In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine

Hao Li Liu, Pin Yuan Chen, Hung Wei Yang, Jia Shin Wu, I. Chou Tseng, Yan Jung Ma, Chih Ying Huang, Hong Chieh Tsai, Shu Mei Chen, Yu Jen Lu, Chiung Yin Huang, Mu Yi Hua, Yunn Hwa Ma, Tzu Chen Yen, Kuo Chen Wei

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose: 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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1313-1324
Number of pages12
JournalJournal of Magnetic Resonance Imaging
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 1 2011
Externally publishedYes

Keywords

  • blood-brain barrier
  • low-frequency ultrasound
  • MRI
  • SPIO
  • swine

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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  • Cite this

    Liu, H. L., Chen, P. Y., Yang, H. W., Wu, J. S., Tseng, I. C., Ma, Y. J., Huang, C. Y., Tsai, H. C., Chen, S. M., Lu, Y. J., Huang, C. Y., Hua, M. Y., Ma, Y. H., Yen, T. C., & Wei, K. C. (2011). In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine. Journal of Magnetic Resonance Imaging, 34(6), 1313-1324. https://doi.org/10.1002/jmri.22697