, Volume 16, Issue 1, pp 88–99 | Cite as

Focused Ultrasound for Neuromodulation

  • David P DarrowEmail author


For more than 70 years, the promise of noninvasive neuromodulation using focused ultrasound has been growing while diagnostic ultrasound established itself as a foundation of clinical imaging. Significant technical challenges have been overcome to allow transcranial focused ultrasound to deliver spatially restricted energy into the nervous system at a wide range of intensities. High-intensity focused ultrasound produces reliable permanent lesions within the brain, and low-intensity focused ultrasound has been reported to both excite and inhibit neural activity reversibly. Despite intense interest in this promising new platform for noninvasive, highly focused neuromodulation, the underlying mechanism remains elusive, though recent studies provide further insight. Despite the barriers, the potential of focused ultrasound to deliver a range of permanent and reversible neuromodulation with seamless translation from bench to the bedside warrants unparalleled attention and scientific investment. Focused ultrasound boasts a number of key features such as multimodal compatibility, submillimeter steerable focusing, multifocal, high temporal resolution, coregistration, and the ability to monitor delivered therapy and temperatures in real time. Despite the technical complexity, the future of noninvasive focused ultrasound for neuromodulation as a neuroscience and clinical platform remains bright.

Key Words

Focused ultrasound LIFU HIFU neuromodulation 


Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Supplementary material

13311_2018_691_MOESM1_ESM.pdf (510 kb)
ESM 1 (PDF 510 kb)


  1. 1.
    O’Brien WD Jr. Ultrasound-biophysics mechanisms. Prog. Biophys. Mol. Biol. 2007;93:212–255.Google Scholar
  2. 2.
    Chan V, Perlas A. Basics of Ultrasound Imaging. In: Narouze SN, editor. Atlas of Ultrasound-Guided Procedures in Interventional Pain Management. New York, NY: Springer New York; 2011. p. 13–19.Google Scholar
  3. 3.
    Pinton G, Aubry J-F, Bossy E, et al. Attenuation, scattering, and absorption of ultrasound in the skull bone. Med. Phys. 2012;39:299–307.Google Scholar
  4. 4.
    Harary M, Segar DJ, Huang KT, et al. Focused ultrasound in neurosurgery: a historical perspective. Neurosurg. Focus. 2018;44:E2.Google Scholar
  5. 5.
    Duck FA. Nonlinear acoustics in diagnostic ultrasound. Ultrasound Med. Biol. 2002;28:1–18.Google Scholar
  6. 6.
    Liu D, Casper A, Haritonova A, et al. Adaptive lesion formation using dual mode ultrasound array system. AIP Conf. Proc. 2017;1821:060003.Google Scholar
  7. 7.
    Newman PG, Rozycki GS. The history of ultrasound. Surg. Clin. North Am. 1998;78:179–195.Google Scholar
  8. 8.
    Strowitzki M, Moringlane JR, Steudel W. Ultrasound-based navigation during intracranial burr hole procedures: experience in a series of 100 cases. Surg. Neurol. 2000;54:134–144.Google Scholar
  9. 9.
    Meyer RA. History of ultrasound in cardiology. J. Ultrasound Med. 2004;23:1–11.Google Scholar
  10. 10.
    Sun XL, Yan JP, Li YF, et al. Multi-frequency ultrasound transducers for medical applications: a survey. International Journal of Intelligent Robotics and Applications [Internet]. 2018.
  11. 11.
    Shankar H, Pagel PS. Potential Adverse Ultrasound-related Biological EffectsA Critical Review. Anesthesiology. 2011;115:1109–1124.Google Scholar
  12. 12.
    Naor O, Krupa S, Shoham S. Ultrasonic neuromodulation. J. Neural Eng. 2016;13:031003.Google Scholar
  13. 13.
    Dalecki D. Mechanical bioeffects of ultrasound. Annu. Rev. Biomed. Eng. 2004;6:229–248.Google Scholar
  14. 14.
    Krasovitski B, Frenkel V, Shoham S, et al. Intramembrane cavitation as a unifying mechanism for ultrasound-induced bioeffects. Proc. Natl. Acad. Sci. U. S. A. 2011;108:3258–3263.Google Scholar
  15. 15.
    Sarvazyan AP, Rudenko OV, Nyborg WL. Biomedical applications of radiation force of ultrasound: historical roots and physical basis. Ultrasound Med. Biol. 2010;36:1379–1394.Google Scholar
  16. 16.
    Baker KG, Robertson VJ, Duck FA. A review of therapeutic ultrasound: biophysical effects. Phys. Ther. 2001;81:1351–1358.Google Scholar
  17. 17.
    Rossmanna C, Haemmerich D. Review of temperature dependence of thermal properties, dielectric properties, and perfusion of biological tissues at hyperthermic and ablation temperatures. Crit. Rev. Biomed. Eng. 2014;42:467–492.Google Scholar
  18. 18.
    Wojcik G, Mould J, Abboud N, et al. Nonlinear modeling of therapeutic ultrasound. 1995 IEEE Ultrasonics Symposium. Proceedings. An International Symposium.; 1995. p. 1617–1622 vol.2.
  19. 19.
    Pinton G, Pernot M, Bossy E, et al. Mechanisms of attenuation and heating dissipation of ultrasound in the skull bone: Comparison between simulation models and experiments. 2010 IEEE International Ultrasonics Symposium. 2010. p. 225–228.Google Scholar
  20. 20.
    Seip R, Ebbini ES. Noninvasive estimation of tissue temperature response to heating fields using diagnostic ultrasound. IEEE Trans. Biomed. Eng. 1995;42:828–839.Google Scholar
  21. 21.
    Krishna V, Sammartino F, Rezai A. A Review of the Current Therapies, Challenges, and Future Directions of Transcranial Focused Ultrasound Technology: Advances in Diagnosis and Treatment. JAMA Neurol. 2018;75:246–254.Google Scholar
  22. 22.
    Smith NB, Webb AG, Ellis DS, et al. Experimental verification of theoretical in vivo ultrasound heating using cobalt detected magnetic resonance. IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 1995;42:489–491.Google Scholar
  23. 23.
    Draper DO, Castel JC, Castel D. Rate of temperature increase in human muscle during 1 MHz and 3 MHz continuous ultrasound. J. Orthop. Sports Phys. Ther. 1995;22:142–150.Google Scholar
  24. 24.
    Ng A, Swanevelder J. Resolution in ultrasound imaging. Contin Educ Anaesth Crit Care Pain. 2011;11:186–192.Google Scholar
  25. 25.
    Pennes HH. Analysis of tissue and arterial blood temperatures in the resting human forearm. J. Appl. Physiol. 1948;1:93–122.Google Scholar
  26. 26.
    Evans KD, Weiss B, Knopp M. High-Intensity Focused Ultrasound (HIFU) for Specific Therapeutic Treatments: A Literature Review. J. Diagn. Med. Sonogr. 2007;23:319–327.Google Scholar
  27. 27.
    Elias WJ, Huss D, Voss T, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N. Engl. J. Med. 2013;369:640–648.Google Scholar
  28. 28.
    Ikeda T, Yoshizawa S, Koizumi N, et al. Focused Ultrasound and Lithotripsy. Adv. Exp. Med. Biol. 2016;880:113–129.Google Scholar
  29. 29.
    Rinaldi PC, Jones JP, Reines F, et al. Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation. Brain Res. 1991;558:36–42.Google Scholar
  30. 30.
    Tufail Y, Matyushov A, Baldwin N, et al. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron. 2010;66:681–694.Google Scholar
  31. 31.
    Wahab RA, Choi M, Liu Y, et al. Mechanical bioeffects of pulsed high intensity focused ultrasound on a simple neural model: Bioeffects of pulsed ultrasound on nerves. Med. Phys. 2012;39:4274–4283.Google Scholar
  32. 32.
    Baek H, Pahk KJ, Kim H. A review of low-intensity focused ultrasound for neuromodulation. Biomed. Eng. Lett. 2017;7:135–142.Google Scholar
  33. 33.
    Barnett SB, Ter Haar GR, Ziskin MC, et al. International recommendations and guidelines for the safe use of diagnostic ultrasound in medicine. Ultrasound Med. Biol. 2000;26:355–366.Google Scholar
  34. 34.
    Nelson TR, Fowlkes JB, Abramowicz JS, et al. Ultrasound biosafety considerations for the practicing sonographer and sonologist. J. Ultrasound Med. 2009;28:139–150.Google Scholar
  35. 35.
    Dickson JA, Calderwood SK. Temperature range and selective sensitivity of tumors to hyperthermia: a critical review. Ann. N. Y. Acad. Sci. 1980;335:180–205.Google Scholar
  36. 36.
