Pharmacokinetic analysis and drug delivery efficiency of the focused ultrasound-induced blood-brain barrier opening in non-human primates.
Open accessAbstract
Purpose Focused Ultrasound (FUS) in conjunction with systemically administered microbubbles has been shown to open the Blood-Brain Barrier (BBB) locally, non-invasively and reversibly in rodents and non-human primates (NHP), suggesting the immense potential of this technique. The objective of this study entailed the investigation of the physiologic changes in the brain following the FUS-induced BBB opening and their relationship with the underlying anatomy. Materials and methods Pharmacokinetic analysis was implemented in NHP's that received FUS at various acoustic pressures. Relaxivity mapping enabled the robust quantitative detection of the BBB opening as well as grey and white matter segmentation. Drug delivery efficiency was measured for pre-clinical validation of the technique. Results Based on our results, the opening volume and the amount of the gadolinium delivered were found mostly contained in the grey matter, while FUS-induced permeability and drug concentration varied depending upon the underlying brain inhomogeneity, and increased with the acoustic pressure. Conclusions Overall, apart from the in vivo protocols for BBB analysis developed here, this study also suggests the important role that FUS can have in efficient drug delivery via localized and transient BBB opening.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The BBB may also be opened using intravenous mannitol and ultrasound, externally delivered.
“The BBB may also be opened using intravenous mannitol (an old method) and ultrasound, externally delivered (Samiotaki et al., 2017; Wang et al., 2017).”
From Human Brain/Cloud Interface (2019) · cites this paper as Samiotaki et al., 2017
The Introduction says focused ultrasound can open the BBB, and Methods §2.2 describes transcranial ultrasound in rhesus macaques. The intravenously administered agent in that procedure was microbubbles, not mannitol; our copy does not support the mannitol part of the citing sentence. Page numbers were not available in the indexed passages. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1995) · Cited by 1,979 · see citing works
Tofts, P. S., & Kermode, A. G. (1991) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910170208 · Cited by 1,458 · see citing works
Swift, T. J., & Connick, R. E. (1962) · The Journal of Chemical Physics · doi:10.1063/1.1701321 · Cited by 1,297 · see citing works
McDannold, N. J., Arvanitis, C., Vykhodtseva, N. I., & Livingstone, M. S. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0128 · Cited by 588 · see citing works
Parkinson’s disease: animal models and dopaminergic cell vulnerability
Blesa, J., & Przedborski, S. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00155 · Cited by 483 · see citing works
Microbubble size isolation by differential centrifugation
Feshitan, J. A., Chen, C., Kwan, J. J., & Borden, M. A. (2008) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2008.09.066 · Cited by 447 · see citing works
Rapid calculation of T1 using variable flip angle gradient refocused imaging
Fram, E. K., Herfkens, R. J., Johnson, G. A., Glover, G. H., Karis, J. P., Shimakawa, A. S., Perkins, T. G., & Pelc, N. J. (1987) · Magnetic Resonance Imaging · doi:10.1016/0730-725x(87)90021-x · Cited by 388 · see citing works
Key factors in the acquisition of contrast kinetic data for oncology
Evelhoch, J. L. (1999) · Journal of Magnetic Resonance Imaging · doi:10.1002/(sici)1522-2586(199909)10:3 · Cited by 366 · see citing works
