NDLI: Monitoring of focused ultrasound-induced blood-brain barrier opening in non-human primates using transcranial cavitation detection in vivo and the primate skull effect

Content Provider	IEEE Xplore Digital Library
Author	Shih-Ying Wu Downs, M. Sanchez, C.S. Teichert, T. Buch, A. Samiotaki, G. Marquet, F. Yao-Sheng Tung Chen, C. Ferrera, V. Konofagou, E.
Copyright Year	2013
Description	Author affiliation: Neurosci., Columbia Univ., New York, NY, USA (Teichert, T.; Ferrera, V.) \|\| Dept. of Biomed. Eng., Columbia Univ., New York, NY, USA (Shih-Ying Wu; Downs, M.; Sanchez, C.S.; Buch, A.; Samiotaki, G.; Marquet, F.; Yao-Sheng Tung; Chen, C.; Konofagou, E.)
Abstract	Focused ultrasound (FUS) with microbubbles (MB) is promising for assisting the delivery of drugs across the blood-brain barrier (BBB). To assess the safety and efficacy, the monitoring using passive cavitation detection (PCD) is critical and yet the reliability of transcranial detection in large animals remained questioned. To study the primate skull effect, the PCD through the in-vitro monkey and human skulls and in the in vivo monkeys during the sonication (FUS frequency: 500 kHz) were investigated, with the use of in-house made lipid-shelled, monodisperse MB (median diameter: 4-5 μm) and a flatband hydrophone served as a passive cavitation detector. In the in vitro experiments, the MB were injected to the channel of the phantom under a degassed skull for sonication (peak negative pressure/PNP: 50-450 kPa, pulse length/PL: 0.2 ms, PRF: 10 Hz, duration: 2 s). A diagnostic B-mode imaging system was also used to monitor the cavitation. In the in vivo study, the PCD was realtime monitored during the sonication for PCD calibration (PNP: 50-700 kPa, PL: 0.2 ms and 10 ms, PRF: 2 Hz, duration: 10 s) and BBB opening (PNP: 200-600 kPa, PL: 10 ms, PRF: 2 Hz, duration: 2 min). The stable cavitation dose using harmonics $(SCD_{h})$ and ultraharmonics $(SCD_{u})$ and the inertial cavitation dose (ICD) were quantified. Results showed that the $SCD_{h},$ $SCD_{u},$ and ICD were detectable in vitro at 50 kPa and above, and the B-mode imaging showed bubble collapse at 200 kPa and above. The detection thresholds increased with the skulls in place, with the signal reduction of 15.4 dB for the monkey skull and 34.1 dB for the human skull. In the in vivo experiments, the $SCD_{h}$ and ICD was detectable at and above 100 kPa and 250 kPa, respectively, and the $SCD_{u}$ was less reliable due to spontaneous occurrence. The BBB was found to be disrupted in 250-600 kPa without edema, hemorrhage, and physiological changes were found. In conclusion, the $SCD_{h}$ was more detectable and reliable than the $SCD_{u}$ in assessing stable cavitation in vivo, and the inertial cavitation was detected at 250 kPa and may occur at lower pressures.
Sponsorship	IEEE Ultrason., Ferroelectr., Freq. Control Society
Starting Page	1201
Ending Page	1204
File Size	415705
Page Count	4
File Format	PDF
ISSN	19485719
e-ISBN	9781467356862
DOI	10.1109/ULTSYM.2013.0307
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2013-07-21
Publisher Place	Czech Republic
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	In vivo Monitoring In vitro Ultrasonic imaging Skull Harmonic analysis Reliability primates blood-brain barrier opening focused ultrasound passive cavitation detection skull effect
Content Type	Text
Resource Type	Article

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