10 results on '"Carlos Sierra Sanchez"'
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2. Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping
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Christian Aurup, Hermes A. S. Kamimura, Wenlan Zheng, Carlos Sierra Sanchez, Julien Grondin, Elisa E. Konofagou, Shih-Ying Wu, and Vincent P. Ferrera
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Male ,Primates ,Neuronavigation ,medicine.medical_treatment ,lcsh:Medicine ,Therapeutics ,Blood–brain barrier ,Article ,030218 nuclear medicine & medical imaging ,Pharmacological treatment ,Sonication ,03 medical and health sciences ,Drug Delivery Systems ,Brain--Diseases--Treatment ,0302 clinical medicine ,medicine ,Animals ,lcsh:Science ,Ultrasonography ,Blood-brain barrier ,Brain Mapping ,Microbubbles ,Multidisciplinary ,business.industry ,lcsh:R ,Ultrasound ,Brain ,Acoustics ,Macaca mulatta ,Magnetic Resonance Imaging ,High-intensity focused ultrasound ,Radiation therapy ,Macaca fascicularis ,medicine.anatomical_structure ,Drug delivery ,lcsh:Q ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.
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- 2018
3. Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring
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Amanda Buch, Carlos Sierra Sanchez, Vincent P. Ferrera, Shih-Ying Wu, Elisa E. Konofagou, and Gesthimani Samiotaki
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Male ,Primates ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Gadolinium ,Blood–brain barrier ,Article ,Focused ultrasound ,030218 nuclear medicine & medical imaging ,White matter ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,biology.animal ,medicine ,Animals ,Primate ,Gray Matter ,Blood-brain barrier ,Multidisciplinary ,biology ,Macaca mulatta ,High-intensity focused ultrasound ,Drug delivery systems ,medicine.anatomical_structure ,Ultrasonic Waves ,Drug delivery ,Microbubbles ,Biomedical engineering ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.
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- 2016
4. 5th International Symposium on Focused Ultrasound
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Menashe Zaaroor, Alon Sinai, Dorit Goldsher, Ayelet Eran, Maria Nassar, Ilana Schlesinger, Jonathon Parker, Vinod Ravikumar, Pejman Ghanouni, Sherman Stein, Casey Halpern, Vibhor Krishna, Amelia Hargrove, Punit Agrawal, Barbara Changizi, Eric Bourekas, Michael Knopp, Ali Rezai, Brian Mead, Namho Kim, Panagiotis Mastorakos, Jung Soo Suk, Wilson Miller, Alexander Klibanov, Justin Hanes, Richard Price, Shutao Wang, Oluyemi Olumolade, Tara Kugelman, Vernice Jackson-Lewis, Maria Eleni Karakatsani, Yang Han, Serge Przedborski, Elisa Konofagou, Kullervo Hynynen, Isabelle Aubert, Gerhard Leinenga, Rebecca Nisbet, Robert Hatch, Anneke Van der Jeugd, Harrison Evans, Jürgen Götz, Ann Van der Jeugd, Paul Fishman, Paul Yarowsky, Victor Frenkel, Shen Wei-Bin, Ben Nguyen, Carlos Sierra Sanchez, Camilo Acosta, Cherry Chen, Shih-Ying Wu, Muna Aryal, Iason T. Papademetriou, Yong-Zhi Zhang, Chanikarn Power, Nathan McDannold, Tyrone Porter, Zsofia Kovacs, Saejeong Kim, Neekita Jikaria, Farhan Qureshi, Michele Bresler, Joseph Frank, Henrik Odéen, George Chiou, John Snell, Nick Todd, Bruno Madore, Dennis Parker, Kim Butts Pauly, Mike Marx, Sumeeth