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A review of low-intensity focused ultrasound pulsation

  • Alexander Bystritsky
    Correspondence
    Correspondence: Alexander Bystritsky, MD, PhD, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, 300 UCLA Medical Plaza, 2335, Los Angeles, CA 90095.
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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  • Alex S. Korb
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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  • Pamela K. Douglas
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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  • Mark S. Cohen
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

    Center for Advanced Surgical and Interventional Technology (CASIT) and the Department of Biomedical Engineering, University of California, Los Angeles, Los Angeles, California

    Departments of Psychology, Neurology, Radiology, Biomedical Physics, University of California, Los Angeles, Los Angeles, California
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  • William P. Melega
    Affiliations
    Department of Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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  • Amit P. Mulgaonkar
    Affiliations
    Center for Advanced Surgical and Interventional Technology (CASIT) and the Department of Biomedical Engineering, University of California, Los Angeles, Los Angeles, California
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  • Antonio DeSalles
    Affiliations
    Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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  • Byoung-Kyong Min
    Affiliations
    Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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  • Seung-Schik Yoo
    Affiliations
    Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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Published:April 04, 2011DOI:https://doi.org/10.1016/j.brs.2011.03.007
      With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS) for Parkinson’s Disease, dystonia and obsessive compulsive disorder (OCD), vagus nerve stimulation (VNS) for epilepsy and depression, and repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression, neuromodulation has become increasingly relevant to clinical research. However, these techniques have significant drawbacks (eg, lack of special specificity and depth for the rTMS, and invasiveness and cumbersome maintenance for DBS). This article reviews the background, rationale, and pilot studies to date, using a new brain stimulation method—low-intensity focused ultrasound pulsation (LIFUP). The ability of ultrasound to be focused noninvasively through the skull anywhere within the brain, together with concurrent imaging (ie, functional magnetic resonance imaging [fMRI]) techniques, may create a role for research and clinical use of LIFUP. This technique is still in preclinical testing and needs to be assessed thoroughly before being advanced to clinical trials. In this study, we review over 50 years of research data on the use of focused ultrasound (FUS) in neuronal tissue and live brain, and propose novel applications of this noninvasive neuromodulation method.

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      References

        • Fry W.J.
        • Barnard J.W.
        • Fry F.J.
        • Brennan J.F.
        Ultrasonically produced localized selective lesions in the central nervous system.
        Am J Phys Med. 1955; 34: 413-423
        • Gavrilov L.R.
        • Gersuni G.V.
        • Ilyinsky O.B.
        • et al.
        The effect of focused ultrasound on the skin and deep nerve structures of man and animal.
        Prog Brain Res. 1976; 43: 279-292
        • Fry W.J.
        Intense ultrasound in investigations of the central nervous system.
        Adv Biol Med Phys. 1958; 6: 281-348
        • Fry W.J.
        Use of intense ultrasound in neurological research.
        Am J Phys Med. 1958; 37: 143-147
        • Martin E.
        • Jeanmonod D.
        • Morel A.
        • Zadicario E.
        • Werner B.
        High-intensity focused ultrasound for noninvasive functional neurosurgery.
        Ann Neurol. 2009; 66: 858-861
        • Fry F.J.
        • Ades H.W.
        • Fry W.J.
        Production of reversible changes in the central nervous system by ultrasound.
        Science. 1958; 127: 83-84
        • Morris 3rd, G.L.
        • Mueller W.M.
        Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05.
        Neurology. 1999; 53: 1731-1735
        • Groves D.A.
        • Brown V.J.
        Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects.
        Neurosci Biobehav Rev. 2005; 29: 493-500
        • Ansari S.
        • Chaudhri K.
        • Al Moutaery K.A.
        Vagus nerve stimulation: indications and limitations.
        Acta Neurochir Suppl. 2007; 97: 281-286
        • Dowling J.
        Deep brain stimulation: current and emerging indications.
        Mo Med. 2008; 105: 424-428
        • Grover P.J.
        • Pereira E.A.
        • Green A.L.
        • et al.
        Deep brain stimulation for cluster headache.
        J Clin Neurosci. 2009; 16: 861-866
        • Collins K.L.
        • Lehmann E.M.
        • Patil P.G.