    Kyriakou Z, Corral-Baques MI, Amat A, et al. HIFU-induced cavitation and heating in ex vivo porcine subcutaneous fat. Ultrasound Med. Biol. 2011;37:568–579.Google Scholar
  37. 37.
    Tyler WJ, Lani SW, Hwang GM. Ultrasonic modulation of neural circuit activity. Curr. Opin. Neurobiol. 2018;50:222–231.Google Scholar
  38. 38.
    Neppiras EA. Acoustic cavitation series: part one: Acoustic cavitation: an introduction. Ultrasonics. 1984;22:25–28.Google Scholar
  39. 39.
    Izadifar Z, Babyn P, Chapman D. Mechanical and Biological Effects of Ultrasound: A Review of Present Knowledge. Ultrasound in Medicine and Biology. 2017;43:1085–1104.Google Scholar
  40. 40.
    Church CC. Spontaneous homogeneous nucleation, inertial cavitation and the safety of diagnostic ultrasound. Ultrasound Med. Biol. 2002;28:1349–1364.Google Scholar
  41. 41.
    Holland CK, Deng CX, Apfel RE, et al. Direct evidence of cavitation in vivo from diagnostic ultrasound. Ultrasound Med. Biol. 1996;22:917–925.Google Scholar
  42. 42.
    Abbott NJ, Rönnbäck L, Hansson E. Astrocyte–endothelial interactions at the blood–brain barrier. Nat. Rev. Neurosci. 2006;7:41.Google Scholar
  43. 43.
    Bakay L, Ballantine HT Jr, Hueter TF, et al. Ultrasonically produced changes in the blood-brain barrier. AMA Arch. Neurol. Psychiatry. 1956;76:457–467.Google Scholar
  44. 44.
    Patrick JT, Nolting MN, Goss SA, et al. Ultrasound and the blood-brain barrier. Adv. Exp. Med. Biol. 1990;267:369–381.Google Scholar
  45. 45.
    Ballantine HT Jr, Bell E, Manlapaz J. Progress and problems in the neurological applications of focused ultrasound. J. Neurosurg. 1960;17:858–876.Google Scholar
  46. 46.
    Hynynen K, McDannold N, Vykhodtseva N, et al. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology. 2001;220:640–646.Google Scholar
  47. 47.
    Yang F-Y, Lin Y-S, Kang K-H, et al. Reversible blood–brain barrier disruption by repeated transcranial focused ultrasound allows enhanced extravasation. J. Control. Release. 2011;150:111–116.Google Scholar
  48. 48.
    Airan RD, Meyer RA, Ellens NPK, et al. Noninvasive Targeted Transcranial Neuromodulation via Focused Ultrasound Gated Drug Release from Nanoemulsions. Nano Lett. 2017;17:652–659.Google Scholar
  49. 49.
    Downs ME, Buch A, Karakatsani ME, et al. Blood-Brain Barrier Opening in Behaving Non-Human Primates via Focused Ultrasound with Systemically Administered Microbubbles. Sci. Rep. 2015;5:15076.Google Scholar
  50. 50.
    Wang S, Kugelman T, Buch A, et al. Non-invasive, Focused Ultrasound-Facilitated Gene Delivery for Optogenetics, Sci. Rep. 2017;7:39955.Google Scholar
  51. 51.
    Mead B, Kim N, Negron K, et al. Intersections of neuromodulation, focused ultrasound, and gene delivery with brain-penetrating nanoparticles. J. Acoust. Soc. Am. 2017;142:2669–2669.Google Scholar
  52. 52.
    Rudenko OV, Sarvazyan AP, Emelianov SY. Acoustic radiation force and streaming induced by focused nonlinear ultrasound in a dissipative medium. J. Acoust. Soc. Am. 1996;99:2791–2798.Google Scholar
  53. 53.
    Tyler WJ, Tufail Y, Finsterwald M, et al. Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound. PLoS One. 2008;3:e3511.Google Scholar
  54. 54.
    Kubanek J, Shi J, Marsh J, et al. Ultrasound modulates ion channel currents. Sci. Rep. 2016;6:24170.Google Scholar
  55. 55.
    Kubanek J, Shukla P, Das A, et al. Ultrasound Elicits Behavioral Responses through Mechanical Effects on Neurons and Ion Channels in a Simple Nervous System. J. Neurosci. 2018;38:3081–3091.Google Scholar
  56. 56.
    Duck FA. The Meaning of Thermal Index (TI) and Mechanical Index (MI) Values. BMUS Bulletin. 1997;5:36–40.Google Scholar
  57. 57.