Jonathan, William Grissom, Costas Arvanitis, Gregory Clement, Joshua de Bever, Allison Payne, Douglas Christensen, Guillaume Maimbourg, Mathieu David Santin, Alexandre Houdouin, Stéphane Lehericy, Mickael Tanter, Jean Francois Aubry, Christian Federau, Beat Werner, Dong-Guk Paeng, Zhiyuan Xu, Anders Quigg, Matt Eames, Changzhu Jin, Ashli Everstine, Jason Sheehan, M. Beatriz Lopes, Neal Kassell, James Drake, Karl Price, Lior Lustgarten, Vivian Sin, Charles Mougenot, Elizabeth Donner, Emily Tam, Mojgan Hodaie, Adam Waspe, Thomas Looi, Samuel Pichardo, Wonhye Lee, Yong An Chung, Yujin Jung, In-Uk Song, Seung-Schik Yoo, Hyun-Chul Kim, Jong-Hwan Lee, Charles Caskey, Wolf Zinke, Josh Cosman, Jillian Shuman, Jeffrey Schall, Christian Aurup, Hong Chen, Hermes Kamimura, Antonio Carneiro, Tao Sun, Navid Nazai, Sam Patz, Margaret Livingstone, Todd Mainprize, Yuexi Huang, Ryan Alkins, Martin Chapman, James Perry, Nir Lipsman, Allison Bethune, Arjun Sahgal, Maureen Trudeau, Hao-Li Liu, Po-Hung Hsu, Kuo-Chen Wei, Jonathan Sutton, Phillip Alexander, Eric Miller, Thiele Kobus, Alexandre Carpentier, Michael Canney, Alexandre Vignot, Kevin Beccaria, Delphine Leclercq, Cyril Lafon, Jean Yves Chapelon, Khe Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih, David Moore, Alexis Xu, Paul Schmitt, Jessica Foley, Jonathan Sukovich, Charles Cain, Aditya Pandey, Neeraj Chaudhary, Sandra Camelo-Piragua, Steven Allen, Jon Cannata, Dejan Teofilovic, Jim Bertolina, Timothy Hall, Zhen Xu, Julien Grondin, Vincent Ferrera, Gail ter Haar, Petros Mouratidis, Elizabeth Repasky, Kelsie Timbie, Lena Badr, Benjamin Campbell, John McMichael, Andrew Buckner, Jessica Prince, Aaron Stevens, Timothy Bullock, Karin Skalina, Chandan Guha, Franco Orsi, Guido Bonomo, Paolo Della Vigna, Giovanni Mauri, Gianluca Varano, George Schade, Yak-Nam Wang, Venu Pillarisetty, Joo Ha Hwang, Vera Khokhlova, Michael Bailey, Tatiana Khokhlova, Ilya Sinilshchikov, Petr Yuldashev, Yulia Andriyakhina, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov, Ari Partanen, Jonathan Lundt, Tobias Preusser, Sabrina Haase, Mario Bezzi, Jürgen Jenne, Thomas Langø, Massimo Midiri, Michael Mueller, Giora Sat, Christine Tanner, Stephan Zangos, Matthias Guenther, Andreas Melzer, Arianna Menciassi, Selene Tognarelli, Andrea Cafarelli, Alessandro Diodato, Gastone Ciuti, Sven Rothluebbers, Julia Schwaab, Jan Strehlow, Senay Mihcin, Steffen Tretbar, Thomas Payen, Carmine Palermo, Steve Sastra, Kenneth Olive, Matthew Adams, Vasant Salgaonkar, Serena Scott, Graham Sommer, Chris Diederich, Joan Vidal-Jove, Eloi Perich, Antonio Ruiz, Manuela Velat, David Melodelima, Aurelien Dupre, Jeremy Vincenot, Chen Yao, David Perol, Michel Rivoire, Samantha Tucci, Lisa Mahakian, Brett Fite, Elizabeth Ingham, Sarah Tam, Chang-il Hwang, David Tuveson, Katherine Ferrara, Stephen Scionti, Lili Chen, Dusica Cvetkovic, Xiaoming Chen, Roohi Gupta, Bin Wang, Charlie Ma, Kenneth Bader, Kevin Haworth, Christy Holland, Narendra Sanghvi, Roy Carlson, Wohsing Chen, Christian Chaussy, Stefan Thueroff, Claudio Cesana, Carlo Bellorofonte, Qingguo Wang, Han Wang, Shengping Wang, Junhai Zhang, Alberto Bazzocchi, Alessandro Napoli, Robert Staruch, Chenchen Bing, Sumbul Shaikh, Joris Nofiele, Debra Szczepanski, Michelle Wodzak Staruch, Noelle Williams, Theodore Laetsch, Rajiv Chopra, Jarrett