Microbubbles as a novel contrast agent for brain MRI
Abstract
Gas-filled microbubbles have the potential to become a unique MR contrast agent due to their magnetic susceptibility effect, biocompatibility and localized manipulation via ultrasound cavitation. In this study, two types of microbubbles, custom-made albumin-coated microbubbles (A-MB) and a commercially available lipid-based clinical ultrasound contrast agent (SonoVue), were investigated with in vivo dynamic brain MRI in Sprague-Dawley rats at 7 T. Microbubble suspensions (A-MB: 0.2 mL of approximately 4% volume fraction; SonoVue: 0.2 mL of approximately 3.5% volume fraction) were injected intravenously. Transverse relaxation rate enhancements (DeltaR(2)(*)) of 2.49+/-1.00 s(-1) for A-MB and 2.41+/-1.18 s(-1) for SonoVue were observed in the brain (N=5). Brain DeltaR(2)(*) maps were computed, yielding results similar to the cerebral blood volume maps obtained with a common MR blood pool contrast agent. Microbubble suspension DeltaR(2)(*) was measured for different volume fractions. These results indicate that gas-filled microbubbles can serve as an intravascular contrast agent for brain MRI at high field. Such capability has the potential to lead to real-time MRI guidance in various microbubble-based drug delivery and therapeutic applications in the central nervous system.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Automated Image Registration: I. General Methods and Intrasubject, Intramodality Validation
Woods, R. P., Grafton, S. T., Holmes, C. J., Cherry, S. R., & Mazziotta, J. C. (1998) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199801000-00027 · Cited by 1,707 · see citing works
Microscopic susceptibility variation and transverse relaxation: Theory and experiment
Weisskoff, R. M., Zuo, C. S., Boxerman, J. L., & Rosen, B. R. (1994) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910310605 · Cited by 714 · see citing works
Rempp, K., Brix, G., Wenz, F. K., Becker, C. R., Gückel, F., & Lorenz, W. (1994) · Radiology · doi:10.1148/radiology.193.3.7972800 · Cited by 638 · see citing works
Sheikov, N. A., McDannold, N. J., Vykhodtseva, N. I., Jolesz, F. A., & Hynynen, K. (2004) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2004.04.010 · Cited by 619 · see citing works
Functional cerebral imaging by susceptibility‐contrast NMR
Belliveau, J. W., Rosen, B. R., Kantor, H. L., Rzedzian, R. R., Kennedy, D. N., McKinstry, R. C., Vevea, J. M., Cohen, M. S., Pykett, I. L., & Brady, T. J. (1990) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910140311 · Cited by 566 · see citing works
Mr perfusion studies with t1‐weighted echo planar imaging
Kwong, K. K., Chesler, D. A., Weisskoff, R. M., Donahue, K. M., Davis, T. L., Østergaard, L., Campbell, T. A., & Rosen, B. R. (1995) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910340613 · Cited by 475 · see citing works
Local Delivery of Plasmid DNA Into Rat Carotid Artery Using Ultrasound
Taniyama, Y., Tachibana, K., Hiraoka, K., et al. (2002) · Circulation · doi:10.1161/hc1002.105228 · Cited by 470 · see citing works
Plasma membrane poration induced by ultrasound exposure: Implication for drug delivery
Mehier-Humbert, S., Bettinger, T., Yan, F., et al. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.01.007 · Cited by 360 · see citing works
Bekeredjian, R., Chen, S., Frenkel, P. A., Grayburn, P. A., & Shohet, R. V. (2003) · Circulation · doi:10.1161/01.cir.0000084535.35435.ae · Cited by 321 · see citing works
Encapsulated ultrasound microbubbles: Therapeutic application in drug/gene delivery
Liu, Y., Miyoshi, H., & Nakamura, M. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.05.018 · Cited by 318 · see citing works
Local drug and gene delivery through microbubbles
Unger, E. C., Hersh, E. M., Vannan, M. A., Matsunaga, T. O., & McCreery, T. P. (2001) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2001.26443 · Cited by 307 · see citing works
Contrast agents and cerebral hemodynamics
Rosen, B. R., Belliveau, J. W., Buchbinder, B. R., McKinstry, R. C., Porkka, L., Kennedy, D. N., NEUDER, M., Fisel, C. R., Aronen, H. J., Kwong, K. K., et al. (1991) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910190216 · Cited by 287 · see citing works
Enochs, W. S., Harsh, G. R., Hochberg, F. H., & Weissleder, R. (1999) · Journal of Magnetic Resonance Imaging · doi:10.1002/(sici)1522-2586(199902)9:2 · Cited by 247 · see citing works
High-speed optical observations of contrast agent destruction
Bouakaz, A., Versluis, M., & de Jong, N. (2005) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2004.12.004 · Cited by 190 · see citing works
Kaneko, Y., Maruyama, T., Takegami, K., et al. (2005) · European Radiology · doi:10.1007/s00330-005-2663-7 · Cited by 178 · see citing works
Interfacial Polygonal Nanopatterning of Stable Microbubbles
Dressaire, E., Bee, R. D., Bell, D. C., et al. (2008) · Science · doi:10.1126/science.1154601 · Cited by 151 · see citing works
