|
|
低强度聚集超声在神经系统疾病治疗中的研究进展
|
Abstract:
无创神经调节技术是治疗神经系统疾病的重要手段，多个研究证明低强度聚集超声(Low-intensity focused ultrasound, LIFU)可应用于多种神经系统疾病，如癫痫、阿尔茨海默病、帕金森病等，并显现出了积极的疗效。LIFU可以穿透颅骨，聚集于大脑深部核团，具有无创、高精确性、高穿透深度等优点。本文通过回顾LIFU的技术进展、作用机制以及在神经系统疾病治疗中的应用，总结了LIFU作为一种新型的无创神经调节技术，在神经系统疾病治疗方面的应用前景。研究表明，LIFU通过靶向调控神经元活性及神经可塑性，可能具有改善神经功能障碍的临床转化价值。本综述为LIFU技术的科学化应用与临床转化研究提供了理论框架与方法学参考。
Noninvasive neuromodulation techniques are important for the treatment of neurological diseases. Several studies have demonstrated that low-intensity focused ultrasound (LIFU) can be utilized in various neurological diseases, such as epilepsy, Alzheimer’s disease, and Parkinson’s disease, with promising therapeutic effects. LIFU has the ability to penetrate the skull and target deep brain structures, offering advantages such as non-invasiveness, high precision, and significant depth of penetration. This review discusses the technical advancements, mechanisms of action, and clinical applications of LIFU in treating neurological diseases. It summarizes the potential of LIFU as a novel non-invasive neuromodulation technology for the treatment of neurological diseases. The study suggests that LIFU may have clinical translational value in improving neurological dysfunction by targeting and modulating neuronal activity and neuroplasticity. This review provides a theoretical framework and methodological reference for the scientific application and clinical translational research of LIFU technology.
| [1] | Yang, P., Phipps, M.A., Jonathan, S., Newton, A.T., Byun, N., Gore, J.C., et al. (2021) Bidirectional and State-Dependent Modulation of Brain Activity by Transcranial Focused Ultrasound in Non-Human Primates. Brain Stimulation, 14, 261-272. https://doi.org/10.1016/j.brs.2021.01.006 |
| [2] | Duque, M., Lee-Kubli, C.A., Tufail, Y., Magaram, U., Patel, J., Chakraborty, A., et al. (2022) Sonogenetic Control of Mammalian Cells Using Exogenous Transient Receptor Potential A1 Channels. Nature Communications, 13, Article No. 600. https://doi.org/10.1038/s41467-022-28205-y |
| [3] | Liang, D., Chen, J., Zhou, W., Chen, J., Chen, W. and Wang, Y. (2019) Alleviation Effects and Mechanisms of Low‐intensity Focused Ultrasound on Pain Triggered by Soft Tissue Injury. Journal of Ultrasound in Medicine, 39, 997-1005. https://doi.org/10.1002/jum.15185 |
| [4] | Pang, N., Huang, X., Zhou, H., Xia, X., Liu, X., Wang, Y., et al. (2021) Transcranial Ultrasound Stimulation of Hypothalamus in Aging Mice. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 68, 29-37. https://doi.org/10.1109/tuffc.2020.2968479 |
| [5] | Xu, T., Lu, X., Peng, D., Wang, G., Chen, C., Liu, W., et al. (2020) Ultrasonic Stimulation of the Brain to Enhance the Release of Dopamine—A Potential Novel Treatment for Parkinson’s Disease. Ultrasonics Sonochemistry, 63, Article ID: 104955. https://doi.org/10.1016/j.ultsonch.2019.104955 |
| [6] | Bobola, M.S., Chen, L., Ezeokeke, C.K., Olmstead, T.A., Nguyen, C., Sahota, A., et al. (2020) Transcranial Focused Ultrasound, Pulsed at 40 Hz, Activates Microglia Acutely and Reduces Aβ Load Chronically, as Demonstrated in Vivo. Brain Stimulation, 13, 1014-1023. https://doi.org/10.1016/j.brs.2020.03.016 |
| [7] | Chen, S., Tsai, C., Lin, C., Lee, C., Yu, H., Hsieh, T., et al. (2020) Transcranial Focused Ultrasound Pulsation Suppresses Pentylenetetrazol Induced Epilepsy in Vivo. Brain Stimulation, 13, 35-46. https://doi.org/10.1016/j.brs.2019.09.011 |