    Humphrey VF. Nonlinear propagation in ultrasonic fields: measurements, modelling and harmonic imaging. Ultrasonics. 2000;38:267–272.Google Scholar
  58. 58.
    Zemp RJ, Tavakkoli J, Cobbold RSC. Modeling of nonlinear ultrasound propagation in tissue from array transducers. J. Acoust. Soc. Am. 2003;113:139–152.Google Scholar
  59. 59.
    Kubanek J. Neuromodulation with transcranial focused ultrasound. Neurosurg. Focus. 2018;44:E14.Google Scholar
  60. 60.
    Hand JW, Shaw A, Sadhoo N, et al. A random phased array device for delivery of high intensity focused ultrasound. Phys. Med. Biol. 2009;54:5675–5693.Google Scholar
  61. 61.
    Techavipoo U, Worasawate D, Boonleelakul W, et al. Toward Optimal Computation of Ultrasound Image Reconstruction Using CPU and GPU. Sensors [Internet]. 2016;16. Available from:
  62. 62.
    Ebbini ES, Yao H, Shrestha A. Dual-mode ultrasound phased arrays for image-guided surgery. Ultrason. Imaging. 2006;28:65–82.Google Scholar
  63. 63.
    Mueller JK, Ai L, Bansal P, et al. Numerical evaluation of the skull for human neuromodulation with transcranial focused ultrasound. J. Neural Eng. 2017;14:066012.Google Scholar
  64. 64.
    Magnin R, Rabusseau F, Salabartan F, et al. Magnetic resonance-guided motorized transcranial ultrasound system for blood-brain barrier permeabilization along arbitrary trajectories in rodents. J Ther Ultrasound. 2015;3:22.Google Scholar
  65. 65.
    Bystritsky A, Korb AS, Douglas PK, et al. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011;4:125–136.Google Scholar
  66. 66.
    Lynn JG, Zwemer RL, Chick AJ, et al. A new method for the generation and use of focused ultrasound in experimental biology. J. Gen. Physiol. 1942;26:179–193.Google Scholar
  67. 67.
    Ye G, Smith PP, Noble JA. Model-based ultrasound temperature visualization during and following HIFU exposure. Ultrasound Med. Biol. 2010;36:234–249.Google Scholar
  68. 68.
    Gyöngy M, Coussios C-C. Passive spatial mapping of inertial cavitation during HIFU exposure. IEEE Trans. Biomed. Eng. 2010;57:48–56.Google Scholar
  69. 69.
    Miller NR, Bamber JC, ter Haar GR. Imaging of temperature-induced echo strain: preliminary in vitro study to assess feasibility for guiding focused ultrasound surgery. Ultrasound Med. Biol. 2004;30:345–356.Google Scholar
  70. 70.
    Simon C, Vanbaren P, Ebbini ES. Two-dimensional temperature estimation using diagnostic ultrasound. IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 1998;45:1088–1099.Google Scholar
  71. 71.
    Yung JP, Shetty A, Elliott A, et al. Quantitative comparison of thermal dose models in normal canine brain. Med. Phys. 2010;37:5313–5321.Google Scholar
  72. 72.
    Takagi SF, Higashino S, Shibuya T, et al. The actions of ultrasound on the myelinated nerve, the spinal cord and the brain. Jpn. J. Physiol. 1960;10:183–193.Google Scholar
  73. 73.
    Tsui P-H, Wang S-H, Huang C-C. In vitro effects of ultrasound with different energies on the conduction properties of neural tissue. Ultrasonics. 2005;43:560–565.Google Scholar
  74. 74.
    Legon W, Sato TF, Opitz A, et al. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat. Neurosci. 2014;17:322–329.Google Scholar
  75. 75.
    Gulick DW, Li T, Kleim JA, et al. Comparison of Electrical and Ultrasound Neurostimulation in Rat Motor Cortex. Ultrasound Med. Biol. 2017;43:2824–2833.Google Scholar
  76. 76.
    Daniels D, Sharabi S, Last D, et al. Focused Ultrasound-Induced Suppression of Auditory Evoked Potentials in Vivo. Ultrasound Med. Biol. 2018;44:1022–1030.Google Scholar
  77. 77.
    Min B-K, Bystritsky A, Jung K-I, et al. Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. BMC Neurosci. 2011;12:23.Google Scholar
  78. 78.
    Chu P-C, Liu H-L, Lai H-Y, et al. Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening. Sci. Rep. 2015;5:15477.Google Scholar
  79. 79.
