrating the blood-brain barrier and enzymatic degradation prior to reaching its intended target. Here, we describe the testing of a system allowing intraparenchymal (IPa) infusion of therapeutic agents directly to the appropriate anatomical targets, in a swine model. NEW METHOD: Five male pigs underwent 3.0T magnetic resonance (MR) guided placement of an IPa catheter into the dorso-medial putamen, using a combined system of the Leksell stereotactic arc, a Mayo-developed MRI-compatible pig head frame, and a custom-designed Fred Haer Company (FHC) delivery system. RESULTS: Our results show hemi-lateral coverage of the pig putamen is achievable from a single infusion point and that the volume of the bolus detected in each animal is uniform (1544±420mm(3)). COMPARISON WITH EXISTING METHOD: The IPa infusion system is designed to isolate the intracranial catheter from bodily-induced forces while delivering drugs and molecules into the brain tissue by convection-enhanced delivery, with minimal-to-no catheter track backflow. CONCLUSION: This study presents an innovative IPa drug delivery system, which includes a sophisticated catheter and implantable pump designed to deliver drugs and various molecules in a precise and controlled manner with limited backflow. It also demonstrates the efficacy of the delivery system, which has the potential to radically impact the treatment of a wide range of neurologic conditions. Lastly, the swine model used here has certain advantages for translation into clinical applications.
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