An analysis of fast imaging sequences with steady‐state transverse magnetization refocusing
Zur, Y., Stokar, S., & Bendel, P. (1988) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910060206 · Cited by 253 · see citing works
Marty, B., Larrat, B., Landeghem, M. V., Pujolle-Robic, C., Robert, P., Port, M., Bihan, D. L., Pernot, M., Tanter, M., Lethimonnier, F., et al. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.100 · Cited by 201 · see citing works
Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Oncology
Jackson, A., Buckley, D. L., & Parker, G. J. M. (2005) · Medical radiology · doi:10.1007/b137553 · Cited by 181 · see citing works
Samiotaki, G., Vlachos, F., Tung, Y., & Konofagou, E. E. (2011) · Magnetic Resonance in Medicine · doi:10.1002/mrm.23063 · Cited by 173 · see citing works
Self-citationNoninvasive, Transient and Selective Blood-Brain Barrier Opening in Non-Human Primates In Vivo
Marquet, F., Tung, Y., Teichert, T., Ferrera, V. P., & Konofagou, E. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022598 · Cited by 152 · see citing works
Self-citationTung, Y.-S., Marquet, F., Teichert, T., Ferrera, V., & Konofagou, E. E. (2011) · Applied Physics Letters · doi:10.1063/1.3580763 · Cited by 119 · see citing works
Self-citationVlachos, F., Tung, Y., & Konofagou, E. E. (2011) · Magnetic Resonance in Medicine · doi:10.1002/mrm.22848 · Cited by 110 · see citing works
Self-citationSamiotaki, G., & Konofagou, E. E. (2013) · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control · doi:10.1109/tuffc.2013.6644731 · Cited by 104 · see citing works
Self-citationWu, S.-Y., Tung, Y., Marquet, F., Downs, M. E., Sánchez, C. S., Chen, C. C., Ferrera, V. P., & Konofagou, E. E. (2014) · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control · doi:10.1109/tuffc.2014.2992 · Cited by 102 · see citing works
Self-citationVlachos, F., Tung, Y.-S., & Konofagou, E. E. (2010) · Physics in Medicine and Biology · doi:10.1088/0031-9155/55/18/012 · Cited by 86 · see citing works
Self-citationTracer Kinetic Modelling for T1-Weighted DCE-MRI
Parker, G. J. M., & Buckley, D. L. (2005) · Springer eBooks · doi:10.1007/3-540-26420-5_6 · Cited by 56 · see citing works
Grondin, R., Zhang, Z., Ai, Y., Ding, F., Walton, A., Surgener, S. P., Gerhardt, G. A., & Gash, D. M. (2008) · Cell Transplantation · doi:10.3727/096368908784423256 · Cited by 52 · see citing works
Detection of myocardial infarction in the mini‐pig using NMR imaging
Checkley, D., Loveday, B. E., Waterton, J. C., Zhu, X., & Isherwood, I. (1987) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910050302 · Cited by 24 · see citing works
Flagged first, then by citations
3 of the 24 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [10]Tung YS Marquet F Teichert T Ferrera VP Konofagou EE Feasibility of noninvasive cavitation-guided blood-brain barrier opening using focused ultrasound and microbubbles in nonhuman primates Appl Phys Lett 2011 98 16 163704 21580802 PMC3094460
- [16]Tofts PS Brix G Buckley DL Evelhoch JL Henderson E Knopp MV Larsson HB Lee TY Mayr NA Parker GJ Port RE Taylor J Weisskoff RM Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols Magn Reson Med 1999 10 3 223 232 10508281
Cited by
Sorted by citations
Current Strategies for Brain Drug Delivery
Dong, X. (2018) · Theranostics · doi:10.7150/thno.21254 · Cited by 954 · see citing works
“The brain inhomogeneity and acoustic pressure determined the level of BBB opening and consequently the drug concentration in the brain [88].”
