title: In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine.
abstract: OBJECTIVE
  To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions.
  
  
  METHODS
  Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping.
  
  
  RESULTS
  Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage ∼3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days.
  
  
  CONCLUSIONS
  This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.
authors.affiliation: Department of Electrical Engineering, Chang-Gung University, Taoyuan, Taiwan; Molecular Imaging Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Jia-Shin
authors.initials: JS
authors.lastname: Wu
authors.forename: I-Chou
authors.initials: IC
authors.lastname: Tseng
authors.forename: Yan-Jung
authors.initials: YJ
authors.lastname: Ma
authors.forename: Chih-Ying
authors.initials: CY
authors.lastname: Huang
authors.forename: Hong-Chieh
authors.initials: HC
authors.lastname: Tsai
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Lu
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Mu-Yi
authors.initials: MY
authors.lastname: Hua
authors.forename: Yunn-Hwa
authors.initials: YH
authors.lastname: Ma
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001923:Brain Chemistry; D003287:Contrast Media / Q000032:analysis*; D003399:Craniotomy; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000032:analysis*; D008297:Male; D053758:Nanoparticles; D013010:Sonication / Q000379:methods*; D013552:Swine
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles