{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:30:12Z","timestamp":1780540212761,"version":"3.54.1"},"reference-count":78,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n \n Certain neurological conditions can be treated by delivering therapeutics to the thalamus, but intrathalamic perfusion properties and methods have not been tested in humans. Therefore, the aim of this study was to define the properties of intrathalamic convective gene therapy delivery by analyzing findings among patients with frontotemporal dementia (FTD) associated with granulin (\n GRN<\/jats:italic>\n ) mutation who underwent image-guided perfusion of adeno-associated virus serotype 9 (AAV9) expressing\n GRN<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Consecutive patients with FTD associated with\n GRN<\/jats:italic>\n mutations were enrolled in the ASPIRE-FTD clinical trial. Patients underwent real-time MRI-guided convective co-infusion of the bilateral thalami (1200 \u00b5L per thalamus divided equally between the anterior and posterior thalami at an infusion rate up to 15 \u00b5L\/min) with AAV9-\n GRN<\/jats:italic>\n and gadolinium-based contrast material (1 mM). Patient and infusion characteristics were assessed.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Three patients (mean age 53.0 \u00b1 18.2 years) underwent a total of 12 thalamic infusions (mean follow-up 6.0 \u00b1 3.0 months). Real-time MRI demonstrated increasing tissue volume of distribution (Vd) with increasing volume of infusion (Vi) (mean Vd-to-Vi ratio of 2.3 \u00b1 0.1, R\n 2<\/jats:sup>\n = 0.97). The mean total Vd per side was 2.8 \u00b1 1.4 cm\n 3<\/jats:sup>\n (range 2.6\u20133.2 cm\n 3<\/jats:sup>\n ). The mean thalamic coverage was 39.1% \u00b1 7.5%. Infusion shaping by varying the infusion rate and cannula position permitted excellent intrathalamic distribution (mean perfusion within the thalamus of 87.2% \u00b1 5.4%). There were no surgical complications.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n This investigation of real-time MRI-guided convective delivery provided new insights into thalamic gene therapy perfusion properties. The isotropic tissue composition, low propensity for perivascular leakage, and broad interconnectedness make the thalamus an ideal gene therapy target for a wide variety of neurological disorders.<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2025.8.jns251410","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:00:21Z","timestamp":1769083221000},"page":"682-689","source":"Crossref","is-referenced-by-count":1,"title":["Direct image-guided convective perfusion of the bilateral thalami for gene therapy in frontotemporal dementia: technical note"],"prefix":"10.3171","volume":"144","author":[{"given":"Russell R.","family":"Lonser","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus;"},{"name":"The Ohio State University Gene Therapy Institute, The Ohio State University, Columbus, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Rabon","sequence":"additional","affiliation":[{"name":"ClearPoint Neuro, Solano Beach, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Damante","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus;"},{"name":"The Ohio State University Gene Therapy Institute, The Ohio State University, Columbus, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Bradley","family":"Elder","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus;"},{"name":"The Ohio State University Gene Therapy Institute, The Ohio State University, Columbus, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslaw","family":"Zabek","sequence":"additional","affiliation":[{"name":"Interventional Neurotherapy Center, Brodno Hospital, Warsaw, Poland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Cooper","sequence":"additional","affiliation":[{"name":"AviadoBio, Ltd., London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"2","key":"b1","series-title":"Int Rev Psychiatry","first-page":"130","article-title":"The epidemiology of frontotemporal dementia","volume":"25","author":"Onyike CU","year":"2013","unstructured":"Onyike CU, Diehl-Schmid J. 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