| [8] | Jerusalem, A., Al-Rekabi, Z., Chen, H., Ercole, A., Malboubi, M., Tamayo-Elizalde, M., et al. (2019) Electrophysiological-Mechanical Coupling in the Neuronal Membrane and Its Role in Ultrasound Neuromodulation and General Anaesthesia. Acta Biomaterialia, 97, 116-140. https://doi.org/10.1016/j.actbio.2019.07.041 |
| [9] | Yoo, S., Mittelstein, D.R., Hurt, R.C., Lacroix, J. and Shapiro, M.G. (2022) Focused Ultrasound Excites Cortical Neurons via Mechanosensitive Calcium Accumulation and Ion Channel Amplification. Nature Communications, 13, Article No. 493. https://doi.org/10.1038/s41467-022-28040-1 |
| [10] | Taylor, G.J., Heberle, F.A., Seinfeld, J.S., Katsaras, J., Collier, C.P. and Sarles, S.A. (2017) Capacitive Detection of Low-Enthalpy, Higher-Order Phase Transitions in Synthetic and Natural Composition Lipid Membranes. Langmuir, 33, 10016-10026. https://doi.org/10.1021/acs.langmuir.7b02022 |
| [11] | Rezai, A.R., Ranjan, M., D’Haese, P., Haut, M.W., Carpenter, J., Najib, U., et al. (2020) Noninvasive Hippocampal Blood-Brain Barrier Opening in Alzheimer’s Disease with Focused Ultrasound. Proceedings of the National Academy of Sciences, 117, 9180-9182. https://doi.org/10.1073/pnas.2002571117 |
| [12] | Park, S.H., Baik, K., Jeon, S., Chang, W.S., Ye, B.S. and Chang, J.W. (2021) Extensive Frontal Focused Ultrasound Mediated Blood-Brain Barrier Opening for the Treatment of Alzheimer’s Disease: A Proof-of-Concept Study. Translational Neurodegeneration, 10, Article No. 44. https://doi.org/10.1186/s40035-021-00269-8 |
| [13] | Rezai, A.R., Ranjan, M., Haut, M.W., Carpenter, J., D’Haese, P., Mehta, R.I., et al. (2023) Focused Ultrasound-Mediated Blood-Brain Barrier Opening in Alzheimer’s Disease: Long-Term Safety, Imaging, and Cognitive Outcomes. Journal of Neurosurgery, 139, 275-283. https://doi.org/10.3171/2022.9.jns221565 |
| [14] | D’Haese, P., Ranjan, M., Song, A., Haut, M.W., Carpenter, J., Dieb, G., et al. (2020) β-Amyloid Plaque Reduction in the Hippocampus after Focused Ultrasound-Induced Blood-Brain Barrier Opening in Alzheimer’s Disease. Frontiers in Human Neuroscience, 14, Article ID: 593672. https://doi.org/10.3389/fnhum.2020.593672 |
| [15] | Rezai, A.R., D’Haese, P., Finomore, V., Carpenter, J., Ranjan, M., Wilhelmsen, K., et al. (2024) Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer’s Disease. New England Journal of Medicine, 390, 55-62. https://doi.org/10.1056/nejmoa2308719 |
| [16] | Meng, Y., Goubran, M., Rabin, J.S., McSweeney, M., Ottoy, J., Pople, C.B., et al. (2023) Blood-Brain Barrier Opening of the Default Mode Network in Alzheimer’s Disease with Magnetic Resonance-Guided Focused Ultrasound. Brain, 146, 865-872. https://doi.org/10.1093/brain/awac459 |
| [17] | Jeong, H., Im, J.J., Park, J., Na, S., Lee, W., Yoo, S., et al. (2021) A Pilot Clinical Study of Low-Intensity Transcranial Focused Ultrasound in Alzheimer’s Disease. Ultrasonography, 40, 512-519. https://doi.org/10.14366/usg.20138 |
| [18] | Zhang, M., Li, B., Lv, X., Liu, S., Liu, Y., Tang, R., et al. (2021) Low-Intensity Focused Ultrasound-Mediated Attenuation of Acute Seizure Activity Based on EEG Brain Functional Connectivity. Brain Sciences, 11, Article No. 711. https://doi.org/10.3390/brainsci11060711 |
| [19] | Lin, Z., Meng, L., Zou, J., Zhou, W., Huang, X., Xue, S., et al. (2020) Non-Invasive Ultrasonic Neuromodulation of Neuronal Excitability for Treatment of Epilepsy. Theranostics, 10, 5514-5526. https://doi.org/10.7150/thno.40520 |
