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Despite promising preclinical studies, delivery routes for maximizing cell engraftment, such as stereotactic or intrathecal injection, are invasive and carry risks of hemorrhage and infection. Recent developments in MRI-guided focused ultrasound (MRgFUS) technology have significant implications for treating focal CNS pathologies including neurodegenerative, vascular and malignant processes. MRgFUS is currently employed in the clinic for treating essential tremor and Parkinson's Disease by producing precise, incisionless, transcranial lesions. This non-invasive technology can also be modified for non-destructive applications to safely and transiently open the blood-brain barrier (BBB) to deliver a range of therapeutics, including cells. This review is meant to familiarize the neuro-interventionalist with this topic and discusses the use of MRgFUS for facilitating cellular delivery to the brain. A detailed and comprehensive description is provided on routes of cell administration, imaging strategies for targeting and tracking cellular delivery and engraftment, biophysical mechanisms of BBB enhanced permeability, supportive proof-of-concept studies, and potential for clinical translation.<\/jats:p>","DOI":"10.3389\/fneur.2021.669449","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T14:02:08Z","timestamp":1623938528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications"],"prefix":"10.3389","volume":"12","author":[{"given":"Nabid","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dheeraj","family":"Gandhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias R.","family":"Melhem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Frenkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1038\/16060","article-title":"Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient","volume":"2","author":"Piccini","year":"1999","journal-title":"Nat Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1016\/S0140-6736(00)03310-9","volume":"356","author":"Bachoud-L\u00e9vi","year":"2000","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s00401-008-0465-0","article-title":"A patient with Huntington's disease and long-surviving fetal neural transplants that developed mass lesions","volume":"117","author":"Keene","year":"2009","journal-title":"Acta Neuropathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/mt.2016.12","article-title":"MSCs genetically engineered to overexpress BDNF improve outcomes in Huntington's disease mouse models","volume":"24","author":"Pollock","year":"2016","journal-title":"Mol Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"184ra159","DOI":"10.1126\/scitranslmed.3005365","article-title":"Neural stem cell-mediated enzyme\/prodrug therapy for glioma: preclinical studies","volume":"5","author":"Aboody","year":"2013","journal-title":"Sci Transl Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.3389\/fimmu.2019.02683","article-title":"CAR-engineered NK cells for the treatment of glioblastoma: turning innate effectors into precision tools for cancer immunotherapy","volume":"10","author":"Burger","year":"2019","journal-title":"Front Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3389\/fphar.2015.00095","article-title":"Improving the safety of cell therapy with the TK-suicide gene","volume":"6","author":"Greco","year":"2015","journal-title":"Front Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell."},{"key":"B9","doi-asserted-by":"publisher","first-page":"729","DOI":"10.3389\/fcell.2020.00729","article-title":"Pluripotent stem cell therapies for Parkinson disease: present challenges and future opportunities","volume":"8","author":"Kim","year":"2020","journal-title":"Front Cell Dev Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.stem.2010.06.002","article-title":"Reprogramming of human peripheral blood cells to induced pluripotent stem cells","volume":"7","author":"Staerk","year":"2010","journal-title":"Cell Stem Cell."},{"key":"B11","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3340\/jkns.2018.0222","article-title":"Human induced pluripotent stem cells: clinical significance and applications in neurologic diseases","volume":"62","author":"Chang","year":"2019","journal-title":"J Korean Neurosurg Soc."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3377","DOI":"10.1016\/j.yexcr.2007.07.027","article-title":"C. 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