Intracranial Clot Lysis With Intravenous Microbubbles and Transcranial Ultrasound in Swine
Culp, W. C., Porter, T. R., Lowery, J. D., et al. (2004) · Stroke · doi:10.1161/01.str.0000140890.86779.79 · Cited by 148 · see citing works
Ultrasound in the treatment of ischaemic stroke
Daffertshofer, M., & Hennerici, M. G. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00380-6 · Cited by 111 · see citing works
Hauff, P., Seemann, S., Reszka, R. C., et al. (2005) · Radiology · doi:10.1148/radiol.2362040870 · Cited by 110 · see citing works
Shimamura, M., Sato, N., Taniyama, Y., Yamamoto, S., Endoh, M., Kurinami, H., Aoki, M., Ogihara, T., Kaneda, Y., & Morishita, R. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302323 · Cited by 100 · see citing works
Bjørnerud, A., Johansson, L. O. M., Briley-Saebo, K. C., et al. (2002) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10066 · Cited by 97 · see citing works
Imaging of angiogenesis using Cadence™ contrast pulse sequencing and targeted contrast agents
Stieger‐Vanegas, S. M., Dayton, P. A., Borden, M. A., et al. (2008) · Contrast Media & Molecular Imaging · doi:10.1002/cmmi.224 · Cited by 87 · see citing works
Sonoporation, anti-cancer drug and antibody delivery using ultrasound
Wu, J., Pepe, J., & Rincón, M. (2006) · Ultrasonics · doi:10.1016/j.ultras.2006.06.033 · Cited by 86 · see citing works
Wu, E. X., Tang, H., & Jensen, J. H. (2004) · NMR in Biomedicine · doi:10.1002/nbm.923 · Cited by 79 · see citing works
Self-citationvan Bruggen, N., Busch, E. W., Palmer, J. T., Williams, S., & de Crespigny, A. J. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199811000-00003 · Cited by 77 · see citing works
Wu, E. X., Tang, H., Wong, K., et al. (2003) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.10426 · Cited by 49 · see citing works
Self-citationHigh‐resolution in vivo CBV mapping with MRI in wild‐type mice
Wu, E. X., Wong, K., Andrassy, M., & Tang, H. (2003) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10425 · Cited by 47 · see citing works
Self-citationHigh‐resolution MR imaging of mouse brain microvasculature using the relaxation rate shift index Q
Wu, E. X., Tang, H., & Jensen, J. H. (2004) · NMR in Biomedicine · doi:10.1002/nbm.921 · Cited by 46 · see citing works
Self-citationMicrobubbles as novel pressure‐sensitive MR contrast agents
Alexander, A. L., McCreery, T. P., Barrette, T. R., et al. (1996) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910350603 · Cited by 40 · see citing works
Regional cerebral blood volume reduction in transgenic mutant APP (V717F, K670N/M671L) mice
Wu, E. X., Tang, H., Asai, T., & Yan, S. D. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.05.004 · Cited by 38 · see citing works
Self-citationOn the parameters affecting the sensitivity of MR measures of pressure with microbubbles
Dharmakumar, R., Plewes, D. B., & Wright, G. A. (2002) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10075 · Cited by 32 · see citing works
In vivo study of microbubbles as an MR susceptibility contrast agent
Wong, K., Huang, I., Kim, Y. R., et al. (2004) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20181 · Cited by 29 · see citing works
Guio, F. D., Benoit-Cattin, H., & Davenel, A. (2008) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-008-0119-1 · Cited by 18 · see citing works
Air Microbubbles as MR Susceptibility Contrast Agent at 1.5 Tesla
Ueguchi, T., Tanaka, Y., Hamada, S., et al. (2006) · Magnetic Resonance in Medical Sciences · doi:10.2463/mrms.5.147 · Cited by 14 · see citing works
Estimated Functional Diameter of Alveolar Septal Microvessels at the Zone I‐II Border
Conhai, R. L., & Rodenkirch, L. A. (1997) · Microcirculation · doi:10.3109/10739689709148317 · Cited by 11 · see citing works
Perfusion/Diffusion Quantitation with Magnetic Resonance Imaging
Pickens, D. R. (1992) · Investigative Radiology · doi:10.1097/00004424-199212002-00003 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications
Dadfar, S. M., Roemhild, K., Drude, N. I., von Stillfried, S., Knüchel, R., Kiessling, F., & Lammers, T. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.01.005 · Cited by 1,181 · see citing works
- Authors
- Cheung, J. S., Chow, A. M., Guo, H., & Wu, E. X.
- Affiliations
- University of Hong Kong (HK)
- ORCID
- Guo, Hua
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 46
- Issue
- 3
- Pages
- 658-664
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2083313327
- Cited by
- 36
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- University of Hong Kong
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Keywords
- microbubbles, MRI contrast agents, brain MRI, SonoVue, ultrasound contrast agents, magnetic susceptibility, cerebral blood volume, high-field MRI, MRI-guided therapy
- MeSH terms
- Animals, Brain, Contrast Media, Image Enhancement, Phospholipids, Sensitivity and Specificity, Sulfur Hexafluoride, Reproducibility of Results, Rats, Sprague-Dawley, Microbubbles, Rats
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