        Deep brain stimulation for movement disorders.
        Neurobiol Dis. 2010; 38: 338-345
        • Ellis T.L.
        • Stevens A.
        Deep brain stimulation for medically refractory epilepsy.
        Neurosurg Focus. 2008; 25: E11
        • Gutman D.A.
        • Holtzheimer P.E.
        • Behrens T.E.
        • Johansen-Berg H.
        • Mayberg H.S.
        A tractography analysis of two deep brain stimulation white matter targets for depression.
        Biol Psychiatry. 2009; 65: 276-282
        • Mian M.K.
        • Campos M.
        • Sheth S.A.
        • Eskandar E.N.
        Deep brain stimulation for obsessive-compulsive disorder: past, present, and future.
        Neurosurg Focus. 2010; 29: E10
        • Lefaucheur J.P.
        Methods of therapeutic cortical stimulation.
        Neurophysiol Clin. 2009; 39: 1-14
        • Burt T.
        • Lisanby S.H.
        • Sackeim H.A.
        Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis.
        Int J Neuropsychopharmacol. 2002; 5: 73-103
        • Rothwell J.
        Transcranial magnetic stimulation as a method for investigating the plasticity of the brain in Parkinson’s disease and dystonia.
        Parkinsonism Relat Disord. 2007; 13: S417-S420
        • George M.S.
        Transcranial magnetic stimulation for the treatment of depression.
        Expert Rev Neurother. 2010; 10: 1761-1772
        • Kimiskidis V.K.
        Transcranial magnetic stimulation for drug-resistant epilepsies: rationale and clinical experience.
        Eur Neurol. 2010; 63: 205-210
        • Lipton R.B.
        • Pearlman S.H.
        Transcranial magnetic simulation in the treatment of migraine.
        Neurotherapeutics. 2010; 7: 204-212
        • Bystritsky A.
        • Kerwin L.
        • Feusner J.
        A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder.
        J Clin Psychiatry. 2008; 69: 412-417
        • Nitsche M.A.
        • Boggio P.S.
        • Fregni F.
        • Pascual-Leone A.
        Treatment of depression with transcranial direct current stimulation (tDCS): a review.
        Exp Neurol. 2009; 219: 14-19
        • DeGiorgio C.M.
        • Murray D.
        • Markovic D.
        • Whitehurst T.
        Trigeminal nerve stimulation for epilepsy: long-term feasibility and efficacy.
        Neurology. 2009; 72: 936-938
        • Bronstein J.M.
        • Tagliati M.
        • Alterman R.L.
        • et al.
        Deep brain stimulation for Parkinson Disease: an expert consensus and review of key issues.
        Arch Neurol. 2011; 68: 165
        • Rauch S.L.
        • Dougherty D.D.
        • Malone D.
        • et al.
        A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder.
        J Neurosurg. 2006; 104: 558-565
        • Dormont D.
        • Seidenwurm D.
        • Galanaud D.
        • Cornu P.
        • Yelnik J.
        • Bardinet E.
        Neuroimaging and deep brain stimulation.
        AJNR Am J Neuroradiol. 2010; 31: 5-23
        • Rezai A.R.
        • Phillips M.
        • Baker K.B.
        • et al.
        Neurostimulation system used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations.
        Invest Radiol. 2004; 39: 300
        • Baker K.B.
        • Tkach J.
        • et al.
        Reduction of magnetic resonance imaging-related heating in deep brain stimulation leads using a lead management device.
        Neurosurgery. 2005; 57: 392
        • Henderson J.M.
        • Tkach J.
        • Phillips M.
        • Baker K.
        • Shellock F.G.
        • Rezai A.R.
        Permanent neurological deficit related to magnetic resonance imaging in a patient with implanted deep brain stimulation electrodes for Parkinson’s disease: case report.
        Neurosurgery. 2005; 57: E1063
        • Levkovitz Y.
        • Roth Y.
        • Harel E.V.
        • Braw Y.
        • Sheer A.
        • Zangen A.
        A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation.
        Clin Neurophysiol. 2007; 118: 2730-2744
        • Baudewig J.
        • Paulus W.
        • Frahm J.
        Artifacts caused by transcranial magnetic stimulation coils and EEG electrodes in T2∗-weighted echo-planar imaging.