Rosenberg, Rachelle Bitton, Suzanne LeBlang, Joshua Meyer, Mark Hurwitz, Pavel Yarmolenko, Haydar Celik, Avinash Eranki, Viktoriya Beskin, Domiciano Santos, Janish Patel, Matthew Oetgen, AeRang Kim, Peter Kim, Karun Sharma, Alexander Chisholm, Dionne Aleman, Roberto Scipione, Michael Temple, Joao Guilherme Amaral, Ruby Endre, Maria Lamberti-Pasculli, Joost de Ruiter, Fiona Campbell, Jennifer Stimec, Samit Gupta, Manoj Singh, Sevan Hopyan, Gregory Czarnota, David Brenin, Carrie Rochman, Roussanka Kovatcheva, Jordan Vlahov, Katja Zaletel, Julian Stoinov, Matthew Bucknor, Viola Rieke, Jenny Shim, Korgun Koral, Brian Lang, Carlos Wong, Heather Lam, Alexander Shinkov, Jim Hu, Xi Zhang, Jonathan Macoskey, Kimberly Ives, Gabe Owens, Hitinder Gurm, Jiaqi Shi, Matthew Pizzuto, Christopher Dillon, Ivy Christofferson, Elaine Hilas, Jill Shea, Paul Greillier, Bénédicte Ankou, Francis Bessière, Ali Zorgani, Mathieu Pioche, Wojciech Kwiecinski, Julie Magat, Sandrine Melot-Dusseau, Romain Lacoste, Bruno Quesson, Mathieu Pernot, Stefan Catheline, Philippe Chevalier, Fabrice Marquet, Pierre Bour, Fanny Vaillant, Sana Amraoui, Rémi Dubois, Philippe Ritter, Michel Haïssaguerre, Mélèze Hocini, Olivier Bernus, Pamela Tebebi, Scott Burks, Blerta Milo, Michael Gertner, Jimin Zhang, Andrew Wong, Yu Liu, Azadeh Kheirolomoom, Jai Seo, Katherine Watson, Hua Zhang, Josquin Foiret, Alexander Borowsky, Doudou Xu, Maya Thanou, Miguell Centelles, Mike Wright, Maral Amrahli, Po-Wah So, Wladyslaw Gedroyc, Esther Kneepkens, Edwin Heijman, Jochen Keupp, Steffen Weiss, Klaas Nicolay, Holger Grüll, Matthew Nagle, Anastasia V. Nikolaeva, Marina E. Terzi, Sergey A. Tsysar, Bryan Cunitz, Pierre Mourad, Matthew Downs, Georgiana Yang, Qi Wang, Johnny Chen, Justin Farry, Adam Dixon, Zhongmin Du, Ali Dhanaliwala, John Hossack, Ashish Ranjan, Danny Maples, Rachel Wardlow, Jerry Malayer, Akhilesh Ramachandran, Hirofumi Namba, Motohiro Kawasaki, Masashi Izumi, Katsuhito Kiyasu, Ryuichi Takemasa, Masahiko Ikeuchi, Takahiro Ushida, Calum Crake, Satya V. V. N. Kothapalli, Wan Leighton, Zhaorui Wang, H. Michael Gach, William Straube, Michael Altman, Young-sun Kim, Hyo Keun Lim, Hyunchul Rhim, Johanna van Breugel, Manon Braat, Chrit Moonen, Maurice van den Bosch, Mario Ries, Cristina Marrocchio, Susan Dababou, Jae Young Lee, Hyun Hoon Chung, Soo Yeon Kang, Kook Jin Kang, Keon Ho Son, Dandan Zhang, Juan Plata, Peter Jones, Aurea Pascal-Tenorio, Donna Bouley, Aaron Bond, Robert Dallapiazza, Diane Huss, Amy Warren, Scott Sperling, Ryder Gwinn, Binit Shah, W. Jeff Elias, Colleen Curley, Ying Zhang, Karina Negron, Roger Abounader, Gesthimani Samiotaki, Tsang-Wei Tu, Georgios Papadakis, Dima Hammoud, Matthew Silvestrini, Frank Wolfram, Daniel Güllmar, Juergen Reichenbach, Denis Hofmann, Joachim Böttcher, Harald Schubert, Thomas G. Lesser, Scott Almquist, Francisco Camarena, Sergio Jiménez-Gambín, Noé Jiménez, Jin Woo Chang, Vandiver Chaplin, Rebekah Griesenauer, Michael Miga, Nicholas Ellens, Raag Airan, Alfredo Quinones-Hinojosa, Keyvan Farahani, Xue Feng, Samuel Fielden, Li Zhao, Max Wintermark, Craig Meyer, Sijia Guo, Xin Lu, Jiachen Zhuo, Su Xu, Rao Gullapalli, Dheeraj Gandhi, Omer Brokman, Hongchae Baek, Hyungmin Kim, Steven Leung, Taylor Webb, Natalia Vykhodtseva, Thai-Son Nguyen, Chang Kyu Park, Sang Man Park, Na Young Jung, Min Soo