In vivo transcranial brain surgery with an ultrasonic time reversal mirror.

OBJECT High-intensity focused ultrasonography is known to induce controlled and selective noninvasive destruction of tissues by focusing ultrasonic beams within organs, like a magnifying glass concentrating enough sunlight to burn a hole in paper. Such a technique should be highly interesting for the treatment of deep-seated lesions in the brain. Nevertheless, ultrasonic tissue ablation in the brain has long been hampered by the defocusing effect of the skull bone. METHODS In this in vivo study, the authors used a high-power time-reversal mirror specially designed for noninvasive ultrasonic brain treatment to induce thermal lesions through the skulls of 10 sheep. The sheep were divided into three groups and, depending on group, were killed 1, 2, or 3 weeks after treatment. The thermal lesions were confirmed based on findings of posttreatment magnetic resonance imaging and histological examinations. After treatment, the basic neurological functions of the animals were unchanged: the animals recovered from anesthesia without any abnormal delay and did not exhibit signs of paralysis or coma. No major behavioral change was observed. CONCLUSIONS The results provide striking evidence that noninvasive ultrasonographic brain surgery is feasible. Thus the authors offer a novel noninvasive method of performing local brain ablation in animals for behavioral studies. This technique may lead the way to noninvasive and nonionizing treatment of brain tumors and neurological disorders by selectively targeting intracranial lesions. Nevertheless, sheep do not represent a good functional model and extensive work will need to be conducted preferably on monkeys to investigate the effects of this treatment.

[1]  J. Kennedy High-intensity focused ultrasound in the treatment of solid tumours , 2005, Nature Reviews Cancer.

[2]  A. Gelet,et al.  Technology Insight: high-intensity focused ultrasound for urologic cancers , 2005, Nature Clinical Practice Urology.

[3]  J. Loeffler Can combined whole brain radiation therapy and radiosurgery improve the treatment of single brain metastases? , 2004, Nature Clinical Practice Oncology.

[4]  Kullervo Hynynen,et al.  Patterns of thermal deposition in the skull during transcranial focused ultrasound surgery , 2004, IEEE Transactions on Biomedical Engineering.

[5]  Natalia Vykhodtseva,et al.  500‐element ultrasound phased array system for noninvasive focal surgery of the brain: A preliminary rabbit study with ex vivo human skulls , 2004, Magnetic resonance in medicine.

[6]  F. Gleeson,et al.  High-intensity focused ultrasound for the treatment of liver tumours. , 2004, Ultrasonics.

[7]  Wen-Zhi Chen,et al.  Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. , 2003, The Journal of urology.

[8]  Guy Vallancien,et al.  High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. , 2003, Journal of endourology.

[9]  M Pernot,et al.  High power transcranial beam steering for ultrasonic brain therapy. , 2003, Physics in medicine and biology.

[10]  R. Killiany,et al.  MRI‐guided focused ultrasound surgery in the brain: Tests in a primate model , 2003, Magnetic resonance in medicine.

[11]  M Tanter,et al.  Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans. , 2003, The Journal of the Acoustical Society of America.

[12]  Gregory T. Clement,et al.  A non-invasive method for focusing ultrasound through the human skull. , 2002, Physics in medicine and biology.

[13]  L. Hau Taming light with cold atoms , 2001 .

[14]  G. Haar,et al.  High Intensity Focused Ultrasound for the Treatment of Tumors , 2001, Echocardiography.

[15]  Y. Miyashita,et al.  Top-down signal from prefrontal cortex in executive control of memory retrieval , 1999, Nature.

[16]  K. Hynynen,et al.  Focusing of therapeutic ultrasound through a human skull: a numerical study. , 1998, The Journal of the Acoustical Society of America.

[17]  Daniel R. Weinberger,et al.  Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine , 1998, Nature.

[18]  F A Jolesz,et al.  Demonstration of potential noninvasive ultrasound brain therapy through an intact skull. , 1998, Ultrasound in medicine & biology.

[19]  M. Fink Time reversed acoustics , 1997 .

[20]  J.-L. Thomas,et al.  Ultrasonic beam focusing through tissue inhomogeneities with a time reversal mirror: application to transskull therapy , 1996, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[21]  Ferenc A. Jolesz,et al.  MR‐Guided Focused Ultrasound Surgery , 1992, Journal of computer assisted tomography.

[22]  R. B. Roemer,et al.  Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial , 1991, Journal of Neuro-Oncology.

[23]  G. Haar,et al.  High intensity focused ultrasound--a surgical technique for the treatment of discrete liver tumours. , 1989, Physics in medicine and biology.

[24]  J. Campbell,et al.  The deformation of the ultrasonic field in passage across the living and cadaver head , 1969, Medical and biological engineering.

[25]  W J FRY,et al.  Ultrasonic lesions in the mammalian central nervous system. , 1955, Science.

[26]  W. Fry Ultrasound in Neurology , 1955, Neurology.

[27]  W J FRY,et al.  Production of focal destructive lesions in the central nervous system with ultrasound. , 1954, Journal of neurosurgery.

[28]  J. Ganz Gamma knife radiosurgery and its possible relationship to malignancy: a review. , 2002, Journal of neurosurgery.

[29]  L. Crum,et al.  Image-guided acoustic therapy. , 2001, Annual review of biomedical engineering.

[30]  J Y Chapelon,et al.  New piezoelectric transducers for therapeutic ultrasound. , 2000, Ultrasound in medicine & biology.

[31]  Wang Hong,et al.  HIGH INTENSITY FOCUSED ULTRASOUND FOR TUMOR TREATMENT , 2000 .

[32]  K. Hynynen,et al.  A 256-element ultrasonic phased array system for the treatment of large volumes of deep seated tissue , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[33]  J M Dubernard,et al.  Treatment of prostate cancer with transrectal focused ultrasound: early clinical experience. , 1996, European urology.

[34]  K Hynynen,et al.  Pulse duration and peak intensity during focused ultrasound surgery: theoretical and experimental effects in rabbit brain in vivo. , 1994, Ultrasound in medicine & biology.