Name: mri-guided disruption of the blood-brain barrier using transcranial focused ultrasound in a rat model
Uploaded: 2012-03-13T13:00:00
Description: Watch this Scientific Journal Video about MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model at JoVE.com

Forfatterne ønsker å takke Shawna Rideout-Gros og Alexandra Garces for deres hjelp med dyret omsorg, og Ping Wu for henne teknisk assistanse. Støtte for dette arbeidet ble gitt av National Institutes of Health i henhold til stipend nei. EB003268, og Canada Research Stoler Program.

1. Ultralyd og MR Setup En MR-kompatible tre akser fokusert ultralyd system ble brukt i denne studien (FUS Instruments, Inc., Toronto, Ontario, Canada). To forskjellige ultralyd transdusere ble brukt: en i-hus bygd 551,5 kHz sfærisk-fokusert svinger (krumningsradius = 60 mm, ytre diameter = 75 mm, innvendig diameter = 20 mm), og en 1,503 MHz, 8-sektoren array med integrert PZT hydrofon (Imasonic Inc., Voray-sur-L&#39;Orgnon, Frankrike) drevet som et enkelt element sfærisk fokusert transducer...

<ol>
	<li>Kinoshita, M., McDannold, N., Jolesz, F. A., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+localized+delivery+of+Herceptin+to+the+mouse+brain+by+MRI-guided+focused+ultrasound-induced+blood-brain+barrier+disruption.">Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption.</a> Proc. Natl. Acad. Sci. U.S.A. 103, 11719-11723 (2006).</li><li>Jord&#227;o, J. F., Ayala-Grosso, C. A., Markham, K., Huang, Y., Chopra, R., McLaurin, J., Hynynen, K., Aubert, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antibodies+targeted+to+the+brain+with+image-guided+focused+ultrasound+reduces+amyloid-beta+plaque+load+in+the+TgCRND8+mouse+model+of+Alzheimer&#39;s+disease.">Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer&#39;s disease.</a> PLoS One. 5 (5), e10549-e10549 (2010).</li><li>Liu, H. -. L., Hua, M. -. Y., Chen, P. -. Y., Chu, P. -. C., Pan, C. -. H., Yang, H. -. W., Huang, C. -. Y., Wang, J. -. J., Yen, T. -. C., Wei, K. -. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-brain+barrier+disruption+with+focused+ultrasound+enhances+delivery+of+chemotherapeutic+drugs+for+glioblastoma+treatment.">Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.</a> Radiology. 255, 415-425 (2010).</li><li>Hynynen, K., McDannold, N., Vykhodtseva, N., Jolesz, F. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+MR+imaging-guided+focal+opening+of+the+blood-brain+barrier+in+rabbits.">Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits.</a> Radiology. 220, 640-646 (2001).</li><li>Choi, J. J., Wang, S., Tung, Y. -. S., Morrison, B., Konofagou, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecules+of+various+pharmacologically-relevant+sizes+can+cross+the+ultrasound-induced+blood-brain+barrier+opening+in+vivo.">Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo.</a> Ultrasound Med. Biol. 36, 58-67 (2010).</li><li>Pardridge, W. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+blood-brain+barrier:+bottleneck+in+brain+drug+development.">The blood-brain barrier: bottleneck in brain drug development.</a> NeuroRx. 2, 3-14 (2005).</li><li>Bing, K. F., Howles, G. P., Qi, Y., Palmeri, M. L., Nightingale, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-brain+barrier+&#40;BBB&#41;+disruption+using+a+diagnostic+ultrasound+scanner+and+Definity+in+mice.">Blood-brain barrier &#40;BBB&#41; disruption using a diagnostic ultrasound scanner and Definity in mice.</a> Ultrasound Med. Biol. 35, 1298-1308 (2009).</li><li>O'Reilly, M. A., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+PVDF+receiver+for+ultrasound+monitoring+of+transcranial+focused+ultrasound+therapy.">A PVDF receiver for ultrasound monitoring of transcranial focused ultrasound therapy.</a> IEEE Trans. Biomed. Eng. 57, 2286-2294 (2010).</li><li>Chopra, R., Curiel, L., Staruch, R., Morrison, L., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+MRI-compatible+system+for+focused+ultrasound+experiments+in+small+animal+models.">An MRI-compatible system for focused ultrasound experiments in small animal models.</a> Med. Phys. 36, 1867-1874 (2009).</li><li>McDannold, N., Zhang, Y., Vykhodtseva, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-Brain+Barrier+Disruption+and+Vascular+Damage+Induced+by+Ultrasound+Bursts+Combined+with+Microbubbles+can+be+Influenced+by+Choice+of+Anesthesia+Protocol.">Blood-Brain Barrier Disruption and Vascular Damage Induced by Ultrasound Bursts Combined with Microbubbles can be Influenced by Choice of Anesthesia Protocol.</a> Ultrasound Med. Biol. , (2011).</li><li>McDannold, N., Vykhodtseva, N., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Targeted+disruption+of+the+blood-brain+barrier+with+focused+ultrasound:+association+with+cavitation+activity.">Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity.</a> Phys. Med. Biol. 51, 793-807 (2006).</li><li>Yang, F. -. Y., Liu, S. -. H., Ho, F. -. M., Chang, C. -. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+ultrasound+contrast+agent+dose+on+the+duration+of+focused-ultrasound-induced+blood-brain+barrier+disruption.">Effect of ultrasound contrast agent dose on the duration of focused-ultrasound-induced blood-brain barrier disruption.</a> J. Acoust. Soc. Am. 126, 3344-3349 (2009).</li><li>McDannold, N., Vykhodtseva, N., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-brain+barrier+disruption+induced+by+focused+ultrasound+and+circulating+preformed+microbubbles+appears+to+be+characterized+by+the+mechanical+index.">Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index.</a> Ultrasound Med. Biol. 34, 834-840 (2008).</li><li>Neppiras, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acoustic+Cavitation.">Acoustic Cavitation.</a> Physics Reports (Review Section of Physics Letters). 61, 159-251 (1980).</li><li>O&#39;Reilly, M. A., Huang, Y., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+standing+wave+effects+on+transcranial+focused+ultrasound+disruption+of+the+blood-brain+barrier+in+a+rat+model.">The impact of standing wave effects on transcranial focused ultrasound disruption of the blood-brain barrier in a rat model.</a> Phys. Med. Biol. 55, 5251-5267 (2010).</li></ol>

