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Focused ultrasound treatment for central nervous system disease: neurosurgeon’s perspectives

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Abstract

The concept of focused ultrasound (FUS) and its application in the field of medicine have been suggested since the mid-20th century. However, the clinical applications of this technique in central nervous system (CNS) diseases have been extremely limited because the skull inhibits efficient energy transmission. Therefore, early application of FUS treatment was only performed in patients who had already undergone invasive procedures including craniectomy and burr hole trephination. In the 1990s, the phased array technique was developed and this enabled the focus of ultrasonic energy through the skull, and in conjunction with another technique, magnetic resonance thermal monitoring, the possibility of applying FUS in the CNS was further strengthened. The first clinical trial using FUS treatment for CNS diseases was performed in the early 21st century in patients with glioblastoma, which consists of highly malignant primary brain tumors. However, this trial resulted in a failure to make lesions in the tumors. Various causes were suggested for this outcome including different acoustic impedances across heterogeneous intracranial tissue (not only brain tissue, but also fibrous or tumor tissue). To avoid the influence of this factor, the targets for FUS treatment were shifted to functional diseases such as essential tremor, Parkinson’s disease, and psychiatric disease, which usually occur in normal brain structures. The first trial for functional diseases was started in 2010, and the results were successful as accurate lesions were made in the target area. Nowadays, the indication of FUS treatment for functional CNS diseases is gradually widening, and many trials using the FUS technique are reporting good results. In addition to the lesioning technique using high intensity FUS treatment, the possibility of clinical application of low intensity FUS to CNS disease treatment has been investigated at a pre-clinical level, and it is expected that FUS treatment will become one of the most important novel techniques for the treatment of CNS diseases in the near future.

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References

  1. Heimburger RF. Report of the first international congress of neurological sciences, Brussels, Belgium, July 21–27, 1957. J Neurosurg. 1958;15(3):342–51.

    Article  Google Scholar 

  2. Lasak JM, Gorecki JP. The history of stereotactic radiosurgery and radiotherapy. Otolaryngol Clin N Am. 2009;42(4):593–9.

    Article  Google Scholar 

  3. Lynn JG, Putnam TJ. Histology of cerebral lesions produced by focused ultrasound. Am J Pathol. 1944;20(3):637–49.

    Google Scholar 

  4. Guthkelch A, Carter L, Cassady J, Hynynen K, Iacono R, Johnson P, Obbens E, Roemer R, Seeger J, Shimm D. Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial. J Neurooncol. 1991;10(3):271–84.

    Article  Google Scholar 

  5. Heimburger R. Ultrasound augmentation of central nervous system tumor therapy. Indiana Med. 1985;78(6):469–76.

    Google Scholar 

  6. Kenneth BO, Benkeser J, Leon A. An ultrasonic phased array applicator for hyperthermia. IEEE. 1984;31(5):527–31.

    Google Scholar 

  7. Heimburger R. Ultrasound augmentation of central nervous system tumor therapy. Indiana Med. 1985;78(6):469–76.

    Google Scholar 

  8. Samulski T, MacFall J, Zhang Y, Grant W, Charles C. Non-invasive thermometry using magnetic resonance diffusion imaging: potential for application in hyperthermic oncology. Int J Hyperther. 1992;8(6):819–29.

    Article  Google Scholar 

  9. Clement G, Hynynen K. A non-invasive method for focusing ultrasound through the human skull. Phys Med Biol. 2002;47(8):1219–36.

    Article  Google Scholar 

  10. McDannold N, Clement G, Black P, Jolesz F, Hynynen K. Transcranial MRI-guided focused ultrasound surgery of brain tumors: initial findings in three patients. Neurosurgery. 2010;66(2):323–32.

    Article  Google Scholar 

  11. Jeanmonod D, Werner B, Morel A, Michels L, Zadicario E, Schiff G, Martin E. Transcranial magnetic resonance imaging–guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus. 2012;32(1):E1.

    Article  Google Scholar 

  12. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999;83(3):389–400.

    Article  Google Scholar 

  13. Findley LJ, Koller WC. Essential tremor: a review. Neurology. 1987;37(7):1194.

    Article  Google Scholar 

  14. Chang WS, Chung JC, Kim JP, Chang JW. Simultaneous thalamic and posterior subthalamic electrode insertion with single deep brain stimulation electrode for essential tremor. Neuromodulation. 2013;16(3):236–43.

    Article  Google Scholar 

  15. Louis ED. Essential tremor. N Engl J Med. 2001;345(12):887–91.

    Article  Google Scholar 

  16. Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013;369(7):640–8.

    Article  Google Scholar 

  17. Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW. Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry. 2015;86(3):257–64.

    Article  Google Scholar 

  18. Chang JW, Min B-K, Kim B-S, Chang WS, Lee Y-H. Neurophysiologic correlates of sonication treatment in patients with essential tremor. Ultrasound Med Biol. 2015;41(1):124–31.

    Article  Google Scholar 

  19. Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, Schwartz M, Hynynen K, Lozano AM, Shah BB. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016;375(8):730–9.