Kim, Won Seok Chang, Hyun Ho Jung, Michael Plaksin, Yoni Weissler, Shy Shoham, Eitan Kimmel, Pavel B. Rosnitskiy, Steve Krupa, Eilon Hazan, Omer Naor, Yoav Levy, Noam Maimon, Inbar Brosh, Itamar Kahn, Jessica Cahill, Elodie Constanciel Colas, Adrian Wydra, Roman Maev, Amirah Aly, Ozge Sesenoglu-Laird, Linas Padegimas, Mark Cooper, Barbara Waszczak, Seruz Tehrani, Craig Slingluff, James Larner, Kumari Andarawewa, Eugene Ozhinsky, Rutwik Shah, Roland Krug, Roel Deckers, Sabine Linn, Britt Suelmann, Arjen Witkamp, Paul Vaessen, Paul van Diest, Lambertus W. Bartels, Clemens Bos, Nicolas Borys, Gert Storm, Elsken Van der Wall, Navid Farr, Moez Alnazeer, Prateek Katti, Bradford Wood, Alexis Farrer, Cyril Ferrer, Baudouin Denis de Senneville, Marijn van Stralen, Jingfei Liu, J. Kent Leach, Stephan Zidowitz, Hsin-Lun Lee, Fang-Chi Hsu, Chia-Chun Kuo, Shiu-Chen Jeng, Tung-Ho Chen, Nai-Yi Yang, Jeng-Fong Chiou, Yi-tzu Kao, Chia-Hsin Pan, Jing-Fu Wu, Yi-Chieh Tsai, Sara Johnson, Dawei Li, Ye He, Ioannis Karakitsios, Michael Schwenke, Daniel Demedts, Xu Xiao, Ian Cavin, Emilee Minalga, Robb Merrill, Rock Hadley, Pascal Ramaekers, Martijn de Greef, Kian Shahriari, Mohammad Hossein Parvizi, Kiana Asadnia, Marzieh Chamanara, Seyed Kamran Kamrava, Hamid Reza Chabok, Ruben Stein, Sébastien Muller, Jeremy Tan, Cornel Zachiu, Hans-Peter Erasmus, Glen Van Arsdell, Lee Benson, Kee W. Jang, Mary Angstadt, Bobbi Lewis, Hailey McLean, Martijn Hoogenboom, Dylan Eikelenboom, Martijn den Brok, Pieter Wesseling, Arend Heerschap, Jurgen Fütterer, Gosse Adema, Kevin Wang, Pei Zhong, Joyce Joy, Helen McLeod, Harry Kim, Matthew Lewis, Arda Ozilgen, Peter Zahos, Dezba Coughlin, Xinyan Tang, Jeff Lotz, Kathleen Jedruszczuk, Amitabh Gulati, Stephen Solomon, Elena Kaye, John Mugler, Gaetano Barbato, Gian Luca Scoarughi, Cristiano Corso, Alessandro Gorgone, Ilaria Giuseppina Migliore, Zachary Larrabee, Arik Hananel, Jean-Francois Aubry, Ayele Negussie, Emmanuel Wilson, Reza Seifabadi, Hyungwon Moon, Jeeun Kang, Changbeom Sim, Jin Ho Chang, Hyuncheol Kim, Hak Jong Lee, Noboru Sasaki, Mitsuyoshi Takiguchi, Lukas Sebeke, Xi Luo, Bram de Jager, Maurice Heemels, Christopher Abraham, Laura Curiel, Rémi Berriet, Margit Janát-Amsbury, Joseph Corea, Patrick Peiyong Ye, Ana Clauda Arias, Micheal Lustig, and Bryant Svedin
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Pathology ,medicine.medical_specialty ,business.industry ,Blood–brain barrier ,Focused ultrasound ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Disease therapy ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,Radiology, Nuclear Medicine and imaging ,business ,030217 neurology & neurosurgery - Published
- 2016
5. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor
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Elisa E. Konofagou, Hoheteberhan Getachew, Hong Chen, Camilo Acosta, Carlos Sierra Sanchez, and Georgiana Yang
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0301 basic medicine ,Drug ,Male ,Pathology ,medicine.medical_specialty ,media_common.quotation_subject ,Central nervous system ,Pharmacology ,Blood–brain barrier ,Article ,03 medical and health sciences ,Mice ,Sonication ,0302 clinical medicine ,Drug Delivery Systems ,Neurotrophic factors ,medicine ,Animals ,Administration, Intranasal ,media_common ,Brain-derived neurotrophic factor ,Multidisciplinary ,business.industry ,Brain-Derived Neurotrophic Factor ,Brain ,Dextrans ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Blood-Brain Barrier ,Nanoparticles for drug delivery to the brain ,Drug delivery ,Nasal administration ,business ,030217 neurology & neurosurgery - Abstract
