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. 2016 Nov 17;6:37094. doi: 10.1038/srep37094

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Copyright © 2016, The Author(s)

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(A) In order to study the intra-animal variation, NHP 1 was sonicated with the same targeting (putamen) and acoustic parameters (275 kPa) in a bi-weekly basis five times. FUS-induced BBB opening was performed in three NHPs with the opening volume (B), and the drug delivery analysis was performed in two NHPs for the amount of Gd delivered and the delivery efficiency (C). NHP 1 to NHP 3 were sonicated 7, 12, and 24 times, respectively, and the error bar represents standard deviation. Both (B) and (C) showed an inter-animal variation as the BBB opening threshold for NHP 1 and 2 were lower than that for NHP 3. Quantified cavitation doses (SCD_h: stable cavitation dose with harmonics, SCD_u: stable cavitation dose with ultraharmonics, ICD: inertial cavitation dose) were correlated with the BBB opening outcomes. The SCD_h can be used to detect the effectiveness of BBB opening (D). For a quantitative assessment, the opening volume (E), the amount of delivered Gd and delivery efficiency (F) was positively correlated with the total cavitation dose (SCD_h + SCD_u + ICD). (The R² of the linear fitting in (E) for NHP 1 to 3 and all experiments across animals was 0.81, 0.63, 0.50, and 0.47, respectively; that in (F) for NHP 2, 3, and all experiments across animals was 0.52, 0.71, and 0.61, respectively.)