Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors
February 5, 2021 — Science Advances
Focused ultrasound (FUS) in the presence of microbubbles can transiently open the blood-brain barrier (BBB) to increase therapeutic agent penetration at the targeted brain site to benefit recurrent glioblastoma (rGBM) treatment. This study is a dose-escalating pilot trial using a device combining neuronavigation and a manually operated frameless FUS system to treat rGBM patients. The safety and feasibility were established, while a dose-dependent BBB-opening effect was observed, which reverted to baseline within 24 hours after treatment. No immunological response was observed clinically under the applied FUS level in humans; however, selecting a higher level in animals resulted in prolonged immunostimulation, as confirmed preclinically by the recruitment of lymphocytes into the tumor microenvironment (TME) in a rat glioma model. Our findings provide preliminary evidence of FUS-induced immune modulation as an additional therapeutic benefit by converting the immunosuppressive TME into an immunostimulatory TME via a higher but safe FUS dosage.
Authors; Ko-Ting Chen1,2, Wen-Yen Chai3, Ya-Jui Lin1,4, Chia-Jung Lin5, Pin-Yuan Chen6,7, Hong-Chieh Tsai1, Chiung-Yin Huang8, John S. Kuo9, Hao-Li Liu5, Kuo-Chen Wei1,7,8,
1Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
2Ph.D. Program in Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.
3Department of Diagnostic Radiology and Intervention, Chang Gung Memorial Hospital at LinKou, Taoyuan, Taiwan.
4The Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
5Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
6Department of Neurosurgery, Chang Gung Memorial Hospital at Keelung, Taiwan.
7School of Medicine, Chang Gung University, Taoyuan, Taiwan.
8Department of Neurosurgery, New Taipei Municipal TuCheng Hospital, Chang Gung Medical Foundation, New Taipei, Taiwan.
9Department of Neurosurgery and Mulva Clinic for the Neurosciences, Dell Medical School, The University of Texas at Austin, USA.
Read full text at: Vol. 7, no. 6, eabd0772; DOI: 10.1126/sciadv.abd0772