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. 2013 Jan;34(1):115-20.
doi: 10.3174/ajnr.A3150. Epub 2012 Jun 21.

Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine

K-C Wei  1 , 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
Affiliations

Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine

K-C Wei et al. AJNR Am J Neuroradiol. 2013 Jan.

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 (r(2) = 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.

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Figures

Fig 1.
Fig 1.
Typical MR image sets (0.43-MPa pressure). Column 1: T1-weighted images obtained in the first MR imaging scan (before FUS exposure, for neuronavigation guidance). Columns 2–4: T1, CE-T1, and subtracted T1-weighted images obtained in the second MR imaging scan (after FUS exposure, for treatment validation). Column 5: T2-weighted images. Column 6: Susceptibility-weighted images. Zoomed regions (right) demonstrate the measured discrepancy between the targeted and maximum SI increase locations at targets 1 and 2 (0.7 and 1.5 mm, respectively).
Fig 2.
Fig 2.
R1 maps and the Evans blue–stained brain sections obtained from single-point (A, B; same animal as Fig 1) and multipoint (3 × 3) FUS exposures (C, D). Arrows denote significant R1 (A, B) or Gd-DTPA leakage regions (C, D). Size bar = 10 mm.
Fig 3.
Fig 3.
A, Discrepancy (in mm) between the planned target point and BBB-opening points measured from subtracted CE-T1-weighted images of all experiments. The average discrepancy was 2.3 ± 0.9 mm. B, MR imaging signal intensity increase obtained from the signal differences between T1- and CE-T1-weighted images at the sonication target after different FUS exposure levels (0.26, 0.43, and 0.56 MPa). C, The difference (in seconds−1) between R1 measurements of the first and the second (postoperative) MR imaging scans under different FUS pressures (0.26, 0.43, and 0.56 MPa). D, Correlation between the measured Gd concentration (in mM; from ICP-OES assay; gray marker) and the SI contrast enhancement (in %) obtained from T1 images, and correlation between the measured Gd concentration (in mM) from ICP-OES assay and the estimated Gd concentration (in mM) from MR imaging R1 maps (black markers).
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