    Kim H, Park MY, Lee SD, et al. Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound. Neuroreport. 2015;26:211–215.Google Scholar
  80. 80.
    Dallapiazza RF, Timbie KF, Holmberg S, et al. Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound. J. Neurosurg. 2017;1–10.Google Scholar
  81. 81.
    Fry FJ, Ades HW, Fry WJ. Production of reversible changes in the central nervous system by ultrasound. Science. 1958;127:83–84.Google Scholar
  82. 82.
    Rezayat E, Toostani IG. A Review on Brain Stimulation Using Low Intensity Focused Ultrasound. Basic Clin Neurosci. 2016;7:187–194.Google Scholar
  83. 83.
    Dinno MA, Dyson M, Young SR, et al. The significance of membrane changes in the safe and effective use of therapeutic and diagnostic ultrasound. Phys. Med. Biol. 1989;34:1543–1552.Google Scholar
  84. 84.
    Yoo S-S, Bystritsky A, Lee J-H, et al. Focused ultrasound modulates region-specific brain activity. Neuroimage. 2011;56:1267–1275.Google Scholar
  85. 85.
    Kim H, Taghados SJ, Fischer K, et al. Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound. Ultrasound Med. Biol. 2012;38:1568–1575.Google Scholar
  86. 86.
    Wright CJ, Rothwell J, Saffari N. Ultrasonic stimulation of peripheral nervous tissue: an investigation into mechanisms. J. Phys. Conf. Ser. 2015;581:012003.Google Scholar
  87. 87.
    Buzatu S. The temperature-induced changes in membrane potential. Riv. Biol. 2009;102:199–217.Google Scholar
  88. 88.
    Borrelli MJ, Bailey KI, Dunn F. Early ultrasonic effects upon mammalian CNS structures (chemical synapses). J. Acoust. Soc. Am. 1981;69:1514–1516.Google Scholar
  89. 89.
    Juan EJ, González R, Albors G, et al. Vagus Nerve Modulation Using Focused Pulsed Ultrasound: Potential Applications and Preliminary Observations in a Rat. Int. J. Imaging Syst. Technol. 2014;24:67–71.Google Scholar
  90. 90.
    Lele PP. Effects of focused ultrasonic radiation on peripheral nerve, with observations on local heating. Exp. Neurol. 1963;8:47–83.Google Scholar
  91. 91.
    Tyler WJ. The mechanobiology of brain function. Nat. Rev. Neurosci. 2012;13:867–878.Google Scholar
  92. 92.
    Ye J, Tang S, Meng L, et al. Ultrasonic Control of Neural Activity through Activation of the Mechanosensitive Channel MscL. Nano Lett. 2018;18:4148–4155.Google Scholar
  93. 93.
    Plaksin M, Shoham S, Kimmel E. Intramembrane Cavitation as a Predictive Bio-Piezoelectric Mechanism for Ultrasonic Brain Stimulation. Phys. Rev. X. 2014;4:011004.Google Scholar
  94. 94.
    Sato T, Shapiro MG, Tsao DY. Ultrasonic Neuromodulation Causes Widespread Cortical Activation via an Indirect Auditory Mechanism. Neuron. 2018;98:1031–1041.e5.Google Scholar
  95. 95.
    Guo H, Hamilton M 2nd, Offutt SJ, et al. Ultrasound Produces Extensive Brain Activation via a Cochlear Pathway. Neuron. 2018;98:1020–1030.e4.Google Scholar
  96. 96.
    Mehić E, Xu JM, Caler CJ, et al. Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound. PLoS One. 2014;9:e86939.Google Scholar
  97. 97.
    Tufail Y, Yoshihiro A, Pati S, et al. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat. Protoc. 2011;6:1453–1470.Google Scholar
  98. 98.
    Khraiche ML, Phillips WB, Jackson N, et al. Ultrasound induced increase in excitability of single neurons. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2008;2008:4246–4249.Google Scholar
  99. 99.
    Legon W, Bansal P, Tyshynsky R, et al. Transcranial focused ultrasound neuromodulation of the human primary motor cortex. Sci. Rep. 2018;8:10007.Google Scholar
  100. 100.
    Legon W, Ai L, Bansal P, et al. Neuromodulation with single-element transcranial focused ultrasound in human thalamus. Hum. Brain Mapp. 2018;39:1995–2006.Google Scholar
  101. 101.
    Filonenko EA, Khokhlova VA. Effect of acoustic nonlinearity on heating of biological tissue by high-intensity focused ultrasound. Acoust. Phys. 2001;47:468–475.Google Scholar
  102. 102.
