Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
Neuromodulation. 2020 Jun;23(4):489-495. doi: 10.1111/ner.13120. Epub 2020 Feb 14.
Early clinical trials suggest that deep brain stimulation at kilohertz frequencies (10 kHz-DBS) may be effective in improving motor symptoms in patients with movement disorders. The 10 kHz-DBS can deliver significantly more power in tissue compared to conventional frequency DBS, reflecting increased pulse compression (duty cycle). We hypothesize that 10 kHz-DBS modulates neuronal function through moderate local tissue heating, analogous to kilohertz spinal cord stimulation (10 kHz-SCS). To establish the role of tissue heating in 10 kHz-DBS (30 μs, 10 kHz, at intensities of 3-7 mA ), a decisive first step is to characterize the range of temperature changes during clinical kHz-DBS protocols.
We developed a high-resolution magnetic resonance imaging-derived DBS model incorporating joule-heat coupled bio-heat multi-physics to establish the role of tissue heating. Volume of tissue activated (VTA) under assumptions of activating function (for 130 Hz) or heating (for 10 kHz) based neuromodulation are contrasted.
DBS waveform power (waveform RMS) determined joule heating at the deep brain tissues. Peak heating was supralinearly dependent on stimulation RMS. The 10 kHz-DBS stimulation with 2.3 to 5.4 mA (corresponding to 3 to 7 mA ) produced 0.10 to 1.38°C heating at the subthalamic nucleus (STN) target under standard tissue parameters. Maximum temperature increases were predicted inside the electrode encapsulation layer (enCAP) with 2.3 to 5.4 mA producing 0.13 to 1.87°C under standard tissue parameters. Tissue parameter analysis predicted STN heating was especially sensitive (ranging from 0.44 to 1.35°C at 3.8 mA ) to decreasing enCAP electrical conductivity and decreasing STN thermal conductivity.
Subject to validation with in vivo measurements, neuromodulation through a heating mechanism of action by 10 kHz-DBS can indicate novel therapeutic pathways and strategies for dose optimization.
早期临床试验表明，千赫兹频率（10 kHz-DBS）的深部脑刺激可能有助于改善运动障碍患者的运动症状。与传统频率 DBS 相比，10 kHz-DBS 可以在组织中输送更多的功率，这反映了脉冲压缩（占空比）的增加。我们假设 10 kHz-DBS 通过适度的局部组织加热来调节神经元功能，类似于千赫兹脊髓刺激（10 kHz-SCS）。为了确定组织加热在 10 kHz-DBS（30μs，10 kHz，强度为 3-7 mA）中的作用，决定性的第一步是描述临床 10 kHz-DBS 方案中温度变化的范围。
我们开发了一种高分辨率磁共振成像衍生的 DBS 模型，该模型结合了焦耳热耦合生物热多物理场，以确定组织加热的作用。基于激活函数（130 Hz）或加热（10 kHz）的假设，对比了激活的组织体积（VTA）。
DBS 波形功率（波形 RMS）确定了深部脑组织的焦耳加热。峰值加热与刺激 RMS 呈超线性关系。在标准组织参数下，10 kHz-DBS 刺激 2.3 至 5.4 mA（对应于 3 至 7 mA）可在丘脑底核（STN）靶点产生 0.10 至 1.38°C 的加热。在标准组织参数下，最大温度升高预测在电极封装层（enCAP）内，2.3 至 5.4 mA 产生 0.13 至 1.87°C 的加热。组织参数分析预测 STN 加热对 enCAP 电导率降低和 STN 热导率降低特别敏感（在 3.8 mA 时范围为 0.44 至 1.35°C）。
在经过体内测量验证的前提下，通过 10 kHz-DBS 的加热作用进行神经调节，可以为优化剂量提供新的治疗途径和策略。
