High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo
High-intensity focused ultrasound (HIFU) has been shown to generate lesions that destroy brain tissue while disrupting the blood-brain barrier (BBB) in the periphery of the lesion. BBB opening, however, has not been shown without damage, and the mechanisms by which HIFU induces BBB disruption remain...
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| Veröffentlicht in: | Ultrasound in medicine & biology 2002-03, Vol.28 (3), p.389-400 |
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| container_title | Ultrasound in medicine & biology |
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| creator | Mesiwala, Ali H Farrell, Lindi Wenzel, H.Jurgen Silbergeld, Daniel L Crum, Lawrence A Winn, H.Richard Mourad, Pierre D |
| description | High-intensity focused ultrasound (HIFU) has been shown to generate lesions that destroy brain tissue while disrupting the blood-brain barrier (BBB) in the periphery of the lesion. BBB opening, however, has not been shown without damage, and the mechanisms by which HIFU induces BBB disruption remain unknown. We show that HIFU is capable of reversible, nondestructive, BBB disruption in a targeted region-of-interest (ROI) (29 of 55 applications; 26 of 55 applications showed no effect); this opening reverses after 72 h. Light microscopy demonstrates that HIFU either entirely preserves brain architecture while opening the BBB (18 of 29 applications), or generates tissue damage in a small volume within the region of BBB opening (11 of 29 applications). Electron microscopy supports these observations and suggests that HIFU disrupts the BBB by opening capillary endothelial cell tight junctions, an isolated ultrastructural effect that is different from the mechanisms through which other (untargeted) modalities, such as hyperosmotic solutions, hyperthermia and percussive injury disrupt the BBB. (E-mail: pierre@apl.washington.edu) |
| doi_str_mv | 10.1016/S0301-5629(01)00521-X |
| format | Article |
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BBB opening, however, has not been shown without damage, and the mechanisms by which HIFU induces BBB disruption remain unknown. We show that HIFU is capable of reversible, nondestructive, BBB disruption in a targeted region-of-interest (ROI) (29 of 55 applications; 26 of 55 applications showed no effect); this opening reverses after 72 h. Light microscopy demonstrates that HIFU either entirely preserves brain architecture while opening the BBB (18 of 29 applications), or generates tissue damage in a small volume within the region of BBB opening (11 of 29 applications). Electron microscopy supports these observations and suggests that HIFU disrupts the BBB by opening capillary endothelial cell tight junctions, an isolated ultrastructural effect that is different from the mechanisms through which other (untargeted) modalities, such as hyperosmotic solutions, hyperthermia and percussive injury disrupt the BBB. 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BBB opening, however, has not been shown without damage, and the mechanisms by which HIFU induces BBB disruption remain unknown. We show that HIFU is capable of reversible, nondestructive, BBB disruption in a targeted region-of-interest (ROI) (29 of 55 applications; 26 of 55 applications showed no effect); this opening reverses after 72 h. Light microscopy demonstrates that HIFU either entirely preserves brain architecture while opening the BBB (18 of 29 applications), or generates tissue damage in a small volume within the region of BBB opening (11 of 29 applications). Electron microscopy supports these observations and suggests that HIFU disrupts the BBB by opening capillary endothelial cell tight junctions, an isolated ultrastructural effect that is different from the mechanisms through which other (untargeted) modalities, such as hyperosmotic solutions, hyperthermia and percussive injury disrupt the BBB. (E-mail: pierre@apl.washington.edu)</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - physiology</subject><subject>Brain - pathology</subject><subject>Brain - ultrastructure</subject><subject>Brain Injuries - diagnostic imaging</subject><subject>Brain Injuries - etiology</subject><subject>HIFU</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Medical sciences</subject><subject>Microscopy, Electron</subject><subject>Microscopy, Polarization</subject><subject>Miscellaneous. Technology</subject><subject>Permeability</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Space life sciences</subject><subject>Tight junctions</subject><subject>Ultrasonic investigative