title: Access to the brain parenchyma using endovascular techniques and a micro-working channel.
abstract: OBJECTIVE Several older studies report a low risk for parenchymal access to the CNS by surgical techniques. In more recent studies, including those with post-puncture CT scans, there are indications that the risk of bleeding might approach 8%. New therapies, such as those that use viral vectors, modified mRNA, or cell transplantation, will probably warrant more parenchymal access to the CNS. Other minimally invasive routes might then be tempting to explore. This study was designed in 2 parts to address the possibility of using the endovascular route. The first aim was to test the ability to create a parenchymal micro-working channel to the CNS in macaque monkeys through the vessel wall. Second, the biocompatibility of a device-associated, detached, distal securing plug that was made of nitinol was investigated in swine for 1 year. METHODS Trans-vessel wall intervention in the middle cerebral artery and associated cerebral parenchyma was performed in 4 rhesus macaque monkeys using a full clinical angiography suite. A contrast agent and methylene blue were injected to test the working channel and then detached at the distal end to act as a securing plug through the vessel wall. One-year follow-ups were also performed using angiography and histological analysis in 10 swine with 24 implants that were distributed in the external carotid artery tree. RESULTS The cerebral interventions were performed without acute bleeding. Both the contrast agent and methylene blue were infused into the brain parenchyma and subarachnoidal space via the endovascular micro-working channel (7 injections in 4 animals). In the 1-year follow-up period, the implant that was left in the external carotid vessel wall in the swine was covered by the endothelium, which was followed by dislodgement just outside the blood vessel with thin capsule formation. No stenosis in the artery was detected on 1-year angiography. The animals showed normal behavior and blood sample results during the follow-up period. This is the first histological demonstration of nitinol biocompatibility when the implant is positioned through an arterial wall and indicates that the trans-vessel wall technique is not comparable with stent placement and its ability to induce intimal hyperplasia and restenosis. CONCLUSIONS This study demonstrates that the trans-vessel wall technique is applicable to brain intervention in macaque monkeys, providing a micro-working channel for delivery or sampling. The long-term follow-up study of the detached device in swine showed no clinical or biochemical complications and a normal angiography appearance.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet.|Department of Neuroradiology, Karolinska University Hospital, Stockholm.
authors.forename: Johan
authors.initials: J
authors.lastname: Lundberg
authors.affiliation: Department of Prosthodontics/Dental Materials, Science, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Sweden; and.
authors.forename: Carina B
authors.initials: CB
authors.lastname: Johansson
authors.affiliation: Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jonsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet.|Department of Neuroradiology, Karolinska University Hospital, Stockholm.
authors.forename: Staffan
authors.initials: S
authors.lastname: Holmin
mesh_terms: D000497:Alloys; D000818:Animals; D001921:Brain / Q000601:surgery*; D057510:Endovascular Procedures / Q000379:methods*; D008253:Macaca mulatta; D020768:Middle Cerebral Artery / Q000601:surgery*; D000072356:Parenchymal Tissue / Q000601:surgery*; D015607:Stents; D013552:Swine
chemical_list: D000497:Alloys; C013616:nitinol
keywords: ECA = external carotid artery; endovascular; macaque; minimal invasive; nitinol; parenchymal puncture; swine; vascular disorders