Abstract
Blood brain barrier (BBB) is a major barrier for delivering therapeutic agents in the brain. In this study we investigated the feasibility of open the BBB by using focused ultrasound. Rabbit brains were exposed to pulsed focused ultrasound while injecting ultrasound contrast agent containg microbubbles intravenously. The BBB opening was measured after the sonications by injecting MRI contrast agent IV and evaluating the local enhancement in the brain. Low ultrasound powers and pressure amplitudes were found to cause focal enhancement. Before sacrificing the animals trypan blue was also injected IV. After the sacrifice of the animals blue spots were found in the brain in the sonicated locations. This method may have potential for targeted delivery of macromolecules in the brain.
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References
Abbott NJ, Romero IA (1996) Transporting therapeutics across the blood brain barrier. Mol Med Today 2: 106–113
Dalecki D, Raeman CH, Child SZ, Cox C, Francis CW, Meltzer RS et al (1997) Hemolysis in vivo from exposure to pulsed ultrasound. Ultrasound Med Biol 23: 307–
Dalecki D, Raeman CH, Child SZ, Penney DP, Mayer R, Carstensen EL (1997) The influence of contrast agents on hemorrhage produced by lithotripter fields. Ultrasound Med Biol 23: 1435–1439
Doolittle ND, Miner ME, Hall WA, Siegal T, Jerome E, Osztie E et al (2000) Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood brain barrier for the treatment of patients with malignant brain tumors. Cancer Feb 1, 88(3): 637–647
Hynynen K, Freund W, Cline HE, Chung A, Watkins R, Vetro J et al (1996) A clinical noninvasive MRI monitored ultrasound surgery method. RadioGraphies 16: 185–195
Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA (2001) Noninvasive MR imaging guided focal opening of the blood brain barrier in rabbits. Radiology 220: 640–646
Kroll RA, Neuwelt EA (1998) Outwitting the blood brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42: 1083–1099
Kuroda K, Chung A, Hynynen K, Jolesz FA (1998) Calibration of water proton chemical shift with temperature for noninvasive temperature imaging during focused ultrasound surgery. JMRI 8: 175–181
Miller DL, Thomas RM (1996) Contrast agent gas bodies enhance hemolysis induced by lithotripter shock waves and high intensity focused ultrasound in whole blood. Ultrasound Med Biol 22: 1089–1095
Qureshi NH, Chiocca EA (1999) A review of gene therapy for the treatment of central nervous system tumors. Crit Rev Oncog 10: 261–274
Vykhodtseva N, Sorrentino V, Jolesz FA, Bronson RT, Hynynen K (2000) MRI detection of the thermal effects of focused ultrasound on the brain. Ultrasound Med Biol Jun 1, 26(5): 871–880
Vykhodtseva NI, Hynynen K, Damianou C (1995) Histologic effects of high intensity pulsed ultrasound exposure with subharmonic emission in rabbit brain in vivo. Ultrasound Med Biol 21: 969–979
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© 2003 Springer-Verlag Wien
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Hynynen, K., McDannold, N., Vykhodtseva, N., Jolesz, F.A. (2003). Non-invasive opening of BBB by focused ultrasound. In: Kuroiwa, T., et al. Brain Edema XII. Acta Neurochirurgica Supplements, vol 86. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0651-8_113
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DOI: https://doi.org/10.1007/978-3-7091-0651-8_113
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-7220-9
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