techniques</subject><subject>Ultrasonography</subject><subject>Ultrasound</subject><issn>0301-5629</issn><issn>1879-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1P3DAQQK2qqGyhP6FVLq3oIeCxYyc5oQrRgoTEAVrtzXLsSXGVjbeeZKX99xh2BUdOM4c3X28Y-wz8FDjoszsuOZRKi_aEw3fOlYBy-Y4toKnbUrSwfM8WL8gh-0j0j3Nea1l_YIcAbd1Ugi_Yn6vw96EM44QjhWlb9NHNhL6YhylZivPoC8IB3RQ2OGwLHyjN64mK6QGLbojRl12yYSw6m1LAVOR0EzbxmB30diD8tI9H7PfPy_uLq_Lm9tf1xY-b0qmKTyVI7bVFCU0rFLqmVQ2CBV_p3qPuq3yVQw2yswKEan0FrW_6zjtAXlvB5RH7tuu7TvH_jDSZVSCHw2BHjDOZGrRUWso3QWhUwxVXGVQ70KVIlLA36xRWNm0NcPNk3jybN09aTY7P5s0y133ZD5i7FfrXqr3qDHzdA5acHfpkRxfolZMaBEiRufMdh9nbJjs15AKODn1I-Q_Gx_DGKo-PV6DW</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>Mesiwala, Ali H</creator><creator>Farrell, Lindi</creator><creator>Wenzel, H.Jurgen</creator><creator>Silbergeld, Daniel L</creator><creator>Crum, Lawrence A</creator><creator>Winn, H.Richard</creator><creator>Mourad, Pierre D</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20020301</creationdate><title>High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo</title><author>Mesiwala, Ali H ; Farrell, Lindi ; Wenzel, H.Jurgen ; Silbergeld, Daniel L ; Crum, Lawrence A ; Winn, H.Richard ; Mourad, Pierre D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-136d6ae318925ec8958e1a1d46fde6f4052ce613ba21259d419d8fbdc1e07a203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - physiology</topic><topic>Brain - pathology</topic><topic>Brain - ultrastructure</topic><topic>Brain Injuries - diagnostic imaging</topic><topic>Brain Injuries - etiology</topic><topic>HIFU</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Medical sciences</topic><topic>Microscopy, Electron</topic><topic>Microscopy, Polarization</topic><topic>Miscellaneous. Technology</topic><topic>Permeability</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Space life sciences</topic><topic>Tight junctions</topic><topic>Ultrasonic investigative techniques</topic><topic>Ultrasonography</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mesiwala, Ali H</creatorcontrib><creatorcontrib>Farrell, Lindi</creatorcontrib><creatorcontrib>Wenzel, H.Jurgen</creatorcontrib><creatorcontrib>Silbergeld, Daniel L</creatorcontrib><creatorcontrib>Crum, Lawrence A</creatorcontrib><creatorcontrib>Winn, H.Richard</creatorcontrib><creatorcontrib>Mourad, Pierre D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Ultrasound in medicine & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mesiwala, Ali H</au><au>Farrell, Lindi</au><au>Wenzel, H.Jurgen</au><au>Silbergeld, Daniel L</au><au>Crum, Lawrence A</au><au>Winn, H.Richard</au><au>Mourad, Pierre D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo</atitle><jtitle>Ultrasound in medicine & biology</jtitle><addtitle>Ultrasound Med Biol</addtitle><date>2002-03-01</date><risdate>2002</risdate><volume>28</volume><issue>3</issue><spage>389</spage><epage>400</epage><pages>389-400</pages><issn>0301-5629</issn><eissn>1879-291X</eissn><coden>USMBA3</coden><abstract>High-intensity focused ultrasound (HIFU) has been shown to generate lesions that destroy brain tissue while disrupting the blood-brain barrier (BBB) in the periphery of the lesion. BBB opening, however, has not been shown without damage, and the mechanisms by which HIFU induces BBB disruption remain unknown. We show that HIFU is capable of reversible, nondestructive, BBB disruption in a targeted region-of-interest (ROI) (29 of 55 applications; 26 of 55 applications showed no effect); this opening reverses after 72 h. Light microscopy demonstrates that HIFU either entirely preserves brain architecture while opening the BBB (18 of 29 applications), or generates tissue damage in a small volume within the region of BBB opening (11 of 29 applications). Electron microscopy supports these observations and suggests that HIFU disrupts the BBB by opening capillary endothelial cell tight junctions, an isolated ultrastructural effect that is different from the mechanisms through which other (untargeted) modalities, such as hyperosmotic solutions, hyperthermia and percussive injury disrupt the BBB. 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| subjects | Animals Biological and medical sciences Blood-brain barrier Blood-Brain Barrier - physiology Brain - pathology Brain - ultrastructure Brain Injuries - diagnostic imaging Brain Injuries - etiology HIFU Investigative techniques, diagnostic techniques (general aspects) Medical sciences Microscopy, Electron Microscopy, Polarization Miscellaneous. Technology Permeability Rats Rats, Wistar Space life sciences Tight junctions Ultrasonic investigative techniques Ultrasonography Ultrasound |
| title | High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo |
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