{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:22:38Z","timestamp":1791638558082,"version":"4.3.4"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R38CA231577-01"],"award-info":[{"award-number":["R38CA231577-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01EB009041"],"award-info":[{"award-number":["5R01EB009041"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01EB009041"],"award-info":[{"award-number":["5R01EB009041"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01EB009041"],"award-info":[{"award-number":["5R01EB009041"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gary and Yael Fegel Family Foundation"},{"name":"Matheson Foundation"},{"name":"Herbert Irving Cancer Center Support Grant"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug delivery in diffuse intrinsic pontine glioma is significantly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), when combined with the administration of microbubbles can effectively open the BBB permitting the entry of drugs across the cerebrovasculature into the brainstem. Given that the utility of FUS in brainstem malignancies remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. A syngeneic orthotopic model was developed by stereotactic injection of PDGF-B<jats:sup>+<\/jats:sup>PTEN<jats:sup>\u2212\/\u2212<\/jats:sup>p53<jats:sup>\u2212\/\u2212<\/jats:sup> murine glioma cells into the pons of B6 mice. A single-element, spherical-segment 1.5\u00a0MHz ultrasound transducer driven by a function generator through a power amplifier was used with concurrent intravenous microbubble injection for tumor sonication. Mice were randomly assigned to control, FUS and double-FUS groups. Pulse and respiratory rates were continuously monitored during treatment. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen testing and sequential weight lifting measured motor function before and after sonication. A subset of animals were treated with etoposide following ultrasound. Mice were either sacrificed for tissue analysis or serially monitored for survival with daily weights. FUS successfully caused BBB opening while preserving normal cardiorespiratory and motor function. Furthermore, the degree of intra-tumoral hemorrhage and inflammation on H&amp;E in control and treated mice was similar. There was also no difference in weight loss and survival between the groups (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). Lastly, FUS increased intra-tumoral etoposide concentration by more than fivefold. FUS is a safe and feasible technique for repeated BBB opening and etoposide delivery in a preclinical pontine glioma model.<\/jats:p>","DOI":"10.1038\/s41598-021-85180-y","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:03:43Z","timestamp":1616411023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Focused ultrasound mediated blood\u2013brain barrier opening is safe and feasible in a murine pontine glioma model"],"prefix":"10.1038","volume":"11","author":[{"given":"Zachary K.","family":"Englander","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Jian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios N.","family":"Pouliopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Bendau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Upadhyayula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ing","family":"Jan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanora F.","family":"Spinazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Yoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masih","family":"Tazhibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"McQuillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony J. C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey N.","family":"Bruce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Canoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Feldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stergios","family":"Zacharoulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa E.","family":"Konofagou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chia","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"85180_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s40272-013-0033-5","volume":"15","author":"R Kebudi","year":"2013","unstructured":"Kebudi, R. & Cakir, F. B. Management of diffuse pontine gliomas in children: Recent developments. Paediatr. Drugs 15, 351\u2013362. https:\/\/doi.org\/10.1007\/s40272-013-0033-5 (2013).","journal-title":"Paediatr. Drugs"},{"key":"85180_CR2","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.cancergen.2015.04.008","volume":"208","author":"E Panditharatna","year":"2015","unstructured":"Panditharatna, E., Yaeger, K., Kilburn, L. B., Packer, R. J. & Nazarian, J. Clinicopathology of diffuse intrinsic pontine glioma and its redefined genomic and epigenomic landscape. Cancer Genet. 