{"id":"https://openalex.org/W7201845293","doi":"https://doi.org/10.1093/noajnl/vdag161.022","title":"DSAI-04 FOCUSED ULTRASOUND-ENHANCED DRUG DELIVERY TO THE HUMAN BRAIN AND BRAIN TUMORS: MECHANISTIC AND QUANTITATIVE INSIGHTS FROM PHYSIOLOGICALLY BASED CNS PHARMACOKINETIC MODELING","display_name":"DSAI-04 FOCUSED ULTRASOUND-ENHANCED DRUG DELIVERY TO THE HUMAN BRAIN AND BRAIN TUMORS: MECHANISTIC AND QUANTITATIVE INSIGHTS FROM PHYSIOLOGICALLY BASED CNS PHARMACOKINETIC MODELING","publication_year":2026,"publication_date":"2026-08-01","ids":{"openalex":"https://openalex.org/W7201845293","doi":"https://doi.org/10.1093/noajnl/vdag161.022"},"language":"en","primary_location":{"id":"doi:10.1093/noajnl/vdag161.022","doi":"https://doi.org/10.1093/noajnl/vdag161.022","is_oa":true,"landing_page_url":"https://doi.org/10.1093/noajnl/vdag161.022","pdf_url":null,"source":{"id":"https://openalex.org/S4210237914","display_name":"Neuro-Oncology Advances","issn_l":"2632-2498","issn":["2632-2498"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","ki-jl-1","norway-1","poland-20","russia-white-list-4"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neuro-Oncology Advances","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1093/noajnl/vdag161.022","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Andrew Wu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrew Wu","raw_affiliation_strings":["Johns Hopkins Whiting School of Engineering , Baltimore,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins Whiting School of Engineering , Baltimore,","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083325219","display_name":"Charuka D. Wickramasinghe","orcid":"https://orcid.org/0009-0007-8002-0632","observed_orcids":["https://orcid.org/0009-0007-8002-0632"]},"institutions":[{"id":"https://openalex.org/I185443292","display_name":"Wayne State University","ror":"https://ror.org/01070mq45","country_code":"US","type":"education","lineage":["https://openalex.org/I185443292"]},{"id":"https://openalex.org/I4210090317","display_name":"The Barbara Ann Karmanos Cancer Institute","ror":"https://ror.org/00ee40h97","country_code":"US","type":"facility","lineage":["https://openalex.org/I2800590384","https://openalex.org/I4210090317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Charuka Wickramasinghe","raw_affiliation_strings":["Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,","institution_ids":["https://openalex.org/I185443292","https://openalex.org/I4210090317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5128900337","display_name":"Yuanyuan Jiang","orcid":"https://orcid.org/0009-0007-5779-0946","observed_orcids":["https://orcid.org/0009-0007-5779-0946"]},"institutions":[{"id":"https://openalex.org/I185443292","display_name":"Wayne State University","ror":"https://ror.org/01070mq45","country_code":"US","type":"education","lineage":["https://openalex.org/I185443292"]},{"id":"https://openalex.org/I4210090317","display_name":"The Barbara Ann Karmanos Cancer Institute","ror":"https://ror.org/00ee40h97","country_code":"US","type":"facility","lineage":["https://openalex.org/I2800590384","https://openalex.org/I4210090317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yuanyuan Jiang","raw_affiliation_strings":["Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,","institution_ids":["https://openalex.org/I185443292","https://openalex.org/I4210090317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102220426","display_name":"Xun Bao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I185443292","display_name":"Wayne State University","ror":"https://ror.org/01070mq45","country_code":"US","type":"education","lineage":["https://openalex.org/I185443292"]},{"id":"https://openalex.org/I4210090317","display_name":"The Barbara Ann Karmanos Cancer Institute","ror":"https://ror.org/00ee40h97","country_code":"US","type":"facility","lineage":["https://openalex.org/I2800590384","https://openalex.org/I4210090317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xun Bao","raw_affiliation_strings":["Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,","institution_ids":["https://openalex.org/I185443292","https://openalex.org/I4210090317"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5004418649","display_name":"Jing