title: Evaluation of the increase in permeability of the blood-brain barrier during tumor progression after pulsed focused ultrasound.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the permeability of the blood-brain barrier after sonication by pulsed high-intensity focused ultrasound and to determine if such an approach increases the tumor:ipsilateral brain permeability ratio.
  
  
  METHODS
  F98 glioma-bearing Fischer 344 rats were injected intravenously with Evans blue with or without blood-tumor barrier disruption induced by transcranial pulsed high-intensity focused ultrasound. Sonication was applied at a frequency of 1 MHz with a 5% duty cycle and a repetition frequency of 1 Hz. The permeability of the blood-brain barrier was assessed by the extravasation of Evans blue. Contrast-enhanced magnetic resonance images were used to monitor the gadolinium deposition path associated with transcranial pulsed high-intensity focused ultrasound, and the influencing size and location was also investigated. In addition, whole brain histological analysis was performed. The results were compared by two-tailed unpaired t-test.
  
  
  RESULTS
  The accumulation of Evans blue in brains and the tumor:ipsilateral brain permeability ratio of Evans blue were significantly increased after pulsed high-intensity focused ultrasound exposure. Evans blue injection followed by sonication showed an increase in the tumor:ipsilateral brain ratio of the target tumors (9.14:1) of about 2.23-fold compared with the control tumors (x4.09) on day 6 after tumor implantation. Magnetic resonance images showed that pulsed high-intensity focused ultrasound locally enhances the permeability of the blood-tumor barrier in the glioma-bearing rats.
  
  
  CONCLUSIONS
  This method could allow enhanced synergistic effects with respect to other brain tumor treatment regimens.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan. fyyang@ym.edu.tw
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.forename: Guan-Liang
authors.initials: GL
authors.lastname: Lin
authors.forename: Hui-Hsien
authors.initials: HH
authors.lastname: Lin
authors.forename: Tai-Tong
authors.initials: TT
authors.lastname: Wong
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000528:radiation effects; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000528:radiation effects*; D018450:Disease Progression; D005070:Evans Blue / Q000378:metabolism; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D014463:Ultrasonography / Q000379:methods
chemical_list: D005070:Evans Blue