        Magn Reson Imaging. 2000; 18: 479-484
        • Baudewig J.
        • Siebner H.R.
        • Bestmann S.
        • et al.
        Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS).
        Neuroreport. 2001; 12: 3543
        • Nahas Z.
        • Li X.
        • Kozel F.A.
        • et al.
        Safety and benefits of distance-adjusted prefrontal transcranial magnetic stimulation in depressed patients 55-75 years of age: a pilot study.
        Depress Anxiety. 2004; 19: 249-256
        • Bohning D.E.
        • Denslow S.
        • Bohning P.A.
        • Lomarev M.P.
        • George M.S.
        Interleaving fMRI and rTMS.
        Suppl Clin Neurophysiol. 2003; 56: 42-54
        • Wu A.D.
        Functional neuroimaging and repetitive transcranial magnetic stimulation in Parkinson’s disease.
        Rev Neurol Dis. 2007; 4: 1-9
        • Bystritsky A.
        • Kerwin L.E.
        • Feusner J.D.
        A preliminary study of fMRI-guided rTMS in the treatment of generalized anxiety disorder: 6-month follow-up.
        J Clin Psychiatry. 2009; 70: 431-432
        • Langguth B.
        • Kleinjung T.
        • Landgrebe M.
        • de Ridder D.
        • Hajak G.
        rTMS for the treatment of tinnitus: the role of neuronavigation for coil positioning.
        Neurophysiol Clin. 2010; 40: 45-58
      1. Bystritsky A. Methods for modifying electrical currents in neuronal circuits, USPTO Patent, Full-Text and Image Database (AppFT, USPTO). 7,283,861, April, 2002.

        • Singh V.
        • McCartney J.P.
        • Hemphill 3rd, J.C.
        Transcranial Doppler ultrasonography in the neurologic intensive care unit.
        Neurol India. 2001; 49: S81-S89
        • Suzuki R.
        • Asai J.
        • et al.
        Transcranial echo-guided transsphenoidal surgical approach for the removal of large macroadenomas.
        J Neurosurg. 2004; 100: 68-72
        • Alexandrov A.V.
        • Demchuk A.M.
        • Burgin W.S.
        • Robinson D.J.
        • Grotta J.C.
        Ultrasound-enhanced thrombolysis for acute ischemic stroke: phase I, findings of the CLOTBUST trial.
        J Neuroimaging. 2004; 14: 113-117
        • Tsivgoulis G.
        • Eggers J.
        • Ribo M.
        • et al.
        Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies.
        Stroke. 2010; 41: 280-287
        • Yagita Y.
        • Etani H.
        • Handa N.
        • et al.
        Effect of transcranial Doppler intensity on successful recording in Japanese patients.
        Ultrasound Med Biol. 1996; 22: 701-705
        • Houston L.E.
        • Odibo A.O.
        • Macones G.A.
        The safety of obstetrical ultrasound: a review.
        Prenat Diagn. 2009; 29: 1204-1212
        • Jolesz F.A.
        • Hynynen K.
        Magnetic resonance image-guided focused ultrasound surgery.
        Cancer J. 2002; 8: S100-S112
        • Hynynen K.
        • Jolesz F.A.
        Demonstration of potential noninvasive ultrasound brain therapy through an intact skull.
        Ultrasound Med Biol. 1998; 24: 275-283
        • McDannold N.
        • Hynynen K.
        • Wolf D.
        • Wolf G.
        • Jolesz F.
        MRI evaluation of thermal ablation of tumors with focused ultrasound.
        J Magn Reson Imaging. 1998; 8: 91-100
        • Sun J.
        • Hynynen K.
        Focusing of therapeutic ultrasound through a human skull: a numerical study.
        J Acoust Soc Am. 1998; 104: 1705-1715
        • Jolesz F.A.
        MRI-guided focused ultrasound surgery.
        Annu Rev Med. 2009; 60: 417-430
        • Harvey EN
        The effect of high frequency sound waves on heart muscle and other irritable tissues.
        Am J Physiol. 1929; 91: 284-290
        • Benedetti E.
        [Neuroacoustic potentials produced by ultrasounds in some orthoptera.].
