Skip to main content
banner image
No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
The full text of this article is not currently available.
1.K. Hynynen and F. A. Jolesz, “Demonstration of potential noninvasive ultrasound brain therapy through an intact skull,” Ultrasound Med. Biol. 24(2), 275283 (1998).
2.G. T. Clement and K. Hynynen, “A non-invasive method for focusing ultrasound through the human skull,” Phys. Med. Biol. 47(8), 12191236 (2002).
3.N. McDannold, G. T. Clement, P. Black, F. Jolesz, and K. Hynynen, “Transcranial magnetic resonance imaging–guided focused ultrasound surgery of brain tumors: Initial findings in 3 patients,” Neurosurgery 66(2), 323332 (2010).
4.E. Martin, D. Jeanmonod, A. Morel, E. Zadicario, and B. Werner, “High-intensity focused ultrasound for noninvasive functional neurosurgery,” Ann. Neurol. 66(6), 858861 (2009).
5.D. Jeanmonod, B. Werner, A. Morel, L. Michels, E. Zadicario, G. Schiff, and E. Martin, “Transcranial magnetic resonance imaging–guided focused ultrasound: Noninvasive central lateral thalamotomy for chronic neuropathic pain,” Neurosurg. Focus 32(1), E1 (2011).
6.W. J. Elias, D. Huss, T. Voss, J. Loomba, M. Khaled, E. Zadicario, R. C. Frysinger, S. A. Sperling, S. Wylie, S. J. Monteith, J. Druzgal, B. B. Shah, M. Harrison, and M. Wintermark, “A pilot study of focused ultrasound thalamotomy for essential tremor,” N. Engl. J. Med. 369(7), 640648 (2013).
7.K. Hynynen, G. T. Clement, N. McDannold, N. Vykhodtseva, R. King, P. J. White, S. Vitek, and F. A. Jolesz, “500-element ultrasound phased array system for noninvasive focal surgery of the brain: A preliminary rabbit study with ex vivo human skulls,” Magn. Reson. Med. 52(1), 100107 (2004).
8.G. T. Clement, J. Sun, T. Giesecke, and K. Hynynen, “A hemisphere array for non-invasive ultrasound brain therapy and surgery,” Phys. Med. Biol. 45(12), 37073719 (2000).
9.J. Sun and K. Hynynen, “The potential of transskull ultrasound therapy and surgery using the maximum available skull surface area,” J. Acoust. Soc. Am. 105(4), 25192527 (1999).
10.K. Hynynen, N. McDannold, G. Clement, F. A. Jolesz, E. Zadicario, R. Killiany, T. Moore, and D. Rosen, “Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain—A primate study,” Eur. J. Radiol. 59(2), 149156 (2006).
11.A. Pulkkinen, Y. Huang, J. Song, and K. Hynynen, “Simulations and measurements of transcranial low-frequency ultrasound therapy: Skull-base heating and effective area of treatment,” Phys. Med. Biol. 56(15), 46614683 (2011).
12.P. J. White, G. T. Clement, and K. Hynynen, “Longitudinal and shear mode ultrasound propagation in human skull bone,” Ultrasound Med. Biol. 32(7), 10851096 (2006).
13.J. Song, A. Pulkkinen, Y. Huang, and K. Hynynen, “Investigation of standing-wave formation in a human skull for a clinical prototype of a large-aperture, transcranial MR-guided focused ultrasound (MRgFUS) phased array: An experimental and simulation study,” IEEE Trans. Biomed. Eng. 59(2), 435444 (2012).
14.C. W. Burke, A. L. Klibanov, J. P. Sheehan, and R. J. Price, “Inhibition of glioma growth by microbubble activation in a subcutaneous model using low duty cycle ultrasound without significant heating,” J. Neurosurg. 114(6), 16541661 (2011).
15.Y. Huang, N. I. Vykhodtseva, and K. Hynynen, “Creating brain lesions with low-intensity focused ultrasound with microbubbles: A rat study at half a megahertz,” Ultrasound Med. Biol. 39(8), 14201428 (2013).
16.N. J. McDannold, N. I. Vykhodtseva, and K. Hynynen, “Microbubble contrast agent with focused ultrasound to create brain lesions at low power levels: MR imaging and histologic study in rabbits,” Radiology 241(1), 95106 (2006).
17.N. McDannold, Y.-Z. Zhang, C. Power, F. Jolesz, and N. Vykhodtseva, “Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function,” J. Neurosurg. 119(5), 12081220 (2013).
18.C. D. Arvanitis, M. S. Livingstone, N. Vykhodtseva, and N. McDannold, “Controlled ultrasound-induced blood–brain barrier disruption using passive acoustic emissions monitoring,” PLoS One 7(9), e45783 (2012).
19.M. Aryal, C. D. Arvanitis, P. M. Alexander, and N. McDannold, “Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system,” Adv. Drug Delivery Rev. 72, 94109 (2014).
