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. Author manuscript; available in PMC: 2013 Jul 15.
Published in final edited form as: Cancer Res. 2012 May 2;72(14):3652–3663. doi: 10.1158/0008-5472.CAN-12-0128

Fig. 1.

Fig. 1

(A): Estimation of the thresholds for BBB disruption and tissue damage in gray matter targets, as reflected in enhancement in contrast-enhanced T1-weighted imaging and hypointense spots in T2*-weighted imaging, respectively. The individual data points show measured occurrences at the different exposure levels tested, which ranged from 100–700 kPa (acoustic power: 0.2–10 W). Solid lines show logistic regression of the data (dotted lines: 95% confidence intervals). A narrow window for BBB disruption without production of MRI-evident petechaie was found. (B–D) Acoustic emission measured during sonications at locations where MRI contrast enhancement was not observed (B), was observed (C), and was accompanied by small dark spots in T2*-weighted imaging, presumably from petechaie (D). Each location was sonicated twice, once without the microbubble USCA, and once with microbubbles. Without microbubbles, only small spectral peaks were observed at the second and third harmonics of the TcMRgFUS device. With microbubbles, sonicated locations where MRI contrast extravasation was observed showed a marked increase in this harmonic activity. The third harmonic signal magnitude was enhanced by 22 and 28 times on average with microbubbles for the examples shown in (B) and (C), respectively; no enhancement was observed after the sonication shown in (A). When dark spots were seen in T2*-weighted imaging, additional emission was observed in the sensitive region of our detector (approximately 650 kHz, identified with an asterix), indicating that wideband emission – a signature of inertial cavitation – had occurred. Subharmonic and ultraharmonic emission (at 1/2, 3/2, and 5/2 of the TcMRgFUS frequency) was also observed in this example. The top and middle examples were in white matter and cortex targets, respectively, from one of the volumetric sonications shown in Fig. 4 (223 kPa). The bottom example was from a location in a volumetric sonication at 193 kPa in the visual cortex in monkey 5. The average of 20 spectra is shown in each case.