Li","orcid":"https://orcid.org/0000-0002-9924-1386","observed_orcids":["https://orcid.org/0000-0002-9924-1386"]},"institutions":[{"id":"https://openalex.org/I185443292","display_name":"Wayne State University","ror":"https://ror.org/01070mq45","country_code":"US","type":"education","lineage":["https://openalex.org/I185443292"]},{"id":"https://openalex.org/I4210090317","display_name":"The Barbara Ann Karmanos Cancer Institute","ror":"https://ror.org/00ee40h97","country_code":"US","type":"facility","lineage":["https://openalex.org/I2800590384","https://openalex.org/I4210090317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jing Li","raw_affiliation_strings":["Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit,","institution_ids":["https://openalex.org/I185443292","https://openalex.org/I4210090317"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2615,"currency":"USD","value_usd":2615},"apc_paid":{"value":2615,"currency":"USD","value_usd":2615},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.47428731,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"8","issue":"Supplement_6","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10958","display_name":"Ultrasound and Hyperthermia Applications","score":0.961899995803833,"subfield":{"id":"https://openalex.org/subfields/2204","display_name":"Biomedical Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10958","display_name":"Ultrasound and Hyperthermia Applications","score":0.961899995803833,"subfield":{"id":"https://openalex.org/subfields/2204","display_name":"Biomedical Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11872","display_name":"Barrier Structure and Function Studies","score":0.028200000524520874,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.0034000000450760126,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/focused-ultrasound","display_name":"focused ultrasound","score":0.9900000095367432},{"id":"https://openalex.org/keywords/blood-brain-barrier-disruption","display_name":"blood-brain barrier disruption","score":0.7870000004768372},{"id":"https://openalex.org/keywords/microbubbles","display_name":"microbubbles","score":0.7350000143051147},{"id":"https://openalex.org/keywords/brain-tumor-drug-delivery","display_name":"brain tumor drug delivery","score":0.8730000257492065},{"id":"https://openalex.org/keywords/physiologically-based-pharmacokinetic-model","display_name":"physiologically based pharmacokinetic modeling","score":0.9480000138282776},{"id":"https://openalex.org/keywords/paracellular-permeability","display_name":"paracellular permeability","score":0.7480000257492065},{"id":"https://openalex.org/keywords/temozolomide","display_name":"temozolomide","score":0.9459999799728394},{"id":"https://openalex.org/keywords/trastuzumab","display_name":"trastuzumab","score":0.9929999709129333},{"id":"https://openalex.org/keywords/trastuzumab-emtansine","display_name":"trastuzumab emtansine","score":0.9679999947547913},{"id":"https://openalex.org/keywords/trastuzumab-deruxtecan","display_name":"trastuzumab deruxtecan","score":0.9990000128746033},{"id":"https://openalex.org/keywords/antibody-drug-conjugates","display_name":"antibody-drug conjugates","score":0.9319999814033508},{"id":"https://openalex.org/keywords/systemic-pharmacokinetics","display_name":"systemic pharmacokinetics","score":0.5899999737739563}],"concepts":[{"id":"https://openalex.org/C2778402981","wikidata":"https://www.wikidata.org/wiki/Q221694","display_name":"Blood\u2013brain barrier","level":3,"score":0.6446999907493591},{"id":"https://openalex.org/C2779820397","wikidata":"https://www.wikidata.org/wiki/Q1392806","display_name":"Drug delivery","level":2,"score":0.5909000039100647},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.5277000069618225},{"id":"https://openalex.org/C529278444","wikidata":"https://www.wikidata.org/wiki/Q47273","display_name":"Central nervous