20.Y.-S. Tung, F. Marquet, T. Teichert, V. Ferrera, and E. E. Konofagou, “Feasibility of noninvasive cavitation-guided blood–brain barrier opening using focused ultrasound and microbubbles in nonhuman primates,” Appl. Phys. Lett. 98(16), 163704 (2011).
21.N. McDannold, N. Vykhodtseva, and K. Hynynen, “Targeted disruption of the blood–brain barrier with focused ultrasound: Association with cavitation activity,” Phys. Med. Biol. 51(4), 793807 (2006).
22.C. D. Arvanitis, M. S. Livingstone, and N. McDannold, “Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain,” Phys. Med. Biol. 58(14), 47494761 (2013).
23.C. D. Arvanitis, N. Vykhodtseva, F. Jolesz, M. Livingstone, and N. McDannold, “Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model,” J. Neurosurgery 9, 110 (2015) [Epub ahead of print].
24.M. Gyöngy and C.-C. Coussios, “Passive cavitation mapping for localization and tracking of bubble dynamics,” J. Acoust. Soc. Am. 128(4), EL175EL180 (2010).
25.V. A. Salgaonkar, S. Datta, C. K. Holland, and T. D. Mast, “Passive cavitation imaging with ultrasound arrays,” J. Acoust. Soc. Am. 126(6), 30713083 (2009).
26.K. J. Haworth, T. D. Mast, K. Radhakrishnan, M. T. Burgess, J. A. Kopechek, S.-L. Huang, D. D. McPherson, and C. K. Holland, “Passive imaging with pulsed ultrasound insonations,” J. Acoust. Soc. Am. 132(1), 544553 (2012).
27.C. Coviello, R. Kozick, J. Choi, M. Gyöngy, C. Jensen, P. P. Smith, and C.-C. Coussios, “Passive acoustic mapping utilizing optimal beamforming in ultrasound therapy monitoring,” J. Acoust. Soc. Am. 137(5), 25732585 (2015).
28.M. A. O’Reilly, R. M. Jones, and K. Hynynen, “Three-dimensional transcranial ultrasound imaging of microbubble clouds using a sparse hemispherical array,” IEEE Trans. Biomed. Eng. 61(4), 12851294 (2014).
29.R. M. Jones, M. A. O’Reilly, and K. Hynynen, “Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections,” Med. Phys. 42(7), 43854400 (2015).
30.B. E. Treeby and B. T. Cox, “k-wave: matlab toolbox for the simulation and reconstruction of photoacoustic wave fields,” J. Biomed. Opt. 15(2), 021314 (2010).
31.Q. H. Liu, “The pseudospectral time-domain (PSTD) algorithm for acoustic waves in absorptive media,” IEEE Trans. Ultrason., Ferroelectr., Freq. Control 45(4), 10441055 (1998).
32.Y. Jing, F. C. Meral, and G. T. Clement, “Time-reversal transcranial ultrasound beam focusing using a k-space method,” Phys. Med. Biol. 57(4), 901917 (2012).
33.M. Tabei, T. D. Mast, and R. C. Waag, “A k-space method for coupled first-order acoustic propagation equations,” J. Acoust. Soc. Am. 111(1), 5363 (2002).
34.B. E. Treeby, J. Jaros, A. P. Rendell, and B. T. Cox, “Modeling nonlinear ultrasound propagation in heterogeneous media with power law absorption using a k-space pseudospectral method,” J. Acoust. Soc. Am. 131(6), 43244336 (2012).
35.K. Firouzi, B. T. Cox, B. E. Treeby, and N. Saffari, “A first-order k-space model for elastic wave propagation in heterogeneous media,” J. Acoust. Soc. Am. 132(3), 12711283 (2012).
36.R. G. Holt and L. A. Crum, “Acoustically forced oscillations of air bubbles in water: Experimental results,” J. Acoust. Soc. Am. 91(4), 19241932 (1992).
37.C. C. Coussios, C. H. Farny, G. T. Haar, and R. A. Roy, “Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU),” Int. J. Hyperthermia 23(2), 105120 (2007).
38.W.-S. Chen, A. A. Brayman, T. J. Matula, and L. A. Crum, “Inertial cavitation dose and hemolysis produced in vitro with or without Optison®,” Ultrasound Med. Biol. 29(5), 725737 (2003).
39.B. E. Treeby and B. T. Cox, “Modeling power law absorption and dispersion in viscoelastic solids using a split-field and the fractional Laplacian,” J. Acoust. Soc. Am. 136(4), 14991510 (2014).
40.A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D slicer as an image computing platform for the quantitative imaging network,” Magn. Reson. Imaging 30(9), 13231341 (2012).
41.J. F. Aubry, M. Tanter, M. Pernot, J. L. Thomas, and M. Fink, “Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans,” J. Acoust. Soc. Am. 113(1), 8493 (2003).
42.F. Marquet, M. Pernot, J.-F. Aubry, G. Montaldo, L. Marsac, M. Tanter, and M. Fink, “Non-invasive transcranial ultrasound therapy based on a 3D CT scan: Protocol validation and in vitro results,” Phys. Med. Biol. 54(9), 25972613 (2009).