| [20] | Robinson, M., Lou, J., Mehrazma, B., Rauk, A., Beazely, M. and Leonenko, Z. (2021) Pseudopeptide Amyloid Aggregation Inhibitors: In Silico, Single Molecule and Cell Viability Studies. International Journal of Molecular Sciences, 22, Article No. 1051. https://doi.org/10.3390/ijms22031051 |
| [21] | Nicodemus, N.E., Becerra, S., Kuhn, T.P., Packham, H.R., Duncan, J., Mahdavi, K., et al. (2019) Focused Transcranial Ultrasound for Treatment of Neurodegenerative Dementia. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 5, 374-381. https://doi.org/10.1016/j.trci.2019.06.007 |
| [22] | Deveney, C.M., Surya, J.R., Haroon, J.M., Mahdavi, K.D., Hoffman, K.R., Enemuo, K.C., et al. (2024) Transcranial Focused Ultrasound for the Treatment of Tremor: A Preliminary Case Series. Brain Stimulation, 17, 35-38. https://doi.org/10.1016/j.brs.2023.12.007 |
| [23] | Sung, C., Chiang, P., Tsai, C. and Yang, F. (2021) Low-Intensity Pulsed Ultrasound Enhances Neurotrophic Factors and Alleviates Neuroinflammation in a Rat Model of Parkinson’s Disease. Cerebral Cortex, 32, 176-185. https://doi.org/10.1093/cercor/bhab201 |
| [24] | Wang, B., Chen, M., Chen, S., Feng, X., Liao, Y., Zhao, Y., et al. (2022) Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex. Neural Plasticity, 2022, Article ID: 6472475. https://doi.org/10.1155/2022/6472475 |
| [25] | Liao, Y., Wang, B., Chen, M., Liu, Y. and Ao, L. (2021) LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV-KCC2 Pathway in the L4-L5 Section of the Spinal Cord. Neural Plasticity, 2021, Article ID: 6659668. https://doi.org/10.1155/2021/6659668 |
| [26] | Wang, F., Cai, Q., Ju, R., Wang, S., Liu, L., Pan, M., et al. (2023) Low-Intensity Focused Ultrasound Ameliorates Depression-Like Behaviors Associated with Improving the Synaptic Plasticity in the Vca1-Mpfc Pathway. Cerebral Cortex, 33, 8024-8034. https://doi.org/10.1093/cercor/bhad095 |
| [27] | Sanguinetti, J.L., Hameroff, S., Smith, E.E., Sato, T., Daft, C.M.W., Tyler, W.J., et al. (2020) Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans. Frontiers in Human Neuroscience, 14, Article No. 52. https://doi.org/10.3389/fnhum.2020.00052 |
| [28] | Zou, J., Meng, L., Lin, Z., Qiao, Y., Tie, C., Wang, Y., et al. (2020) Ultrasound Neuromodulation Inhibits Seizures in Acute Epileptic Monkeys. iScience, 23, Article ID: 101066. https://doi.org/10.1016/j.isci.2020.101066 |
| [29] | Chu, P., Huang, C., Chang, P., Chen, R., Chen, K., Hsieh, T., et al. (2023) Weak Ultrasound Contributes to Neuromodulatory Effects in the Rat Motor Cortex. International Journal of Molecular Sciences, 24, Article No. 2578. https://doi.org/10.3390/ijms24032578 |
| [30] | Riis, T.S., Webb, T.D. and Kubanek, J. (2022) Acoustic Properties across the Human Skull. Ultrasonics, 119, Article ID: 106591. https://doi.org/10.1016/j.ultras.2021.106591 |
| [31] | Kong, C., Park, S.H., Shin, J., Baek, H.G., Park, J., Na, Y.C., et al. (2021) Factors Associated with Energy Efficiency of Focused Ultrasound through the Skull: A Study of 3D-Printed Skull Phantoms and Its Comparison with Clinical Experiences. Frontiers in Bioengineering and Biotechnology, 9, Article ID: 783048. https://doi.org/10.3389/fbioe.2021.783048 |
| [32] | Legon, W., Adams, S., Bansal, P., Patel, P.D., Hobbs, L., Ai, L., et al. (2020) A Retrospective Qualitative Report of Symptoms and Safety from Transcranial Focused Ultrasound for Neuromodulation in Humans. Scientific Reports, 10, Article No. 5573. https://doi.org/10.1038/s41598-020-62265-8 |