BackgroundCurrent Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier
Teleanu, R. I., Preda, M. D., Niculescu, A.-G., Vladâcenco, O., Radu, C. I., Grumezescu, A. M., & Teleanu, D. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14050987 · Cited by 200 · see citing works
Lee, H., Kim, H., Han, H., Lee, M.-J., Lee, S.-H., Yoo, H., Chang, J., & Kim, H. (2017) · Biomedical Engineering Letters · doi:10.1007/s13534-017-0016-5 · Cited by 122 · see citing works
McMahon, D., Poon, C., & Hynynen, K. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1567490 · Cited by 94 · see citing works
Martins, N. R. B., Angelica, A., Chakravarthy, K., Svidinenko, Y., Boehm, F. J., Opris, I., Lebedev, M. A., Swan, M., Garan, S. A., Rosenfeld, J. V., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00112 · Cited by 91 · see citing works
Combining brain perturbation and neuroimaging in non-human primates
Klink, P. C., Aubry, J., Ferrera, V. P., Fox, A. S., Froudist‐Walsh, S., Jarraya, B., Konofagou, E. E., Krauzlis, R. J., Messinger, A., Mitchell, A. S., et al. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118017 · Cited by 86 · see citing works
Self-citationDauba, A., Delalande, A., Kamimura, H. A. S., Conti, A., Larrat, B., Tsapis, N., & Novell, A. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12111125 · Cited by 83 · see citing works
McMahon, D., Oakden, W., & Hynynen, K. (2020) · Theranostics · doi:10.7150/thno.40908 · Cited by 57 · see citing works
Blood–brain barrier opening with focused ultrasound in experimental models of Parkinson's disease
Karakatsani, M. E., Blesa, J., & Konofagou, E. E. (2019) · Movement Disorders · doi:10.1002/mds.27804 · Cited by 57 · see citing works
Self-citationvan den Broek, S. L., Shalgunov, V., & Herth, M. M. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.213125 · Cited by 56 · see citing works
The road ahead to successful BBB opening and drug-delivery with focused ultrasound
López‐Aguirre, M., Castillo-Ortiz, M., Viña-González, A., Blesa, J., & Pineda‐Pardo, J. A. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.07.006 · Cited by 49 · see citing works
Focused ultrasound opening of the blood–brain barrier for treatment of Parkinson's disease
LeWitt, P. A., Lipsman, N., & Kordower, J. H. (2019) · Movement Disorders · doi:10.1002/mds.27722 · Cited by 45 · see citing works
Cammalleri, A., Croce, P., Lee, W., Yoon, K., & Yoo, S. (2020) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0000000000000488 · Cited by 38 · see citing works
Yoon, K., Lee, W., Chen, E., Lee, J. E., Croce, P., Cammalleri, A., Foley, L., Tsao, A. L., & Yoo, S. (2019) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2019.05.023 · Cited by 37 · see citing works
Modulation of Brain Function and Behavior by Focused Ultrasound
Muñoz, F., Aurup, C., Konofagou, E. E., & Ferrera, V. P. (2018) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-018-0156-7 · Cited by 36 · see citing works
Self-citationFocused shockwave induced blood-brain barrier opening and transfection
Kung, Y., Chiang, L., Hsiao, M., Sun, M., Hsu, Y.-H., Huang, A. P., Liao, W., Liu, H.-L., Inserra, C., & Chen, W. (2018) · Scientific Reports · doi:10.1038/s41598-018-20672-y · Cited by 33 · see citing works
Drug delivery and targeting to brain tumors: considerations for crossing the blood-brain barrier
Omidi, Y., Kianinejad, N., Kwon, Y. M., & Omidian, H. (2021) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2021.1887729 · Cited by 31 · see citing works
Magnetic Resonance Methods for Focused Ultrasound-Induced Blood-Brain Barrier Opening
Conti, A., Kamimura, H. A. S., Novell, A., Duggento, A., & Toschi, N. (2020) · Frontiers in Physics · doi:10.3389/fphy.2020.547674 · Cited by 22 · see citing works
A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
Kung, Y., Huang, H.-Y., Liao, W., Huang, A. P., Hsiao, M., Wu, C., Liu, H.-L., Inserra, C., & Chen, W. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00402 · Cited by 21 · see citing works
Rouhi, N., Chakeri, Z., Ghorbani Nejad, B., Rahimzadegan, M., Rafi Khezri, M., Kamali, H., & Nosrati, R. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37533 · Cited by 20 · see citing works
Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer
