Supplementary Material for: The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot’s targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim’s circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.

特发性震颤（Essential Tremor, ET）是最为常见的运动障碍性疾病。目前，药物难治性震颤的金标准治疗方案为脑深部电刺激，其次为射频毁损术。伽玛刀（Gamma Knife, GK）立体定向放射外科则被视为微创替代治疗手段。绝大多数此类手术的靶点均为丘脑腹中间核（thalamic ventro-intermediate nucleus, Vim）。
本研究的核心目的为评估临床疗效与神经影像学改变的相关性，涵盖结构与功能两个层面。本中心所有伽玛刀治疗均统一采用Guiot定位方法，辐射剂量设定为130 Gy。本次研究的磁共振神经影像学方案包含结构成像（T1加权成像（T1-weighted imaging）、弥散加权成像（diffusion-weighted imaging, DWI））、静息态功能磁共振成像（resting-state functional MRI），以及18F-氟代脱氧葡萄糖正电子发射断层扫描（18F-fluorodeoxyglucose-positron emission tomography）。
神经影像学改变的分析将从两个维度展开：其一，基于丘脑腹中间核的神经环路假说，针对小脑-丘脑-皮质通路（cerebello-thalamo-cortical tract），涉及运动皮层、同侧丘脑腹中间核及对侧小脑齿状核；其二为全脑层面的无预设假说分析。
本研究方案旨在借助现代神经影像学技术，探究丘脑腹中间核伽玛刀放射外科的放射生物学特性及其与临床疗效的关联，尤其聚焦于特发性震颤患者。从长远来看，依托此类研究方法，患者筛选可基于特定的脑连接组特征进行。