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

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  Online Figure 1: A, Experimental setup showing the neuronavigation system registration of the focal point position of the FUS transducer on the neuronavigation system. M1/M2 indicate markers providing spatial reference for the neuronavigation system; T indicates FUS transducer. B, Images from the neuronavigation screens showing interactive positional changes of the FUS focal beam (red) to the planned target position (yellow. C and D, Free-field measured and transcranially measured pressure distributions of the applied FUS along the transducer's axis (left) and along the cross-sectional direction (right). The pressure decay (calculated as the fractional loss of pressure measured before and after skull insertion) was found to be approximately 30% after FUS energy penetrated through the swine skull; however, no focal beam shift was observed along the cross-sectional direction.
  
  Online Figure 2: MR in vitro relaxometry of Gd-DTPA for imaging-concentration correlation. A, T1-weighted images of the samples; R1 mapping of the samples (B); relationship of longitudinal relaxation (R1, in seconds 1) versus Gd-DTPA concentration (in mM) (C). Linear fit was obtained between the gadolinium ion concentration and R1. A R1 relaxivity of 3.821 was estimated. Gd-DTPA concentration in numbered wells in panelA: (1): 0 mmol/L (2); 0.24 mmol/L (3); 0.49 mmol/L (4); 0.97 mmol/L (5); 1.96 mmol/L (6); 3.9 mmol/L (7); 7.8 mmol/L (8); 15 mmol/L. The other wells of the cell-culture dish were filled with degassed water.
  
  Online Figure 3: H&E-stained (upper panel) and TUNEL-stained (lower panel) brain sections characterized as different hemorrhagic damage levels. A, grade 0: no damage; grade I: no damage but with temporal vasodilatations (B); grade II: small groupings of erythrocyte extravasations (C); grade III: extensive erythrocyte extravasations or perivascular hemorrhages (D). Bar 100 μm.
  
  Online Table 1: Summary of animal experiments
  
  Online Table 2: Summary of histologic examination