208, 367\u2013373. https:\/\/doi.org\/10.1016\/j.cancergen.2015.04.008 (2015).","journal-title":"Cancer Genet."},{"key":"85180_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/bf00263825","volume":"7","author":"IA Langmoen","year":"1991","unstructured":"Langmoen, I. A., Lundar, T., Storm-Mathisen, I., Lie, S. O. & Hovind, K. H. Management of pediatric pontine gliomas. Childs Nerv. Syst. 7, 13\u201315. https:\/\/doi.org\/10.1007\/bf00263825 (1991).","journal-title":"Childs Nerv. Syst."},{"key":"85180_CR4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11060-014-1448-8","volume":"119","author":"NJ Robison","year":"2014","unstructured":"Robison, N. J. & Kieran, M. W. Diffuse intrinsic pontine glioma: A reassessment. J. Neurooncol. 119, 7\u201315. https:\/\/doi.org\/10.1007\/s11060-014-1448-8 (2014).","journal-title":"J. Neurooncol."},{"key":"85180_CR5","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1002\/1097-0142(20001001)89:7<1569::aid-cncr22>3.0.co;2-0","volume":"89","author":"PG Fisher","year":"2000","unstructured":"Fisher, P. G. et al. A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities. Cancer 89, 1569\u20131576. https:\/\/doi.org\/10.1002\/1097-0142(20001001)89:7%3c1569::aid-cncr22%3e3.0.co;2-0 (2000).","journal-title":"Cancer"},{"key":"85180_CR6","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/S1470-2045(18)30322-X","volume":"19","author":"MM Souweidane","year":"2018","unstructured":"Souweidane, M. M. et al. Convection-enhanced delivery for diffuse intrinsic pontine glioma: A single-centre, dose-escalation, phase 1 trial. Lancet Oncol. 19, 1040\u20131050. https:\/\/doi.org\/10.1016\/S1470-2045(18)30322-X (2018).","journal-title":"Lancet Oncol."},{"key":"85180_CR7","doi-asserted-by":"publisher","first-page":"289","DOI":"10.3171\/2012.10.PEDS12142","volume":"11","author":"RC Anderson","year":"2013","unstructured":"Anderson, R. C. et al. Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children. J. Neurosurg. Pediatr. 11, 289\u2013295. https:\/\/doi.org\/10.3171\/2012.10.PEDS12142 (2013).","journal-title":"J. Neurosurg. Pediatr."},{"key":"85180_CR8","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1200\/JCO.2000.18.6.1246","volume":"18","author":"A Broniscer","year":"2000","unstructured":"Broniscer, A., Leite, C. C., Lanchote, V. L., Machado, T. M. & Cristofani, L. M. Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: Results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J. Clin. Oncol. 18, 1246\u20131253. https:\/\/doi.org\/10.1200\/JCO.2000.18.6.1246 (2000).","journal-title":"J. Clin. Oncol."},{"key":"85180_CR9","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1002\/(sici)1097-0142(20000201)88:3<685::aid-cncr27>3.0.co;2-k","volume":"88","author":"E Bouffet","year":"2000","unstructured":"Bouffet, E. et al. Radiotherapy followed by high dose busulfan and thiotepa: A prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88, 685\u2013692. https:\/\/doi.org\/10.1002\/(sici)1097-0142(20000201)88:3%3c685::aid-cncr27%3e3.0.co;2-k (2000).","journal-title":"Cancer"},{"key":"85180_CR10","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/bf00599203","volume":"36","author":"T Fujiwara","year":"1994","unstructured":"Fujiwara, T. et al. Intra-arterial chemotherapy for brain stem glioma: Report of four cases. Neuroradiology 36, 74\u201379. https:\/\/doi.org\/10.1007\/bf00599203 (1994).","journal-title":"Neuroradiology"},{"key":"85180_CR11","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1148\/radiol.2202001804","volume":"220","author":"K Hynynen","year":"2001","unstructured":"Hynynen, K., McDannold, N., Vykhodtseva, N. & Jolesz, F. A. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220, 640\u2013646. https:\/\/doi.org\/10.1148\/radiol.2202001804 (2001).","journal-title":"Radiology"},{"key":"85180_CR12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuroimage.2004.06.046","volume":"24","author":"K Hynynen","year":"2005","unstructured":"Hynynen, K., McDannold, N., Sheikov, N. A., Jolesz, F. A. & Vykhodtseva, N. Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 24, 12\u201320. https:\/\/doi.org\/10.1016\/j.neuroimage.2004.06.046 (2005).","journal-title":"Neuroimage"},{"key":"85180_CR13","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/j.ultrasmedbio.2005.07.010","volume":"31","author":"N McDannold","year":"2005","unstructured":"McDannold, N., Vykhodtseva, N., Raymond, S., Jolesz, F. A. & Hynynen, K. MRI-guided targeted blood-brain barrier disruption with focused ultrasound: Histological findings in rabbits. Ultrasound Med. Biol. 31, 1527\u20131537. https:\/\/doi.org\/10.1016\/j.ultrasmedbio.2005.07.010 (2005).","journal-title":"Ultrasound Med. Biol."},{"key":"85180_CR14","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2182","author":"DY Zhang","year":"2019","unstructured":"Zhang, D. Y. et al. Ultrasound-mediated delivery of paclitaxel for Glioma: A comparative study of distribution, toxicity, and efficacy of albumin-bound versus cremophor formulations. Clin. Cancer Res. https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-2182 (2019).","journal-title":"Clin. Cancer Res."},{"key":"85180_CR15","doi-asserted-by":"publisher","first-page":"E8717","DOI":"10.1073\/pnas.1807105115","volume":"115","author":"CD Arvanitis","year":"2018","unstructured":"Arvanitis, C. D. et al. Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption. Proc. Natl. Acad. Sci. U S A 115, E8717\u2013E8726. https:\/\/doi.org\/10.1073\/pnas.1807105115 (2018).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"85180_CR16","doi-asserted-by":"publisher","first-page":"6284","DOI":"10.7150\/thno.35892","volume":"9","author":"N McDannold","year":"2019","unstructured":"McDannold, N. et al. Acoustic feedback enables safe and reliable carboplatin delivery across the blood-brain barrier with a clinical focused ultrasound system and improves survival in a rat glioma model. Theranostics 9, 6284\u20136299. https:\/\/doi.org\/10.7150\/thno.35892 (2019).","journal-title":"Theranostics"},{"key":"85180_CR17","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jconrel.2018.12.009","volume":"295","author":"A Papachristodoulou","year":"2019","unstructured":"Papachristodoulou, A. et al. Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes. J. Control Release 295, 130\u2013139. https:\/\/doi.org\/10.1016\/j.jconrel.2018.12.009 (2019).","journal-title":"J. Control Release"},{"key":"85180_CR18","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s10439-018-02141-9","volume":"47","author":"Z Pi","year":"2019","unstructured":"Pi, Z. et al. Sonodynamic therapy on intracranial glioblastoma xenografts using sinoporphyrin sodium delivered by ultrasound with microbubbles. Ann. Biomed. Eng. 47, 549\u2013562. https:\/\/doi.org\/10.1007\/s10439-018-02141-9 (2019).","journal-title":"Ann. Biomed. Eng."},{"key":"85180_CR19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1148\/radiol.10090699","volume":"255","author":"HL Liu","year":"2010","unstructured":"Liu, H. L. et al. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology 255, 415\u2013425. https:\/\/doi.org\/10.1148\/radiol.10090699 (2010).","journal-title":"Radiology"},{"key":"85180_CR20","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1158\/1078-0432.CCR-18-3643","volume":"25","author":"A Idbaih","year":"2019","unstructured":"Idbaih, A. et al. Safety and feasibility of repeated and transient blood-brain barrier disruption by pulsed ultrasound in patients with recurrent glioblastoma. Clin. Cancer Res. 25, 3793\u20133801. https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-3643 (2019).","journal-title":"Clin. Cancer Res."},{"key":"85180_CR21","doi-asserted-by":"publisher","first-page":"343re342","DOI":"10.1126\/scitranslmed.aaf6086","volume":"8","author":"A Carpentier","year":"2016","unstructured":"Carpentier, A. et al. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci. Transl. Med. 8, 343re342. https:\/\/doi.org\/10.1126\/scitranslmed.aaf6086 (2016).","journal-title":"Sci. Transl. Med."},{"issue":"1","key":"85180_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-36340-0","volume":"9","author":"T Mainprize","year":"2019","unstructured":"Mainprize, T. et al. Blood-brain barrier opening in primary brain tumors with non-invasive MR-guided focused ultrasound: a clinical safety and feasibility study. Sci. Rep. 9(1), 1\u20137. https:\/\/doi.org\/10.1038\/s41598-018-36340-0 (2019).","journal-title":"Sci. Rep."