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Research ArticleBrain
Open Access

Neuronavigation-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening: A Preliminary Study in Swine

K.-C. Wei, H.-C. Tsai, Y.-J. Lu, H.-W. Yang, M.-Y. Hua, M.-F. Wu, P.-Y. Chen, C.-Y. Huang, T.-C. Yen and H.-L. Liu
American Journal of Neuroradiology January 2013, 34 (1) 115-120; DOI: https://doi.org/10.3174/ajnr.A3150
K.-C. Wei
aFrom the Departments of Neurosurgery (K.-C.W., H.-C.T., Y.-J.L., P.-Y.C., C.-Y.H.)
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H.-C. Tsai
aFrom the Departments of Neurosurgery (K.-C.W., H.-C.T., Y.-J.L., P.-Y.C., C.-Y.H.)
gGraduate Institute of Clinical Medical Sciences (H.-C.T.), Chang-Gung University and Memorial Hospital, Taoyuan, Taiwan
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Y.-J. Lu
aFrom the Departments of Neurosurgery (K.-C.W., H.-C.T., Y.-J.L., P.-Y.C., C.-Y.H.)
cChemical and Material Engineering (Y.-J.L., H.-W.Y., M.-Y.H., P.-Y.C.)
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H.-W. Yang
cChemical and Material Engineering (Y.-J.L., H.-W.Y., M.-Y.H., P.-Y.C.)
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M.-Y. Hua
cChemical and Material Engineering (Y.-J.L., H.-W.Y., M.-Y.H., P.-Y.C.)
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M.-F. Wu
hAnimal Medicine Center (M.-F.W.), National Taiwan University, Taipei, Taiwan.
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P.-Y. Chen
aFrom the Departments of Neurosurgery (K.-C.W., H.-C.T., Y.-J.L., P.-Y.C., C.-Y.H.)
cChemical and Material Engineering (Y.-J.L., H.-W.Y., M.-Y.H., P.-Y.C.)
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C.-Y. Huang
aFrom the Departments of Neurosurgery (K.-C.W., H.-C.T., Y.-J.L., P.-Y.C., C.-Y.H.)
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T.-C. Yen
bNuclear Medicine (T.-C.Y.)
eMolecular Imaging Center (T.-C.Y., H.-L.L.)
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H.-L. Liu
dElectrical Engineering (H.-L.L.)
eMolecular Imaging Center (T.-C.Y., H.-L.L.)
fHealthy Aging Research Center (H.-L.L.)
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Abstract

BACKGROUND AND PURPOSE: FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure and investigate its feasibility in vivo in large animals.

MATERIALS AND METHODS: We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 swine by more than 40 sonication procedures and evaluated by MR imaging. Gd-DTPA concentration was quantitated in vivo by MR imaging R1 relaxometry and compared with ICP-OES assay. Brain histology after FUS exposure was investigated using H&E and TUNEL staining.

RESULTS: Neuronavigation could successfully guide the focal beam, with precision comparable to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). A FUS pressure of 0.43 MPa resulted in consistent BBB opening. Neuronavigation-guided BBB opening increased Gd-DTPA deposition by up to 1.83 mmol/L (a 140% increase). MR relaxometry demonstrated high correlation with ICP-OES measurements (r2 = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging.

CONCLUSIONS: Neuronavigation provides sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain can be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.

ABBREVIATIONS:

CE
contrast-enhanced
FUS
focused sonography
Gd-DTPA
gadolinium-diethylene-triamine pentaacetic acid
ICP-OES
inductively coupled plasma optical emission spectroscopy
MRgFUS
MR-guided FUS
SI
signal intensity
TUNEL
terminal deoxynucleotidyl transferase biotin-dUTP nick end-labeling
  • © 2013 by American Journal of Neuroradiology

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American Journal of Neuroradiology: 34 (1)
American Journal of Neuroradiology
Vol. 34, Issue 1
1 Jan 2013
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Neuronavigation-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening: A Preliminary Study in Swine
K.-C. Wei, H.-C. Tsai, Y.-J. Lu, H.-W. Yang, M.-Y. Hua, M.-F. Wu, P.-Y. Chen, C.-Y. Huang, T.-C. Yen, H.-L. Liu
American Journal of Neuroradiology Jan 2013, 34 (1) 115-120; DOI: 10.3174/ajnr.A3150

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Neuronavigation-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening: A Preliminary Study in Swine
K.-C. Wei, H.-C. Tsai, Y.-J. Lu, H.-W. Yang, M.-Y. Hua, M.-F. Wu, P.-Y. Chen, C.-Y. Huang, T.-C. Yen, H.-L. Liu
American Journal of Neuroradiology Jan 2013, 34 (1) 115-120; DOI: 10.3174/ajnr.A3150
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