Fig. 6: Passive cavitation detector response shows no signature of BBB opening in vivo. | Nature Communications

Fig. 6: Passive cavitation detector response shows no signature of BBB opening in vivo.

From: Non-invasive molecularly-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and uncaging of drug carriers

Fig. 6

a Fast Fourier Transform (FFT) analysis of representative responses to standard4-FUS sequence. Broadband emissions (shaded box) and ultra-harmonics (3.75 and 6.25 MHz) are detected only in the presence of UC-carriers (red) as compared to saline (black), indicating the inertial cavitation regime of BBB opening (see Supplementary Fig. 12). b FFT analysis of representative response to standard3-FUS sequence. Ultra-harmonics but not broadband emissions (signatures of stable cavitation46) are detected only in the presence of UC-carriers (red) as compared to saline (black), consistent with stable-cavitation regime of BBB opening (see Supplementary Fig. 12). Insets show ultra-harmonics and integer harmonics. Data is mean of 50 pulses (a, b). c FFT analysis of representative response to AU-FUS uncaging sequence (preceded by AU-FUS aggregation sequence) showing neither ultra-harmonics nor broadband emissions in the presence of UC-carriers (red) vs. saline (black), consistent with no BBB opening (see Supplementary Fig. 12). Insets show integer harmonics. Note that the FFT data has less samples due to 0.4 ms pulse width vs 2 ms in others. d FFT analysis of representative response to AU-FUS aggregation sequence (preceding the AU-FUS uncaging sequence) showing neither ultra-harmonics nor broadband emissions in the presence of UC-carriers (red) vs. saline (black), suggesting no BBB opening (see Supplementary Fig. 12). Insets indicates integer harmonics. Data is mean of 7 pulses (c, d). e Calculation of ultra-harmonics above baseline [n = 150 (3 rats × 50 pulses) for standard3,4-FUS, n = 21 (3 rats × 7 pulses) for AU-FUS sequence]. All data is mean ± s.e.m. One-tailed, unpaired t-test with Welch’s correction, aggregate seq. vs. standard3-FUS, **p = 0.0052; uncage seq. vs. standard3-FUS, **p = 0.0026; aggregate seq. vs. standard4-FUS, ****p < 0.0001; uncage seq. vs. standard4-FUS, ****p < 0.0001; standard3-FUS vs. standard4-FUS, ****p < 0.0001. f Calculation of broadband emissions above baseline [n = 150 (3 rats × 50 pulses) for standard3,4-FUS, n = 21 (3 rats × 7 pulses) for AU-FUS sequence]. All data is mean ± s.e.m. One-tailed, unpaired t-test with Welch’s correction, aggregate seq. vs. standard4-FUS, ****p < 0.0001; uncage seq. vs. standard4-FUS, ****p < 0.0001; standard3-FUS vs. standard4-FUS, ****p < 0.0001. Pressures account for skull attenuation (see Table 1). See Supplementary Fig. 11 for PCD setup.

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