},{"key":"85180_CR23","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jconrel.2018.05.039","volume":"283","author":"D Ye","year":"2018","unstructured":"Ye, D. et al. Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons. J. Control Release 283, 143\u2013150. https:\/\/doi.org\/10.1016\/j.jconrel.2018.05.039 (2018).","journal-title":"J. Control Release"},{"key":"85180_CR24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.jconrel.2018.07.020","volume":"286","author":"D Ye","year":"2018","unstructured":"Ye, D. et al. Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain. J. Control Release 286, 145\u2013153. https:\/\/doi.org\/10.1016\/j.jconrel.2018.07.020 (2018).","journal-title":"J. Control Release"},{"key":"85180_CR25","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jconrel.2018.05.005","volume":"281","author":"S Alli","year":"2018","unstructured":"Alli, S. et al. Brainstem blood brain barrier disruption using focused ultrasound: A demonstration of feasibility and enhanced doxorubicin delivery. J. Control Release 281, 29\u201341. https:\/\/doi.org\/10.1016\/j.jconrel.2018.05.005 (2018).","journal-title":"J. Control Release"},{"key":"85180_CR26","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s11060-013-1082-x","volume":"112","author":"AM Sonabend","year":"2013","unstructured":"Sonabend, A. M. et al. Murine cell line model of proneural glioma for evaluation of anti-tumor therapies. J. Neurooncol. 112, 375\u2013382. https:\/\/doi.org\/10.1007\/s11060-013-1082-x (2013).","journal-title":"J. Neurooncol."},{"key":"85180_CR27","doi-asserted-by":"publisher","first-page":"5396","DOI":"10.7150\/thno.28717","volume":"9","author":"ME Karakatsani","year":"2019","unstructured":"Karakatsani, M. E. et al. Unilateral focused ultrasound-induced blood-brain barrier opening reduces phosphorylated tau from The rTg4510 mouse model. Theranostics 9, 5396\u20135411. https:\/\/doi.org\/10.7150\/thno.28717 (2019).","journal-title":"Theranostics"},{"key":"85180_CR28","doi-asserted-by":"publisher","first-page":"6941","DOI":"10.1088\/0031-9155\/59\/22\/6941","volume":"59","author":"AN Pouliopoulos","year":"2014","unstructured":"Pouliopoulos, A. N., Bonaccorsi, S. & Choi, J. J. Exploiting flow to control the in vitro spatiotemporal distribution of microbubble-seeded acoustic cavitation activity in ultrasound therapy. Phys. Med. Biol. 59, 6941\u20136957. https:\/\/doi.org\/10.1088\/0031-9155\/59\/22\/6941 (2014).","journal-title":"Phys. Med. Biol."},{"key":"85180_CR29","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ultrasmedbio.2019.09.010","volume":"46","author":"AN Pouliopoulos","year":"2020","unstructured":"Pouliopoulos, A. N. et al. A clinical system for non-invasive blood-brain barrier opening using a neuronavigation-guided single-element focused ultrasound transducer. Ultrasound Med. Biol. 46, 73\u201389. https:\/\/doi.org\/10.1016\/j.ultrasmedbio.2019.09.010 (2020).","journal-title":"Ultrasound Med. Biol."},{"key":"85180_CR30","doi-asserted-by":"publisher","first-page":"46689","DOI":"10.1038\/srep46689","volume":"7","author":"SK Wu","year":"2017","unstructured":"Wu, S. K. et al. Characterization of different microbubbles in assisting focused ultrasound-induced blood-brain barrier opening. Sci. Rep. 7, 46689. https:\/\/doi.org\/10.1038\/srep46689 (2017).","journal-title":"Sci. Rep."},{"key":"85180_CR31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.ultrasmedbio.2006.07.018","volume":"33","author":"JJ Choi","year":"2007","unstructured":"Choi, J. J., Pernot, M., Small, S. A. & Konofagou, E. E. Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice. Ultrasound Med. Biol. 33, 95\u2013104. https:\/\/doi.org\/10.1016\/j.ultrasmedbio.2006.07.018 (2007).","journal-title":"Ultrasound Med. Biol."},{"key":"85180_CR32","first-page":"277","volume":"152","author":"W Kondziella","year":"1964","unstructured":"Kondziella, W. A new method for the measurement of muscle relaxation in white mice. Arch. Int. Pharmacodyn. Ther. 152, 277\u2013284 (1964).","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"85180_CR33","doi-asserted-by":"publisher","DOI":"10.3791\/2610","author":"RM Deacon","year":"2013","unstructured":"Deacon, R. M. Measuring the strength of mice. J. Vis. Exp. https:\/\/doi.org\/10.3791\/2610 (2013).","journal-title":"J. Vis. Exp."},{"key":"85180_CR34","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3389\/fonc.2019.00031","volume":"9","author":"BT Himes","year":"2019","unstructured":"Himes, B. T., Zhang, L. & Daniels, D. J. Treatment strategies in diffuse midline gliomas with the H3K27M mutation: The role of convection-enhanced delivery in overcoming anatomic challenges. Front. Oncol. 9, 31. https:\/\/doi.org\/10.3389\/fonc.2019.00031 (2019).","journal-title":"Front. Oncol."},{"key":"85180_CR35","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s11060-015-1969-9","volume":"126","author":"E Subashi","year":"2016","unstructured":"Subashi, E. et al. Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma. J. Neurooncol. 126, 243\u2013251. https:\/\/doi.org\/10.1007\/s11060-015-1969-9 (2016).","journal-title":"J. Neurooncol."},{"key":"85180_CR36","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.bcp.2009.06.001","volume":"78","author":"R Zhao","year":"2009","unstructured":"Zhao, R. & Pollack, G. M. Regional differences in capillary density, perfusion rate, and P-glycoprotein activity: A quantitative analysis of regional drug exposure in the brain. Biochem. Pharmacol. 78, 1052\u20131059. https:\/\/doi.org\/10.1016\/j.bcp.2009.06.001 (2009).","journal-title":"Biochem. Pharmacol."},{"key":"85180_CR37","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s00280-005-0172-7","volume":"58","author":"K Warren","year":"2006","unstructured":"Warren, K. et al. Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: A report from the Children\u2019s Oncology Group. Cancer Chemother. Pharmacol. 58, 343\u2013347. https:\/\/doi.org\/10.1007\/s00280-005-0172-7 (2006).","journal-title":"Cancer Chemother. Pharmacol."},{"key":"85180_CR38","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1023\/a:1016034910875","volume":"58","author":"RJ Lutz","year":"2002","unstructured":"Lutz, R. J., Warren, K., Balis, F., Patronas, N. & Dedrick, R. L. Mixing during intravertebral arterial infusions in an in vitro model. J. Neurooncol. 58, 95\u2013106. https:\/\/doi.org\/10.1023\/a:1016034910875 (2002).","journal-title":"J. Neurooncol."},{"key":"85180_CR39","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s40478-018-0614-1","volume":"6","author":"D Castel","year":"2018","unstructured":"Castel, D. et al. Transcriptomic and epigenetic profiling of \u201cdiffuse midline gliomas, H3 K27M-mutant\u201d discriminate two subgroups based on the type of histone H3 mutated and not supratentorial or infratentorial location. Acta Neuropathol. Commun. 6, 117. https:\/\/doi.org\/10.1186\/s40478-018-0614-1 (2018).","journal-title":"Acta Neuropathol. Commun."},{"key":"85180_CR40","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41582-019-0220-2","volume":"15","author":"AM Molinaro","year":"2019","unstructured":"Molinaro, A. M., Taylor, J. W., Wiencke, J. K. & Wrensch, M. R. Genetic and molecular epidemiology of adult diffuse glioma. Nat. Rev. Neurol. 15, 405\u2013417. https:\/\/doi.org\/10.1038\/s41582-019-0220-2 (2019).","journal-title":"Nat. Rev. Neurol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85180-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85180-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85180-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T05:37:11Z","timestamp":1670045831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85180-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["85180"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-85180-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"16 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Spinazzi has a direct family member who is employed by\u00a0Bracco Group. Dr. Wang reports personal fees and non-financial support from AbbVie, personal fees from AstraZeneca, personal fees from Cancer Panels, personal fees from Doximity, personal fees and non-financial support from Elekta, personal fees and non-financial support from Merck, personal fees and non-financial support from Novocure, personal fees and non-financial support from RTOG Foundation, personal fees from Rutgers, personal fees from University of Iowa, personal fees from Wolters Kluwer, grants and non-financial support from Genentech, outside the submitted work. Dr. Konofagou reports equity and non-financial support from Vesselon. The remaining authors do not have any competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6521"}}