Improving white matter integrity with thyroid hormone

项目总结/摘要 促进和支持髓鞘再生的能力对许多神经系统疾病具有广泛的意义。 从多发性硬化症到重度抑郁症的神经精神疾病。临床前证据表明， 证明甲状腺激素治疗，以三碘甲状腺原氨酸（T3）或四碘甲状腺原氨酸（T4）的形式， 可通过增加髓鞘碱性蛋白mRNA和蛋白、少突胶质细胞 增殖和成熟以及部分各向异性（白色物质完整性的扩散成像测量）。 我们自己研究的初步数据表明，基线甲状腺状态与白色的完整性相关。 与严重抑郁症有关的物质束迄今为止，甲状腺激素给药对白色 物质束尚未在成年人体内进行研究。拟议试点研究的目的是 使用高角度扩散成像和多组分成像检查白色物质束完整性的变化 在临床上需要接受甲状腺激素治疗甲状腺功能减退症的受试者人群中进行松弛测量。我们 将在治疗开始时以及开始后3个月和6个月对甲状腺功能减退症患者进行扫描， 甲状腺激素治疗我们还将管理评估情绪和认知的量表， 显示与白色物质完整性相关。我们假设甲状腺激素治疗 与分数各向异性的增加，径向扩散率的降低和 髓鞘水部分（髓鞘形成改善的标志物），其将与认知的改善相关， 情绪评分如果成功，这将是第一次证明改善甲状腺白色物质的完整性 激素替代，并为旨在恢复大脑结构连接的治疗铺平道路。

PROJECT SUMMARY/ABSTRACT The ability to promote and support remyelination has wide-ranging implications for a number of neuropsychiatric conditions from multiple sclerosis to major depression. Pre-clinical evidence has demonstrated that thyroid hormone treatment, in the form of triiodothyronine (T3) or tetraiodothyronine (T4), can promote and support remyelination by increasing myelin basic protein mRNA and protein, oligodendrocyte proliferation and maturation, and fractional anisotropy (a diffusion imaging measure of white matter integrity). Pilot data from our own studies suggest that baseline thyroid status is correlated with the integrity of white matter tracts associated with major depression. To date, the impact of thyroid hormone administration on white matter tracts has not been studied in vivo in adult humans. The purpose of the proposed pilot study is to examine changes in white matter tract integrity using high angular diffusion imaging and multi-component relaxometry in a population of subjects clinically indicated to receive thyroid hormone for hypothyroidism. We will scan patients with hypothyroidism at the initiation of treatment and at three and six months after starting thyroid hormone treatment. We will also administer scales assessing mood and cognition which have been shown to correlate with white matter integrity. We hypothesize that thyroid hormone treatment will be associated with an increase in fractional anisotropy, a decrease in radial diffusivity, and an increase in the myelin water fraction (markers of improved myelination) that will correlate with improvements in cognition and mood ratings. If successful, this will be the first demonstration of improved white matter integrity with thyroid hormone replacement and pave the way for therapies designed to restore structural brain connectivity.