        Boll Soc Ital Biol Sper. 1950; 26: 741-743
        • Schikorski K.
        [Effect of ultrasonics on the central nervous system; seen from the viewpoint of a sound theory of function of the central nervous system.].
        Strahlentherapie. 1952; 87: 556-566
        • Chauchard B.
        • Chauchard P.
        • Mazoue H.
        [Research on nerve irritation.].
        C R Seances Soc Biol Fil. 1953; 147: 1869-1871
        • Chauchard P.
        • Mazoue H.
        • Busnel RG.
        • Gligorijevic J.
        [Physiologic fundamentals of the therapeutic action of ultrasonics.].
        Presse Med. 1953; 61: 628-629
        • Mazoue H.
        • Chauchard P.
        • et al.
        [Nervous excitation with high frequency ultrasonics.].
        J Physiol (Paris). 1953; 45: 179-182
        • Allegranza A.
        [Ultrasonics and the central nervous system.].
        Minerva Fisioter Radiobiol. 1956; 1: 26-32
        • Fry F.J.
        Precision high intensity focusing ultrasonic machines for surgery.
        Am J Phys Med. 1958; 37: 152-156
        • Gavrilov L.R.
        • Tsirul’nikov E.M.
        • Shchekanov EE
        [Responses of the auditory centers of the frog midbrain to labyrinth stimulation by focused ultrasound].
        Fiziol Zh SSSR Im I M Sechenova. 1975; 61: 213-221
        • Adrianov O.S.
        • Vykhodtseva N.I.
        • Fokin V.F.
        • Uranova N.A.
        • Avirom V.M.
        [Reversible functional shutdown of the optic tract on exposure to focused ultrasound].
        Biull Eksp Biol Med. 1984; 97: 760-762
        • Adrianov O.S.
        • Vykhodtseva N.I.
        • Gavrilov L.R.
        [Use of focused ultrasound for local effects on deep brain structures].
        Fiziol Zh SSSR Im I M Sechenova. 1984; 70: 1157-1166
        • Gavrilov L.R.
        Use of focused ultrasound for stimulation of nerve structures.
        Ultrasonics. 1984; 22: 132-138
        • Lele P.P.
        Effects of focused ultrasonic radiation on peripheral nerve, with observations on local heating.
        Exp Neurol. 1963; 8: 47-83
        • Foster K.R.
        • Wiederhold M.L.
        Auditory responses in cats produced by pulsed ultrasound.
        J Acoust Soc Am. 1978; 63: 1199-1205
        • Velling V.A.
        • Shklyaruk S.P.
        Modulation of the functional state of the brain with the aid of focused ultrasonic action.
        Neurosci Behav Physiol. 1988; 18: 369-375
        • Rinaldi P.C.
        • Jones J.P.
        • Reines F.
        • Price L.R.
        Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation.
        Brain Res. 1991; 558: 36-42
        • Jolesz F.A.
        • Hynynen K.
        • et al.
        Noninvasive thermal ablation of hepatocellular carcinoma by using magnetic resonance imaging-guided focused ultrasound.
        Gastroenterology. 2004; 127: S242-S247
        • Trubestein G.
        • Engel C.
        • Etzel F.
        • Sobbe A.
        • Cremer H.
        • Stumpff U.
        Thrombolysis by ultrasound.
        Clin Sci Mol Med Suppl. 1976; 3: 697s-698s
        • Balucani C.
        • Alexandrov A.V.
        Ultrasound- and microspheres-enhanced thrombolysis for stroke treatment: state of the art.
        Curr Cardiol Rep. 2010; 12: 34-41
        • Foley J.L.
        • Little J.W.
        • Starr 3rd, F.L.
        • Frantz C.
        • Vaezy S.
        Image-guided HIFU neurolysis of peripheral nerves to treat spasticity and pain.
        Ultrasound Med Biol. 2004; 30: 1199-1207
        • Foley J.L.
        • Little J.W.
        • Vaezy S.
        Image-guided high-intensity focused ultrasound for conduction block of peripheral nerves.
        Ann Biomed Eng. 2007; 35: 109-119
        • Foley J.L.
        • Little J.W.
        • Vaezy S.
        Effects of high-intensity focused ultrasound on nerve conduction.