The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.
- Published
- 2016
6. ANALYSIS OF THE INITIAL UNITED STATES EXPERIENCE WITH THE BIOTRACE TEMPO TEMPORARY PACING LEAD IN TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) AND OTHER CARDIAC PROCEDURES
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Martin B. Leon, John Forrest, Brian Whisenant, Daniel Menees, James Orford, Arash Arshi, Susheel Kodali, Carlos Sierra Sanchez, Juan Terre, Tamim Nazif, Stanley Chetcuti, Steven J. Yakubov, and Paul Grossman
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Heart procedures ,medicine.medical_specialty ,Transcatheter aortic ,business.industry ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Transvenous pacing ,03 medical and health sciences ,0302 clinical medicine ,Valve replacement ,Cardiac Perforation ,Internal medicine ,Cardiac procedures ,medicine ,Cardiology ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,Lead (electronics) ,business - Abstract
The use of temporary pacing has increased dramatically with the rapid growth of TAVR and other structural heart procedures. Complications of temporary transvenous pacing leads include dislodgement causing loss of pace capture, arrhythmias and cardiac perforation. We report the results of a multi
- Published
- 2018
7. Focused-ultrasound mediated anti-alpha-synuclein antibody delivery for the treatment of Parkinson’s disease
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Carlos Sierra Sanchez, Elisa E. Konofagou, Nancy Kwon, Hairong Zhang, Serge Przedborski, and Vernice Jackson-Lewis
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Alpha-synuclein ,Genetically modified mouse ,Parkinson's disease ,Acoustics and Ultrasonics ,business.industry ,medicine.drug_class ,Pars compacta ,animal diseases ,Transgene ,Dopaminergic ,Substantia nigra ,Monoclonal antibody ,medicine.disease ,nervous system diseases ,chemistry.chemical_compound ,nervous system ,Arts and Humanities (miscellaneous) ,chemistry ,Cancer research ,Medicine ,business - Abstract
Parkinson’s disease (PD) is associated with the selective death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the specific cause of the neuronal loss remains elusive, the abnormal accumulation of alpha synuclein (α-syn), a major constituent of Lewy bodies, is considered to play a central role in the pathology of PD. Previous studies have shown the potential of immunotherapy with antibodies against α-syn, but such treatments remain ineffective due to the presence of the blood-brain barrier (BBB), which hinders most therapeutic agents to diffuse to the brain parenchyma. Therefore, in this study, we used focused ultrasound (FUS) in conjunction with microbubbles to transiently and noninvasively open the BBB and deliver anti-α-syn monoclonal antibodies (mAb) to the brains of transgenic PD mouse models. Preliminary histological findings demonstrate that the FUS promotes the delivery of anti-α-syn mAb to the transgenic mice overexpressing the human A53T or A30P α-synuclein. We ...
