TY - JOUR
T1 - An Affordable and Easy-to-Use Focused Ultrasound Device for Noninvasive and High Precision Drug Delivery to the Mouse Brain
AU - Hu, Zhongtao
AU - Chen, Si
AU - Yang, Yaoheng
AU - Gong, Yan
AU - Chen, Hong
N1 - Funding Information:
This work was supported in part by the National Institutes of Health under Grants R01EB027223, R01EB030102, and R01MH116981, in part by the Office of Naval Research under Grant N00014-19-1-2335, in part by the Charlie Teo Foundation, and in part by Little Legs Foundation.
Publisher Copyright:
© 1964-2012 IEEE.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Objective: Focused ultrasound (FUS) combined with microbubble-mediated blood-brain barrier (BBB) opening (FUS-BBBO) is not only a promising technique for clinical applications but also a powerful tool for preclinical research. However, existing FUS devices for preclinical research are expensive, bulky, and lack the precision needed for small animal research, which limits the broad adoption of this promising technique by the research community. Our objective was to design and fabricate an affordable, easy-to-use, high-precision FUS device for small animal research. Methods: We designed and fabricated in-house mini-FUS transducers (∼80 each in material cost) with three frequencies (1.5, 3.0, and 6.0 MHz) and integrated them with a stereotactic frame for precise mouse brain targeting using established stereotactic procedures. The BBB opening volume by FUS at different acoustic pressures (0.20-0.57 MPa) was quantified using T1-weighted contrast-enhanced magnetic resonance imaging of gadolinium leakage and fluorescence imaging of Evans blue extravasation. Results: The targeting accuracy of the device as measured by the offset between the desired target location and the centroid of BBBO was 0.63 ± 0.19 mm. The spatial precision of the device in targeting individual brain structures was improved by the use of higher frequency FUS transducers. The BBB opening volume had high linear correlations with the cavitation index (defined by the ratio between acoustic pressure and frequency) and mechanical index (defined by the ratio between acoustic pressure and the square root of frequency). The correlation coefficient of the cavitation index was slightly higher than that of the mechanical index. Conclusion: This study demonstrated that spatially accurate and precise BBB opening was achievable using an affordable and easy-to-use FUS device. The BBB opening volume was tunable by modulating the cavitation index. This device is expected to decrease the barriers to the adoption of the FUS-BBBO technique by the broad research community.
AB - Objective: Focused ultrasound (FUS) combined with microbubble-mediated blood-brain barrier (BBB) opening (FUS-BBBO) is not only a promising technique for clinical applications but also a powerful tool for preclinical research. However, existing FUS devices for preclinical research are expensive, bulky, and lack the precision needed for small animal research, which limits the broad adoption of this promising technique by the research community. Our objective was to design and fabricate an affordable, easy-to-use, high-precision FUS device for small animal research. Methods: We designed and fabricated in-house mini-FUS transducers (∼80 each in material cost) with three frequencies (1.5, 3.0, and 6.0 MHz) and integrated them with a stereotactic frame for precise mouse brain targeting using established stereotactic procedures. The BBB opening volume by FUS at different acoustic pressures (0.20-0.57 MPa) was quantified using T1-weighted contrast-enhanced magnetic resonance imaging of gadolinium leakage and fluorescence imaging of Evans blue extravasation. Results: The targeting accuracy of the device as measured by the offset between the desired target location and the centroid of BBBO was 0.63 ± 0.19 mm. The spatial precision of the device in targeting individual brain structures was improved by the use of higher frequency FUS transducers. The BBB opening volume had high linear correlations with the cavitation index (defined by the ratio between acoustic pressure and frequency) and mechanical index (defined by the ratio between acoustic pressure and the square root of frequency). The correlation coefficient of the cavitation index was slightly higher than that of the mechanical index. Conclusion: This study demonstrated that spatially accurate and precise BBB opening was achievable using an affordable and easy-to-use FUS device. The BBB opening volume was tunable by modulating the cavitation index. This device is expected to decrease the barriers to the adoption of the FUS-BBBO technique by the broad research community.
KW - blood-brain barrier
KW - brain drug delivery
KW - cavitation index
KW - Focused ultrasound
KW - mechanical index
UR - http://www.scopus.com/inward/record.url?scp=85124835915&partnerID=8YFLogxK
U2 - 10.1109/TBME.2022.3150781
DO - 10.1109/TBME.2022.3150781
M3 - Article
C2 - 35157574
AN - SCOPUS:85124835915
SN - 0018-9294
VL - 69
SP - 2723
EP - 2732
JO - IEEE Transactions on Biomedical Engineering
JF - IEEE Transactions on Biomedical Engineering
IS - 9
ER -