        Muscle Nerve. 2008; 37: 241-250
        • Sheikov N.
        • McDannold N.
        • Vykhodtseva N.
        • Jolesz F.
        • Hynynen K.
        Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles.
        Ultrasound Med Biol. 2004; 30: 979-989
        • McDannold N.
        • Vykhodtseva N.
        • Hynynen K.
        Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption.
        Ultrasound Med Biol. 2008; 34: 930-937
        • McDannold N.
        • Vykhodtseva N.
        • Raymond S.
        • Jolesz F.A.
        • Hynynen K.
        MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.
        Ultrasound Med Biol. 2005; 31: 1527-1537
        • Busse J.W.
        • Morton E.
        • Lacchetti C.
        • Guyatt G.H.
        • Bhandari M.
        Current management of tibial shaft fractures: a survey of 450 Canadian orthopedic trauma surgeons.
        Acta Orthop. 2008; 79: 689-694
        • 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
        • Tyler W.J.
        • Tufail Y.
        • Finsterwald M.
        • Tauchmann M.L.
        • Olson E.J.
        • Majestic C.
        Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound.
        PLoS One. 2008; 3: e3511
        • Tufail Y.
        • Matyushov A.
        • Baldwin N.
        • et al.
        Transcranial pulsed ultrasound stimulates intact brain circuits.
        Neuron. 2010; 66: 681-694
        • Colucci V.
        • Strichartz G.
        • Jolesz F.
        • Vykhodtseva N.
        • Hynynen K.
        Focused ultrasound effects on nerve action potential in vitro.
        Ultrasound Med Biol. 2009; 35: 1737-1747
      2. Yoo SS, Lee JH, Zhang Y, et al. FUS-mediated reversible modulation of region-specific brain function. Washington DC: Proceedings of MRgFUS; 2008. pp. 10.

      3. Yoo SS, Lee JH, Fischer K, et al. Non-invasive regional modulation of brain function by focused ultrasound. Proceedings of Society for Neuroscience; 2009. pp. 105.111.

      4. Yoo SS, Bystritsky A, Lee JH, et al. Focused ultrasound modulates region-specific brain activity. Neuroimage 2011 February 24 (Epub ahead of print).

      5. Yoo SS, Min BK, Zhang Y, McDannold N, Bystritsky A, Jolesz FA. (2010). Non-invasive suppression of animal-model chronic epilepsy using image-guided focused ultrasound. Proceeding of SMRM-ESMRMB Joint Annual Meeting in Stockholm, Sweden, (May 4): Abrsract 2197.

        • Tyler W.J.
        • Tufail Y.
        • Pati S.
        Pain: noninvasive functional neurosurgery using ultrasound.
        Nat Rev Neurol. 2010; 6: 13-14
        • Fry W.J.
        • Fry R.B.
        A possible mechanism involved in the conduction process of thin sheathed nerve fibers.
        J Cell Physiol. 1950; 36: 229-239
        • ter Haar G.
        Therapeutic applications of ultrasound.
        Prog Biophys Mol Biol. 2007; 93: 111-129
        • Ishibashi K.
        • Shimada K.
        • Kawato T.
        • et al.
        Inhibitory effects of low-energy pulsed ultrasonic stimulation on cell surface protein antigen C through heat shock proteins GroEL and DnaK in Streptococcus mutans.
        Appl Environ Microbiol. 2010; 76: 751-756
        • Coakley W.T.
        • Dunn F.
        Degradation of DNA in high-intensity focused ultrasonic fields at 1 MHz.
        J Acoust Soc Am. 1971; 50: 1539-1545
        • Heckman J.D.
        • Ryaby J.P.
        • McCabe J.
        • Frey J.J.
        • Kilcoyne R.F.
        Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound.
        J Bone Joint Surg Am. 1994; 76: 26-34
        • Gavrilov L.R.
        • Tsirulnikov E.M.
        • Davies I.A.
        Application of focused ultrasound for the stimulation of neural structures.
        Ultrasound Med Biol. 1996; 22: 179-192
        • Bachtold M.R.
        • Rinaldi P.C.
        • Jones J.P.
        • Reines F.
        • Price L.R.