system","level":2,"score":0.5218999981880188},{"id":"https://openalex.org/C138944611","wikidata":"https://www.wikidata.org/wiki/Q1163287","display_name":"Clearance","level":2,"score":0.5085999965667725},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.49140000343322754},{"id":"https://openalex.org/C185350488","wikidata":"https://www.wikidata.org/wiki/Q615386","display_name":"Transcytosis","level":4,"score":0.4645000100135803},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4575999975204468},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.41920000314712524},{"id":"https://openalex.org/C185867374","wikidata":"https://www.wikidata.org/wiki/Q2562769","display_name":"Physiologically based pharmacokinetic modelling","level":3,"score":0.3709999918937683},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.3621000051498413},{"id":"https://openalex.org/C64012434","wikidata":"https://www.wikidata.org/wiki/Q6839290","display_name":"Microbubbles","level":3,"score":0.353300005197525},{"id":"https://openalex.org/C25938499","wikidata":"https://www.wikidata.org/wiki/Q7663812","display_name":"Systemic administration","level":3,"score":0.35100001096725464},{"id":"https://openalex.org/C2777670902","wikidata":"https://www.wikidata.org/wiki/Q492038","display_name":"Human brain","level":2,"score":0.34220001101493835},{"id":"https://openalex.org/C134728086","wikidata":"https://www.wikidata.org/wiki/Q966900","display_name":"Drug delivery to the brain","level":4,"score":0.3393999934196472},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.3325999975204468},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.3059000074863434},{"id":"https://openalex.org/C13245373","wikidata":"https://www.wikidata.org/wiki/Q3715494","display_name":"Drug carrier","level":3,"score":0.29170000553131104},{"id":"https://openalex.org/C60903277","wikidata":"https://www.wikidata.org/wiki/Q2051926","display_name":"Paracellular transport","level":4,"score":0.2897000014781952},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.28610000014305115},{"id":"https://openalex.org/C126511603","wikidata":"https://www.wikidata.org/wiki/Q1261145","display_name":"Targeted drug delivery","level":3,"score":0.2858000099658966},{"id":"https://openalex.org/C2779130545","wikidata":"https://www.wikidata.org/wiki/Q233309","display_name":"Brain tumor","level":2,"score":0.2842000126838684},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.2833000123500824},{"id":"https://openalex.org/C64903051","wikidata":"https://www.wikidata.org/wiki/Q2198549","display_name":"Drug development","level":3,"score":0.28200000524520874},{"id":"https://openalex.org/C2777807558","wikidata":"https://www.wikidata.org/wiki/Q4914764","display_name":"Biodistribution","level":3,"score":0.2685000002384186},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.2597000002861023},{"id":"https://openalex.org/C110121322","wikidata":"https://www.wikidata.org/wiki/Q865811","display_name":"Distribution (mathematics)","level":2,"score":0.25780001282691956}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1093/noajnl/vdag161.022","doi":"https://doi.org/10.1093/noajnl/vdag161.022","is_oa":true,"landing_page_url":"https://doi.org/10.1093/noajnl/vdag161.022","pdf_url":null,"source":{"id":"https://openalex.org/S4210237914","display_name":"Neuro-Oncology Advances","issn_l":"2632-2498","issn":["2632-2498"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","ki-jl-1","norway-1","poland-20","russia-white-list-4"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neuro-Oncology Advances","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13448351","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13448351/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neurooncol Adv","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1093/noajnl/vdag161.022","doi":"https://doi.org/10.1093/noajnl/vdag161.022","is_oa":true,"landing_page_url":"https://doi.org/10.1093/noajnl/vdag161.022","pdf_url":null,"source":{"id":"https://openalex.org/S4210237914","display_name":"Neuro-Oncology Advances","issn_l":"2632-2498","issn":["2632-2498"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","ki-jl-1","norway-1","poland-20","russia-white-list-4"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neuro-Oncology