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Incidence angle and gray-to-white-matter ratio dependence of the focused-ultrasound induced blood-brain barrier opening in non-human primates
© Karakatsani et al; licensee BioMed Central Ltd. 2015
Published: 30 June 2015
FUS coupled with the systemic administration of microbubbles has been proved to open the Blood-Brain Barrier (BBB) locally, transiently and non-invasively in non-human primates (NHP). However, the complexity of the NHP brain constitutes an obstacle in relating the volume size of the induced opening (VBBB) to the geometric aspects of the method as well as the physiologic characteristics of the targeted areas. The objective of the current study is to quantify the correlation between the VBBB, the FUS pressure and the incidence angle. Additionally, the dependence of the opening shift on the gray-to-white-matter ratio at the targeted area is studied.
Results and conclusions
VBBB increased from 106.79±50 mm3 to 305.7±50 mm3 at an incidence angle range of 73.67 ± 0.19° to 89.83 ± 0.19° at 300kPa, respectively. Similar increase was obtained at other pressures suggesting a linear correlation between the three aforementioned components. The squared correlation coefficient (R2) varied from 0.71 to 0.97 when studying each NHP separately. The opening in the GM accounted for an average of 88.5±8.9% of the opening cases when targeting the Pu, while 78.3±6.6% occurred in the GM when focusing on the Cau. In conclusion, the VBBB was found to strongly depend on both the incidence angle and the pressure applied. It was also concluded that the shift in the BBB opening region from the targeted one depends on the gray-to-white-matter ratio present in the focal region.
The authors would like to thank Shih Ying Wu, Carlos Sierra Sanchez and Amanda Marie Buch for their contribution. This study was supported by the National Institutes of Health (AG038961 and EB009041), the Focused Ultrasound Foundation and the W.H. Coulter Foundation.
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