        Focused ultrasound modifications of neural circuit activity in a mammalian brain.
        Ultrasound Med Biol. 1998; 24: 557-565
        • Bailey M.R.
        • Dalecki D.
        • et al.
        Bioeffects of positive and negative acoustic pressures in vivo.
        J Acoust Soc Am. 1996; 100: 3941-3946
        • Wall P.D.
        • Fry W.J.
        • Stephens R.
        • Tucker D.
        • Lettvin J.Y.
        Changes produced in the central nervous system by ultrasound.
        Science. 1951; 114: 686-687
        • Mihran R.T.
        • Barnes F.S.
        • Wachtel H.
        Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse.
        Ultrasound Med Biol. 1990; 16: 297-309
        • Fry W.J.
        • Mosberg Jr., W.H.
        • Barnard J.W.
        • Fry F.J.
        Production of focal destructive lesions in the central nervous system with ultrasound.
        J Neurosurg. 1954; 11: 471-478
        • Sachs F.
        Stretch-activated ion channels: what are they?.
        Physiology (Bethesda). 2010; 25: 50-56
        • Boland L.M.
        • Drzewiecki M.M.
        Polyunsaturated fatty acid modulation of voltage-gated ion channels.
        Cell Biochem Biophys. 2008; 52: 59-84
        • Morris C.E.
        • Juranka P.F.
        Nav channel mechanosensitivity: activation and inactivation accelerate reversibly with stretch.
        Biophys J. 2007; 93: 822-833
        • Ochs S
        • Pourmand R
        • Si K
        • Friedman RN
        Stretch of mammalian nerve in vitro: effect on compound action potentials.
        J Peripher Nerv Syst. 2000; 5: 227-235
        • Altland O.D.
        • Dalecki D.
        • Suchkova V.N.
        • Francis C.W.
        Low-intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis.
        J Thromb Haemost. 2004; 2: 637-643
        • Iida K.
        • Luo H.
        • Hagisawa T.
        • et al.
        Noninvasive low-frequency ultrasound energy causes vasodilation in humans.
        J Am Coll Cardiol. 2006; 48: 532-537
        • Sugita Y.
        • Mizuno S.
        • Nakayama N.
        • et al.
        Nitric oxide generation directly responds to ultrasound exposure.
        Ultrasound Med Biol. 2008; 34: 487-493
        • Tyler W.J.
        Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis.
        Neuroscientist. 2010;
        • Sheikov N.
        • McDannold N.
        • Jolesz F.A.
        • Zhang Y.-Z.
        • Tam K.
        • Hynynen K.
        Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier.
        Ultrasound Med Biol. 2006; 32: 1399-1409
        • Min B.K.
        • Bystritsky A.
        • Jung K.L.
        • et al.
        Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.
        BMC Neurosci. 2011; 12: 23
        • Jolesz F.A.
        • Hynynen K.
        • McDannold N.
        • Tempany C.
        MR imaging-controlled focused ultrasound ablation: a noninvasive image-guided surgery.
        Magn Reson Imaging Clin N Am. 2005; 13: 545-560
        • Lacan G.
        • De Salles A.A.
        • et al.
        Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey: laboratory investigation.
        J Neurosurg. 2008; 108: 336-342
        • Vykhodtseva N.
        • Sorrentino V.
        • Jolesz F.A.
        • Bronson R.T.
        • Hynynen K.
        MRI detection of the thermal effects of focused ultrasound on the brain.
        Ultrasound Med Biol. 2000; 26: 871-880
        • Seror O.
        • Lepetit-Coiffe M.
        • Le Bail B.
        • et al.
        Real time monitoring of radiofrequency ablation based on MR thermometry and thermal dose in the pig liver in vivo.
        Eur Radiol. 2008; 18: 408-416
        • Hertzberg Y.
        • Volovick A.
        • Zur Y.
        • Medan Y.
        • Vitek S.
        • Navon G.
        Ultrasound focusing using magnetic resonance acoustic radiation force imaging: application to ultrasound transcranial therapy.
        Med Phys. 2010; 37: 2934-2942
        • Kaye E.A.
        • Chen J.
        • et al.
        Rapid MR-ARFI method for focal spot localization during focused ultrasound therapy.
        Magn Reson Med. 2010;