43.M. Greenspan and C. Tschiegg, “Speed of sound in water by a direct method,” J. Res. Natl. Bur. Stand. 59(4), 249254 (1957).
44.C. W. Connor and K. Hynynen, “Patterns of thermal deposition in the skull during transcranial focused ultrasound surgery,” IEEE Trans. Biomed. Eng. 51(10), 16931706 (2004).
45.F. A. Duck, Physical Properties of Tissue: A Comprehensive Reference Book (Academic, San Diego, London, 1990).
46.Tissue Substitutes, Phantoms, and Computational Modelling in Medical Ultrasound, International Commission on Radiation Units and Measurements, 1998.
47.M. Born and E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference, and Diffraction of Light (Pergamon, Oxford, UK, 1959).
48.H. T. O’Neil, “Theory of focusing radiators,” Acoust. Soc. Am. J. 21, 516526 (1949).
49.P. P. Lele, “Effects of ultrasound on ‘solid’ mammalian tissues and tumors in vivo,” inUltrasound, edited by M. H. Repacholi, M. Grandolfo, and A. Rindi (Springer, New York, NY, 1987), pp. 275306.
50.J. White, G. T. Clement, and K. Hynynen, “Transcranial ultrasound focus reconstruction with phase and amplitude correction,” IEEE Trans. Ultrason., Ferroelectr., Freq. Control 52(9), 15181522 (2005).
51.T. D. Mast, “Empirical relationships between acoustic parameters in human soft tissues,” Acoust. Res. Lett. Online 1(2), 3742 (2000).
52.N. McDannold, C. D. Arvanitis, N. Vykhodtseva, and M. S. Livingstone, “Temporary disruption of the blood–brain barrier by use of ultrasound and microbubbles: Safety and efficacy evaluation in rhesus macaques,” Cancer Res. 72(14), 36523663 (2012).
53.F. Y. Yang, W. M. Fu, W. S. Chen, W. L. Yeh, and W. L. Lin, “Quantitative evaluation of the use of microbubbles with transcranial focused ultrasound on blood–brain-barrier disruption,” Ultrason. Sonochem. 15(4), 636643 (2008).
54.R. Chopra, N. Vykhodtseva, and K. Hynynen, “Influence of exposure time and pressure amplitude on blood− brain-barrier opening using transcranial ultrasound exposures,” ACS Chem. Neurosci. 1(5), 391398 (2010).
55.L. C. Moyer, K. F. Timbie, P. S. Sheeran, R. J. Price, G. W. Miller, and P. A. Dayton, “High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles,” J. Ther. Ultrasound 3(7), 19 (2015).
56.E. Sassaroli and K. Hynynen, “Cavitation threshold of microbubbles in gel tunnels by focused ultrasound,” Ultrasound Med. Biol. 33(10), 16511660 (2007).
57.E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood–brain barrier opening,” J. Cereb. Blood Flow Metab. 31(9), 18521862 (2011).

Data & Media loading...


Article metrics loading...



Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low-duty-cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood–brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects.

The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI-guided FUS system. Low-duty-cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models.

The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive cavitation detector was used to measure the inertial cavitation threshold and to determine the pressure amplitude to use for ablation. Simulations of the detector’s acoustic field suggest that its maximum sensitivity was in the lower part of the main beam, which may have led to excessive exposure levels in the experiments that may have contributed to damage in the prefocal area.

Overall, these results suggest that case-specific full wave simulations before the procedure can be useful to predict the focal and the prefocal side lobes and the extent of the resulting bioeffects produced by nonthermal ablation. Such simulations can also be used to optimally position passive cavitation detectors. The disagreement between the simulations and the experiments in the postfocal region may have been due to shielding of the ultrasound field due to microbubble activity in the focal region. Future efforts should include the effects of microbubble activity and vascularization on the pressure field.


Full text loading...


Access Key

  • FFree Content
  • OAOpen Access Content
  • SSubscribed Content
  • TFree Trial Content
752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd