John M Stern1, Norman M Spivak2, Sergio A Becerra3, Taylor P Kuhn3, Alexander S Korb4, David Kronemyer3, Négar Khanlou5, Samuel D Reyes6, Martin M Monti7, Caroline Schnakers6, Patricia Walshaw3, Inna Keselman1, Mark S Cohen8, William Yong5, Itzhak Fried9, Sheldon E Jordan10, Mark E Schafer11, Jerome Engel12, Alexander Bystritsky13. 1. Department of Neurology, UCLA School of Medicine, USA. 2. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA; Department of Neurosurgery, UCLA School of Medicine, USA. 3. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA. 4. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA; BrainSonix Inc., Los Angeles, CA, USA. 5. Department of Pathology and Laboratory Medicine, UCLA School of Medicine, USA. 6. Department of Neurosurgery, UCLA School of Medicine, USA. 7. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA; Department of Neurosurgery, UCLA School of Medicine, USA; Department of Psychology, UCLA College of Letters and Science, USA; Brain Research Institute, UCLA, USA. 8. Department of Neurology, UCLA School of Medicine, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA; Department of Psychology, UCLA College of Letters and Science, USA; Department of Radiology, UCLA School of Medicine, USA; Department of Biomedical Physics, UCLA School of Medicine, USA; Department of Bioengineering, UCLA School of Engineering, USA; California Nanosystems Institute, UCLA, USA; Brain Research Institute, UCLA, USA. 9. Department of Neurosurgery, UCLA School of Medicine, USA; Brain Research Institute, UCLA, USA. 10. Neurology Management Associates- Los Angeles, Santa Monica, CA, USA. 11. BrainSonix Inc., Los Angeles, CA, USA; School of Biomedical Engineering, Drexel University, Philadelphia, PA, USA. 12. Department of Neurology, UCLA School of Medicine, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA; Department of Neurobiology, UCLA School of Medicine, USA; Brain Research Institute, UCLA, USA. 13. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, USA; BrainSonix Inc., Los Angeles, CA, USA. Electronic address: abystritsky@mednet.ucla.edu.
Abstract
OBJECTIVE: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. METHODS: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. RESULTS: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. SIGNIFICANCE: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.
OBJECTIVE: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. METHODS: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. RESULTS: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. SIGNIFICANCE: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.
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