{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:14:55Z","timestamp":1782306895117,"version":"3.54.5"},"reference-count":88,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Magnetic Resonance Imaging"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Regulatory bodies in the U.S. and Europe recently approved a gene therapy for aromatic L\u2010amino acid decarboxylase (AADC) deficiency, a rare neurologic disorder where a genetic mutation prevents dopamine production in the brain. Affected children fail to develop normal motor and cognitive functions. MRI\u2010guided intraparenchymal delivery of AADC gene therapy to localized gray matter regions\u2014specifically the substantia nigra and ventral tegmental area\u2014has enabled the brain to produce dopamine, resulting in dramatic improvements in physical and cognitive outcomes. The need to target only a small brain region simplifies the surgical approach. However, gene therapy for broader neurodegenerative conditions has progressed more slowly than expected, despite significant global investment. Clinical efficacy depends heavily on the accurate delivery of gene therapeutics via direct brain infusion, cerebrospinal fluid (CSF) administration, or both. Inadequate image guidance during clinical trials makes it difficult to distinguish between true drug inefficacy and delivery failure. We highlight how increasing use of MRI for pre\u2010surgical simulation and real\u2010time therapy monitoring is accelerating gene therapy development for neurological diseases. This manuscript explores MRI's role in guiding intraparenchymal gene delivery, particularly using Convection Enhanced Delivery (CED). MRI contributes across the treatment timeline\u2014from pre\u2010surgical planning and infusion guidance to validating therapeutic coverage. We describe how MRI supports controlled therapeutic distribution for localized treatments and its potential to enable broader distributions needed for correcting widespread genetic anomalies. We also detail how structural and anatomical MRI sequences (T1, T2, Time of Flight, and Diffusion Tensor Imaging (DTI)) can help model likely infusion distributions. Finally, we provide an outlook on how advanced DTI\u2010based algorithms and poroelastic theory could further improve modeling of infusion dynamics. Current MRI\u2010based technologies can be integrated and enhanced to improve CED effectiveness, especially in very young pediatric patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evidence Level<\/jats:title><jats:p>1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Technical Efficacy<\/jats:title><jats:p>Stage 4.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmri.29804","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T06:24:41Z","timestamp":1745216681000},"page":"1280-1295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>MR<\/scp>\u2010Guidance of Gene Therapy for Brain Diseases: Moving From Palliative Treatment to Cures"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5044-8757","authenticated-orcid":false,"given":"Dalton H.","family":"Bermudez","sequence":"first","affiliation":[{"name":"Department of Medical Physics UW Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7122-8438","authenticated-orcid":false,"given":"Thomas","family":"Lilieholm","sequence":"additional","affiliation":[{"name":"Department of Medical Physics UW Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter F.","family":"Block","sequence":"additional","affiliation":[{"name":"Department of Medical Physics UW Madison  Madison Wisconsin USA"},{"name":"Department of Biomedical Engineering UW Madison  Madison Wisconsin USA"},{"name":"Department of Radiology UW Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00434"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46080499"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297923120179"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2023.3852"},{"key":"e_1_2_14_6_1","unstructured":"L.Luxner \u201cFDA Industry Officials Predict 2024 Will Be \u2018Breakout Year\u2019 for Gene Therapy Approvals \u201d2024."},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434\u2010024\u201000503\u20108"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.06.035"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2022.03.010"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050942510"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302615"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2017.0069"},{"key":"e_1_2_14_13_1","unstructured":"Editas Medicine Inc \u201cSingle Ascending Dose Study in Participants With LCA10 \u201d https:\/\/clinicaltrials.gov\/study\/NCT03872479."},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3171\/2014.10.JNS14229"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2024.09.002"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2002.97.4.0905"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2005.16.1028"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3171\/2009.11.JNS091052"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mric.2015.05.003"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb5413"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010322904"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1179\/016164110X12816242542652"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.022"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1088\/2057\u20101976\/aa5a77"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2012.681463"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.11.012"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2013.47"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1522\u20102586(199904)9:4<596::aid\u2010jmri14>3.0.co;2\u2010t"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/1522\u20102586(200101)13:1<12::aid\u2010jmri1002>3.0.co"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/1522\u20102586(200101)13:1<16::aid\u2010jmri1003>3.0.co;2\u2010b"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.1065"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.1880080136"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.114"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.29426"},{"key":"e_1_2_14_35_1","unstructured":"M.Brady R.Raghavan P.Wang et\u00a0al. \u201cReal\u2010Time MR Brain Infusion Monitoring Enables Accurate Prediction of End Drug Distribution \u201dISMRM."},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21273"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mric.2005.04.001"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21318"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e31822f4a91"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2022.02.095"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.3171\/2015.4.JNS15173"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2022.109643"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.23771"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.3171\/2011.5.JNS11246"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.01.010"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2013.4"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e3182181ba8"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.06.0428"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00335"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2024.1376587"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.210559"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2007"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031\u20109155\/56\/19\/003"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.6.H2726"},{"key":"e_1_2_14_55_1","doi-asserted-by":"crossref","unstructured":"M.Brady R.Raghavan andJ.Sampson \u201cDeterminants of Intraparenchymal Infusion Distributions: Modeling and Analyses of Human Glioblastoma Trials \u201d12 no.9(2020) https:\/\/doi.org\/10.3390\/pharmaceutics12090895.","DOI":"10.3390\/pharmaceutics12090895"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde\u20102016\u20100016"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28663"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26518"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171473898"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/eng2.12108"},{"key":"e_1_2_14_61_1","first-page":"22","article-title":"Controlling Brain Infusion Distributions: Moving From Surgical Planning to Real\u2010Time MR Guidance","volume":"25","author":"Brady M.","year":"2017","journal-title":"Proceedings of the International Society for Magnetic Resonance in Medicine"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.04.018"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.29537"},{"key":"e_1_2_14_64_1","unstructured":"D. H.BermudezandW.Bloch \u201cNew Trick for Bssfp MRI: Simplified Sulci Detection for Predictive Mapping of Intraparenchymal Brain Therapies.\u201d2024 InAAPM 66th Annual Meeting & Exhibition 2024."},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5145\u201007.2008"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27286"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27019"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.116835"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.3171\/foc.2006.20.4.7"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24760"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234\u2010004\u20101241\u2010z"},{"key":"e_1_2_14_72_1","volume-title":"Quantifying Inter\u2010Region Variation in Hydraulic Parameters for Guiding Convection\u2010Enhanced Delivery in the Brain With Diffusion Imaging","author":"Lilieholm T.","year":"2024"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.29248"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.02.018"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010023\u201001327\u20102"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30318-1"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.29040"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.rev.2023\u20100175"},{"key":"e_1_2_14_79_1","unstructured":"I.Heukensfeldt Jansen N.Abad A.Ajala et\u00a0al. \u201cOptimization of Simultaneous Coherent\/Incoherent Motion Imaging (SCIMI): Combined Diffusion and Velocimetry for Glymphatic Circulation \u201d2024 ISMRM."},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018746"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27059"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27806"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.29389"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.29056"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28747"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27192"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.01.046"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.01.051"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci15010079"}],"container-title":["Journal of Magnetic Resonance Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.29804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:25:17Z","timestamp":1759958717000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmri.29804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,21]]},"references-count":88,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jmri.29804"],"URL":"https:\/\/doi.org\/10.1002\/jmri.29804","archive":["Portico"],"relation":{},"ISSN":["1053-1807","1522-2586"],"issn-type":[{"value":"1053-1807","type":"print"},{"value":"1522-2586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,21]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}