{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:44:04Z","timestamp":1792039444966,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["GTL25071\u2010000"],"award-info":[{"award-number":["GTL25071\u2010000"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102026\u201025481820"],"award-info":[{"award-number":["RS\u20102026\u201025481820"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Ultrasound Medicine"],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine whether minute\u2010scale microbubble handling and injection\u2010to\u2010sonication timing are associated with vessel\u2010level focused ultrasound (FUS)\u2013mediated blood\u2013brain barrier opening (BBBO), and whether control normalization improves longitudinal 2\u2010photon (2P) measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cranial\u2010windowed mice received FITC\u2013dextran (40\u2009kDa) and SonoVue microbubbles by retro\u2010orbital injection, followed by 1.0\u2009MHz FUS at 0.2\u20130.4\u2009MPa. Two\u2010photon stacks were acquired over 0\u201315\u2009minutes. Frangi vesselness and Otsu thresholding defined vessel masks and a perivascular ring for extravasation analysis. Three timing conditions were compared: standard (injection within ~5\u2009seconds of reconstitution, sonication immediately); Microbubble Floating (microbubbles held 2\u2009minutes before injection); and Sonication Delay (sonication started 2\u2009minutes after injection). Per\u2010mouse AUC used 2\u2010way ANOVA; slice\u2010level vessel\u2010area dependence used a linear mixed\u2010effects model with mouse as a random intercept.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Control intravascular fluorescence decreased by ~24% over 15\u2009minutes, showing that the intravascular signal is not a stable denominator; control\u2010normalized extravascular AUC was therefore the primary metric. Under the standard protocol, extravascular AUC peaked at 0.3\u2009MPa, but the across\u2010pressure difference was not significant (\n                      <jats:italic>F<\/jats:italic>\n                      (2,6)\u2009=\u20093.36,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.105). Timing effects were descriptive: relative to standard, both Microbubble Floating and Sonication Delay increased extravascular AUC at 0.2\u2009MPa but decreased it at 0.3\u2009MPa. Vessel area was inversely associated with extravasation at the slice level (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.37 per \u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.010), with mouse\u2010level intraclass correlation (ICC\u2009=\u20090.80) indicating dominant between\u2010mouse variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Microbubble handling and injection\u2010to\u2010sonication timing are potential protocol variables in FUS\u2010BBBO studies. Control\u2010normalized extravascular metrics provide a reproducible framework for vessel\u2010level longitudinal 2\u2010photon quantification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jum.70511","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:45:23Z","timestamp":1792035923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbubble Timing and Vascular Geometry Are Associated With Vessel\u2010Level Blood\u2013Brain Barrier Opening During Focused Ultrasound"],"prefix":"10.1002","author":[{"given":"Seongdong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyemin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Graduate School Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0665-190X","authenticated-orcid":false,"given":"Seunghwan","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Device Gachon University College of IT Convergence  Seongnam Republic of Korea"},{"name":"Clinical Technology Division Neumous Inc.  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2649-6652","authenticated-orcid":false,"given":"Sun Kwang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Graduate School Kyung Hee University  Seoul Republic of Korea"},{"name":"Department of Physiology, College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8387-9476","authenticated-orcid":false,"given":"Kisoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Kyung Hee University  Seoul Republic of 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