- Published
- 2017
8. Monitoring of focused ultrasound-induced blood-brain barrier opening in non-human primates using transcranial cavitation detection in vivo and the primate skull effect
- Author
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Yao-Sheng Tung, Tobias Teichert, Amanda Buch, Elisa E. Konofagou, Gesthemani Samiotaki, Matthew Downs, Fabrice Marquet, Vincent P. Ferrera, Cherry C. Chen, Carlos Sierra Sanchez, and Shih-Ying Wu
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Skull ,Materials science ,medicine.anatomical_structure ,In vivo ,Sonication ,Cavitation ,medicine ,Microbubbles ,Pulse duration ,Blood–brain barrier ,Imaging phantom ,Biomedical engineering - 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 (SCDh) and ultraharmonics (SCDu) and the inertial cavitation dose (ICD) were quantified. Results showed that the SCDh, SCDu, 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 SCDh and ICD was detectable at and above 100 kPa and 250 kPa, respectively, and the SCDu 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 SCDh was more detectable and reliable than the SCDu in assessing stable cavitation in vivo, and the inertial cavitation was detected at 250 kPa and may occur at lower pressures.
- Published
- 2013
9. Focused ultrasound-enhanced intranasal delivery of brain-derived neurotrophic factor
- Author
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Hong Chen, Carlos Sierra Sanchez, Hoheteberhan Getachew, Camilo Acosta, Elisa E. Konofagou, and Georgiana Yang
- Subjects
Brain-derived neurotrophic factor ,Acoustics and Ultrasonics ,business.industry ,Central nervous system ,Pharmacology ,Focused ultrasound ,medicine.anatomical_structure ,Arts and Humanities (miscellaneous) ,Neurotrophic factors ,Microbubbles ,medicine ,Immunohistochemistry ,Nasal administration ,Perivascular space ,business - Abstract
The therapeutic use of neurotrophic factors in the treatment of central nervous system diseases has been restrained by their low blood-barrier permeability and rapid degradation in the blood. Intranasal (IN) administration is a promising approach for delivering neurotrophic factors directly to the brain, bypassing the BBB. However, IN delivery has low efficiency and does not offer localized delivery to specific brain sites. The objective of this study was to demonstrate the feasibility of FUS-enhanced IN delivery of brain derived neurotrophic factor (BDNF) at a targeted location. BDNF was administered through IN route in wild-type mice (n = 7) followed by FUS sonication at the left caudaputamen in the presence of systemically circulating microbubbles. The contralateral right caudaputamen was used as control for IN delivery only. Immunohistochemistry staining was used to assess the distribution of BDNF and the bioactivity of BDNF in activating the downstream signaling. It was found that FUS enhanced the delivery efficiency of IN administered BDNF at the targeted region, where BDNF penetrated deep into the brain tissue instead of confining within the perivascular spaces as in the contralateral control side. Furthermore, the delivered BDNF reached sufficient concentration to activate the downstream signaling pathway.
- Published
- 2015
10. Behavioral effects of targeted drug delivery via non-invasive microbubble enhanced focused ultrasound blood brain barrier opening in non-human primates
- Author
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Matthew Downs, Shangshang Chen, Maria Eleni Karakatsani, Amanda Buch, Carlos Sierra Sanchez, Elisa E. Konofagou, and Vincent P. Ferrera
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business.industry ,Neurogenesis ,Non invasive ,food and beverages ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Blood–brain barrier ,Bioinformatics ,030226 pharmacology & pharmacy ,humanities ,Focused ultrasound ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Targeted drug delivery ,Drug delivery ,Poster Presentation ,Microbubbles ,Medicine ,Radiology, Nuclear Medicine and imaging ,0210 nano-technology ,business ,Neuroscience - Abstract
The Blood Brain Barrier (BBB) in Non-Human Primates (NHP) can be non-invasively opened through the use of Focused Ultrasound (FUS) in conjunction with microbubbles. This procedure allows for a targeted, transient opening in the BBB of the NHP which can be utilized to facilitate drug delivery. While FUS has been used to deliver various pharmacological compounds to promote neurogenesis or treat cancer, no group has investigated if drug delivery can affect behavioral responses. In this study, we show the effects of targeted ME-FUS drug delivery on the responses of NHP to a decision making task.
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