Advances","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9763000011444092}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.7373878955841064}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7204479122","https://openalex.org/W2889014367","https://openalex.org/W2899699879","https://openalex.org/W4396748587","https://openalex.org/W2967858621","https://openalex.org/W4386398795","https://openalex.org/W4416140893","https://openalex.org/W2912345775","https://openalex.org/W2052864664","https://openalex.org/W7097136833"],"abstract_inverted_index":{"Abstract":[0],"Focused":[1],"ultrasound":[2],"(FUS)":[3],"combined":[4],"with":[5,103,108,115,129],"systemically":[6],"administered":[7],"microbubbles":[8],"enables":[9,272],"transient":[10],"disruption":[11],"of":[12,28,34,87,257],"the":[13,88,145,245,255],"blood\u2013brain":[14],"barrier":[15],"(BBB),":[16],"offering":[17],"a":[18,51,250],"promising":[19],"strategy":[20],"to":[21,59,70,140,262,284,288],"enhance":[22],"central":[23],"nervous":[24],"system":[25],"(CNS)":[26],"delivery":[27,69,261,287],"therapeutics.":[29],"However,":[30],"limited":[31],"quantitative":[32],"understanding":[33],"how":[35],"FUS-induced":[36,109,165],"BBB":[37,110,120,131,166,178,193,203,212,236,268,278],"opening":[38,132,167,237,279],"modulates":[39],"CNS":[40,61,71,75,90,173,199,224,259],"pharmacokinetics":[41],"(PK)":[42],"hinders":[43],"its":[44],"rational":[45],"clinical":[46],"translation.":[47],"This":[48],"study":[49],"developed":[50,79],"mechanistic,":[52],"physiologically":[53],"based":[54],"pharmacokinetic":[55],"(PBPK)":[56],"modeling":[57],"framework":[58,253],"characterize":[60],"PK":[62],"and":[63,84,91,112,134,152,158,181,186,195,205,210,230,239,267,282],"identify":[64],"key":[65,82],"determinants":[66],"governing":[67],"drug":[68,240,260,263],"tumors.":[72,93],"A":[73],"9-compartment":[74],"PBPK":[76,247],"model":[77,95,137,248],"was":[78,121,138],"that":[80,164],"captured":[81],"anatomical":[83],"pathophysiological":[85],"features":[86],"human":[89],"brain":[92,289],"The":[94,136],"included":[96],"three":[97],"tumor":[98,102,107,114,174],"compartments,":[99],"representing":[100],"infiltrative":[101,106],"intact":[104],"BBB,":[105],"opening,":[111],"bulk":[113],"constitutively":[116],"disrupted":[117],"BBB.":[118],"FUS-disrupted":[119],"modeled":[122],"as":[123,222],"time-dependent":[124],"increases":[125],"in":[126],"paracellular":[127],"permeability":[128,194],"defined":[130],"onset":[133,238],"duration.":[135],"applied":[139],"four":[141],"therapeutic":[142,286],"drugs,":[143],"including":[144],"small-molecule":[146],"temozolomide,":[147,223],"HER2":[148],"monoclonal":[149],"antibody":[150],"trastuzumab,":[151],"antibody\u2013drug":[153,187],"conjugates":[154],"trastuzumab":[155,159],"emtansine":[156],"(T-DM1)":[157],"deruxtecan":[160],"(T-DXd).":[161],"Simulations":[162],"suggest":[163],"produces":[168],"distinct,":[169],"drug-specific":[170],"effects":[171],"on":[172],"PK,":[175],"driven":[176],"by":[177],"transport":[179,269],"kinetics":[180],"systemic":[182,197,228,265],"pharmacokinetics.":[183],"For":[184],"antibodies":[185],"conjugates,":[188],"which":[189,271],"exhibit":[190],"intrinsically":[191],"low":[192],"prolonged":[196],"exposure,":[198],"penetration":[200,225],"is":[201,226],"predominantly":[202],"permeability-limited":[204],"benefits":[206],"from":[207],"sufficiently":[208],"large":[209],"sustained":[211],"disruption.":[213],"In":[214,243],"contrast,":[215],"for":[216,276],"rapidly":[217],"cleared":[218],"small":[219],"molecules":[220],"such":[221],"primarily":[227],"exposure-limited":[229],"requires":[231],"precise":[232],"temporal":[233],"alignment":[234],"between":[235],"administration":[241],"time.":[242],"conclusion,":[244],"9-CNS":[246],"provides":[249],"mechanistic":[251],"computational":[252],"linking":[254],"efficiency":[256],"FUS-enhanced":[258],"properties,":[264],"pharmacokinetics,":[266],"kinetics,":[270],"tailoring":[273],"FUS":[274],"parameters":[275],"optimal":[277],"onset,":[280],"duration,":[281],"magnitude":[283],"maximize":[285],"tumors":[290],"while":[291],"maintaining":[292],"safety.":[293]},"counts_by_year":[],"updated_date":"2026-10-29T09:56:32.521200","created_date":"2026-08-08T00:00:00"}
