Chun-I Yeh1,2,3, Mei-Fang Cheng4, Furen Xiao5, Yi-Chieh Chen4, Chien-Chu Liu4, Hung-Yi Chen5, Ruoh-Fang Yen4, Yu-Ten Ju6, Yilin Chen7, Mohan Bodduluri8,9, Pin-Huan Yu7, Chau-Hwa Chi7, Ngot Swan Chong8,10, Liang-Hsiang Wu8,9, John R Adler8,9,11, Michael Bret Schneider9,11,12. 1. Department of Psychology, National Taiwan University, Taipei, Taiwan. 2. Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan. 3. Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan. 4. Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. 6. Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. 7. Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan. 8. Zap Medical System, Inc., Cayman Islands, UK. 9. Zap Surgical Systems, Inc., San Carlos, CA, USA. 10. Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan. 11. Department of Neurosurgery, Stanford University, Stanford, CA, USA. 12. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Abstract
OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.
OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.
Authors: Hamed Zaer; Wei Fan; Dariusz Orlowski; Andreas N Glud; Anne S M Andersen; M Bret Schneider; John R Adler; Albrecht Stroh; Jens C H Sørensen Journal: Front Hum Neurosci Date: 2020-11-23 Impact factor: 3.169