Antoniou, A., Evripidou, N., & Damianou, C. (2023) · Journal of Ultrasound · doi:10.1007/s40477-023-00810-7 · Cited by 18 · see citing works
Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array
Manuel, T. J., Sigona, M. K., Phipps, M. A., Kusunose, J., Luo, H., Yang, P., Newton, A. T., Gore, J. C., Grissom, W. A., Chen, L. M., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.10.015 · Cited by 16 · see citing works
MR-guided blood-brain barrier opening induced by rapid short-pulse ultrasound in non-human primates
Zhou, H., Liu, Y., Long, X., Qiao, Y., Lee, J., Liu, X., Zheng, H., & Zou, C. (2021) · Quantitative Imaging in Medicine and Surgery · doi:10.21037/qims-20-1047 · Cited by 10 · see citing works
Feasibility of Ultrasonic Heating through Skull Phantom Using Single-element Transducer
Antoniou, A., & Damianou, C. (2023) · Journal of Medical Ultrasound · doi:10.4103/jmu.jmu_3_23 · Cited by 7 · see citing works
Imaging strategies to assess efficacy and safety of ultrasound-induced blood-brain barrier opening
Pagé, G., Novell, A., & Larrat, B. (2025) · npj Acoustics · doi:10.1038/s44384-025-00024-7 · Cited by 10 · see citing works
Zhou, H., Liu, Y., Long, X., Qiao, Y., Lee, J., Peng, H., Liu, X., Zou, C., & Zheng, H. (2021) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2021.109383 · Cited by 6 · see citing works
Advances in ultrasound-mediated brain drug delivery
Wang, Y., Wen, Q., Hu, A., Chen, X., Liu, J., Lin, J., & Xie, Y. (2025) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgaf090 · Cited by 4 · see citing works
Davidson, B., Schmidt, F. A., Bichsel, O., Hajiabadi, M. M., & Lozano, A. M. (2025) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2025.3624970 · Cited by 6 · see citing works
Hývlová, D., Jiřík, R., Vitouš, J., Macíček, O., Krátká, L., Dražanová, E., & Starčuk, Z. (2025) · Magnetic Resonance in Medicine · doi:10.1002/mrm.30446 · Cited by 3 · see citing works
Targeted Delivery of Salusin‐α Into Rabbit Carotid Arterial Endothelium Using SonoVue
Wang, Y., Luo, M., Mao, X., Shi, X., & Liu, X. (2021) · Journal of Ultrasound in Medicine · doi:10.1002/jum.15714 · Cited by 2 · see citing works
Brain barriers and brain fluid research in 2016: advances, challenges and controversies
Keep, R. F., Jones, H. C., & Drewes, L. R. (2017) · Fluids and Barriers of the CNS · doi:10.1186/s12987-017-0052-7 · Cited by 2 · see citing works
Karakatsani, M. E. (2020) · doi:10.7916/d8-gvqg-2009
Self-citationMcMahon, D., & Hynynen, K. (2022) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-030-88773-5_19
Mondou, P., Pagé, G., Cornu, C., Morisset, C., Djaballah, E., Fayard, A., Lecourtois, S., Gay, M., Roustan, M., Flament, J., et al. (2025) · Physics in Medicine and Biology · doi:10.1088/1361-6560/addf0c
Modulating cerebrospinal fluid flow by magnetohydrodynamic force
Lori, M. S., Maroufi, S. F., Bijarchi, M. A., Luciano, M. G., Habibi, Z., & Cheng, J. (2025) · European Journal of Mechanics - B/Fluids · doi:10.1016/j.euromechflu.2025.204424 · Cited by 1 · see citing works
- Authors
- Samiotaki, G., Karakatsani, M. E., Buch, A., Papadopoulos, S., Wu, S. Y., Jambawalikar, S., & Konofagou, E. E.
- Affiliations
- Columbia University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Karakatsani, Maria Eleni
- ORCID
- Venue
- Magnetic Resonance Imaging
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 37
- Pages
- 273-281
- ISSN
- 0730-725X (ISSN-L)
- PMC
- PMC5316348
- OpenAlex
- W2558991790
- Cited by
- 35
- References
- 24
- Citations by year
- 2025: 6 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 2
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Magnetic Resonance Imaging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG038961)
- National Institute of Biomedical Imaging and Bioengineering (R01EB009041)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- focused ultrasound, blood-brain barrier opening, microbubbles, pharmacokinetics, drug delivery, non-human primates, gadolinium, acoustic pressure, brain permeability
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Contrast Media, Image Enhancement, Macaca mulatta, Male, Ultrasonics, Drug Delivery Systems, Gadolinium DTPA, Models, Animal, Microbubbles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