    Article  Google Scholar 

  20. Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, Hynynen K, Lozano AM. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 2013;12(5):462–8.

    Article  Google Scholar 

  21. Rasmussen SA, Eisen JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatric Clin N Am. 1992;15(4):743–58.

    Google Scholar 

  22. Mian MK, Campos M, Sheth SA, Eskandar EN. Deep brain stimulation for obsessive-compulsive disorder: past, present, and future. Neurosurg Focus. 2010;29(2):E10.

    Article  Google Scholar 

  23. Chang WS, Roh D, Kim C-H, Chang JW. Combined bilateral anterior cingulotomy and ventral capsule/ventral striatum deep brain stimulation for refractory obsessive-compulsive disorder with major depression: do combined procedures have a long-term benefit? Restor Neurol Neurosci. 2013;31(6):723–32.

    Google Scholar 

  24. Jung H, Kim S, Roh D, Chang J, Chang W, Kweon E, Kim C, Chang J. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry. 2015;20:1205–11.

    Article  Google Scholar 

  25. Hynynen K, McDannold N, Sheikov NA, Jolesz FA, Vykhodtseva N. Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage. 2005;24(1):12–20.

    Article  Google Scholar 

  26. Liu H-L, Hua M-Y, Chen P-Y, Chu P-C, Pan C-H, Yang H-W, Huang C-Y, Wang J-J, Yen T-C, Wei K-C. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment 1. Radiology. 2010;255(2):415–25.

    Article  Google Scholar 

  27. Treat LH, McDannold N, Zhang Y, Vykhodtseva N, Hynynen K. Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Ultrasound Med Biol. 2012;38(10):1716–25.

    Article  Google Scholar 

  28. Alkins R, Burgess A, Kerbel R, Wels WS, Hynynen K. Early treatment of HER2-amplified brain tumors with targeted NK-92 cells and focused ultrasound improves survival. Neurooncology. 2016;18(7):974–81.

    Google Scholar 

  29. Min B-K, Bystritsky A, Jung K-I, Fischer K, Zhang Y, Maeng L-S, Park SI, Chung Y-A, Jolesz FA, Yoo S-S. Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. BMC Neurosci. 2011;12(1):23.

    Article  Google Scholar 

  30. Kim H, Taghados SJ, Fischer K, Maeng L-S, Park S, Yoo S-S. Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound. Ultrasound Med Biol. 2012;38(9):1568–75.

    Article  Google Scholar 

  31. Bystritsky A, Korb AS, Douglas PK, Cohen MS, Melega WP, Mulgaonkar AP, DeSalles A, Min B-K, Yoo S-S. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011;4(3):125–36.

    Article  Google Scholar 

  32. Burgess A, Ayala-Grosso CA, Ganguly M, Jordão JF, Aubert I, Hynynen K. Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier. Plos One. 2011;6(11):e27877.

    Article  Google Scholar 

  33. Ghanem A, Steingen C, Brenig F, Funcke F, Bai Z-Y, Hall C, Chin CT, Nickenig G, Bloch W, Tiemann K. Focused ultrasound-induced stimulation of microbubbles augments site-targeted engraftment of mesenchymal stem cells after acute myocardial infarction. J Mol Cell Cardiol. 2009;47(3):411–8.

    Article  Google Scholar 

  34. Burks SR, Ziadloo A, Kim SJ, Nguyen BA, Frank JA. Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications. Stem Cells. 2013;31(11):2551–60.

    Article  Google Scholar 

  35. Chan KY, Wang W, Wu JJ, Liu L, Theodoratou E, Car J, Middleton L, Russ TC, Deary IJ, Campbell H. Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990–2010: a systematic review and analysis. Lancet. 2013;381(9882):2016–23.

    Article  Google Scholar 

  36. Jordão JF, Ayala-Grosso CA, Markham K, Huang Y, Chopra R, McLaurin J, Hynynen K, Aubert I. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the TgCRND8 mouse model of Alzheimer’s disease. Plos One. 2010;5(5):e10549.

    Article  Google Scholar 

  37. Chang WS, Jung HH, Zadicario E, Rachmilevitch I, Tlusty T, Vitek S, Chang JW. Factors associated with successful magnetic resonance-guided focused ultrasound treatment: efficiency of acoustic energy delivery through the skull. J Neurosurg. 2016;124(2):411–6.

    Article  Google Scholar 

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Acknowledgement

This study was supported by the grant from the Yonsei University Future-leading Research Initiative (Yonsei Challenge) of 2015 (2015-22-0137) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1C1A1A02036851) and (2016M3C7A1914123)

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  1. Department of Neurosurgery, Brain Research Institute, Yonsei University College of Medicine, 205 Seongsanno, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Won Seok Chang & Jin Woo Chang

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  1. Won Seok Chang
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Correspondence to Jin Woo Chang.

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Chang, W.S., Chang, J.W. Focused ultrasound treatment for central nervous system disease: neurosurgeon’s perspectives. Biomed. Eng. Lett. 7, 107–114 (2017). https://doi.org/10.1007/s13534-017-0013-8

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  • DOI: https://doi.org/10.1007/s13534-017-0013-8

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