    Miranda PC. Physics of effects of transcranial brain stimulation. Handb. Clin. Neurol. 2013;116:353–366.Google Scholar
  103. 103.
    Hariz MI, Hariz G-M. Therapeutic stimulation versus ablation. Handb. Clin. Neurol. 2013;116:63–71.Google Scholar
  104. 104.
    Van Ness P, Skarpaas TC, Morrell M. Long-Term Outcome of Adults with Medically Intractable Mesial Temporal Lobe Seizures Treated with Responsive Neurostimulation (S52.001). Neurology. 2016;86:S52.001.Google Scholar
  105. 105.
    Khanna N, Gandhi D, Steven A, et al. Intracranial Applications of MR Imaging–Guided Focused Ultrasound. AJNR Am. J. Neuroradiol. [Internet]. 2016 [cited 2018 Jul 15]; Available from:
  106. 106.
    Fishman PS. Thalamotomy for essential tremor: FDA approval brings brain treatment with FUS to the clinic. J Ther Ultrasound. 2017;5:19.Google Scholar
  107. 107.
    Shukla ND, Ho AL, Pendharkar AV, et al. Laser interstitial thermal therapy for the treatment of epilepsy: evidence to date. Neuropsychiatr. Dis. Treat. 2017;13:2469–2475.Google Scholar
  108. 108.
    Schramm J. Temporal lobe epilepsy surgery and the quest for optimal extent of resection: a review. Epilepsia. 2008;49:1296–1307.Google Scholar
  109. 109.
    Rath SA, Braun V, Soliman N, et al. Results of DREZ coagulations for pain related to plexus lesions, spinal cord injuries and postherpetic neuralgia. Acta Neurochir. . 1996;138:364–369.Google Scholar
  110. 110.
    Mullan S, Lichtor T. Percutaneous microcompression of the trigeminal ganglion for trigeminal neuralgia. J. Neurosurg. 1983;59:1007–1012.Google Scholar
  111. 111.
    Monteith SJ, Medel R, Kassell NF, et al. Transcranial magnetic resonance–guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study. J. Neurosurg. 2013;118:319–328.Google Scholar
  112. 112.
    Payne AH, Hawryluk GW, Anzai Y, et al. Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability. Neural Regeneration Res. 2017;12:2045–2049.Google Scholar
  113. 113.
    Horodyckid C, Canney M, Vignot A, et al. Safe long-term repeated disruption of the blood-brain barrier using an implantable ultrasound device: a multiparametric study in a primate model. J. Neurosurg. 2017;126:1351–1361.Google Scholar
  114. 114.
    Hwang GM, Lani SW, Rosenberg AP, et al. Forward-looking engineering concepts for ultrasonic modulation of neural circuit activity in humans. Micro- and Nanotechnology Sensors, Systems, and Applications X. International Society for Optics and Photonics; 2018. p. 106391J.Google Scholar
  115. 115.
    Hynynen K, Jones RM. Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy. Phys. Med. Biol. 2016;61:R206–R248.Google Scholar
  116. 116.
    Rosnitskiy PB, Vysokanov BA, Gavrilov LR, et al. Method for Designing Multielement Fully Populated Random Phased Arrays for Ultrasound Surgery Applications. IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 2018;65:630–637.Google Scholar
  117. 117.
    Hynynen K, Clement GT, McDannold N, et al. 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. 2004;52:100–107.Google Scholar
  118. 118.
    Viessmann OM, Eckersley RJ, Christensen-Jeffries K, et al. Acoustic super-resolution with ultrasound and microbubbles. Phys. Med. Biol. 2013;58:6447–6458.Google Scholar
  119. 119.
    Errico C, Pierre J, Pezet S, et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature. 2015;527:499–502.Google Scholar
  120. 120.
    Hamani C, Richter E, Schwalb JM, et al. Bilateral subthalamic nucleus stimulation for Parkinson’s disease: a systematic review of the clinical literature. Neurosurgery. 2005;56:1313–1321; discussion 1321–1324.Google Scholar
  121. 121.
    Rosin B, Slovik M, Mitelman R, et al. Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron. 2011;72:370–384.Google Scholar
  122. 122.
    Little S, Pogosyan A, Neal S, et al. Adaptive deep brain stimulation in advanced Parkinson disease. Ann. Neurol. 2013;74:449–457.Google Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryUniversity of MinnesotaMinneapolisUSA

Personalised recommendations