Forberedelse av dyrene og mikrobobler er de mest kritiske aspekter ved denne prosedyren. Pelsen på dyrets hode må helt fjernet for å unngå demping ultralydstrålen. BBB kan bli avbrutt etter isofluorane bedøvelse, men blir det vanskeligere å oppnå konsistent åpning. Mikrobobler skal alltid behandles med forsiktighet og liten måler, må med stor diameter nåler brukes ved utarbeiding, for å unngå å bryte dem. Likeledes bør den minste måleren kateteret som med rimelighet kan bruk...

<table border="1"><tbody><tr><td> Navn på reagensen </td><td> Firma </td><td> Katalognummer </td></tr><tr><td> Small Animal fokusert ultralyd System </td><td> FUS Instruments, Inc. </td><td> RK-100 </td></tr><tr><td> Definity </td><td> Lantheus bildediagnostikk </td><td></td></tr><tr><td> Omniscan </td><td> GE Healthcare </td><td></td></tr></tbody></table>

mri-guided disruption of the blood-brain barrier using transcranial focused ultrasound in a rat model

Fokusert ultralyd (FUS) forstyrrelse av blod-hjerne barrieren (BBB) ​​er en stadig etterforsket teknikk for å omgå BBB 1-5. BBB er et betydelig hinder for farmasøytiske behandlinger av hjernen lidelser som det begrenser passasje av molekyler fra blodkar i hjernen vev til molekyler mindre enn ca 500 DA i størrelse 6. FUS indusert BBB avbrudd (BBBD) er midlertidig og reversibel 4 og har en fordel over kjemiske midler for å indusere BBBD ved å være svært lokalisert. FUS indusert BBBD gir et middel for å undersøke virkningene av et bredt spekter av terapeutiske agenter på hjernen, noe som ellers ikke ville være leveransen til vevet i tilstrekkelig konsentrasjon. Mens et bredt spekter av ultralyd parametere har vist seg vellykket på å forstyrre BBB 2,5,7, er det flere kritiske trinn i den eksperimentelle prosedyren for å sikre en vellykket avbrudd med nøyaktig målretting. Dette protocol skisserer hvordan å oppnå MRI-guidede FUS indusert BBBD i en rotte modell, med fokus på kritiske dyret forberedelse og mikrobobleutskillere håndtering trinn i eksperimentet.

Watch this Scientific Journal Video about MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model at JoVE.com

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

Mikrobobleutskillere-mediert fokusert ultralyd forstyrrelse av blod-hjerne barrieren (BBB) ​​er en lovende teknikk for ikke-invasiv målrettet levering av legemidler i hjernen<sup&gt; 1-3</sup&gt;. Denne protokollen beskriver det eksperimentelle prosedyre for MR-veiledet transkranial BBB avbrudd i en rotte modell.

MR-veiledet Forstyrrelse av blod-hjerne-barrieren ved hjelp Transkraniell fokusert ultralyd i en rotte Model

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

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Blood-brain barrier (BBB) coverage plays a central role in the homeostasis of the central nervous system (CNS). The BBB is dynamically maintained by ...