Deep gray matter iron and disease progression in multiple sclerosis

项目总结 父母资助的总体目标是确定多发性硬化症的进展是否与 与铁相关的灰质深层少突胶质细胞功能障碍。候选人的研究解决了以下问题之一 父母赠款方法的最大局限性，即所涉继承人的共同依赖性-- 关于髓鞘的门铁成像指标以及由此产生的关于特定研究解释的不确定性 结果。这项研究将探索一种先进的多参数分析方法，该方法是由CANDI公司开发的。 改善铁的结果测量的特异性的日期。这项研究将调查三个假设- SES：(I)脱髓鞘增加了父母授予中代理铁标记的实质性变化；(Ii)分离 铁和髓鞘的贡献将在患者中产生更大的铁下降测量；以及(Iii)存在联系 同一地区的铁丢失和脱髓鞘之间的关系。前两个假设的基本原理是： 脱髓鞘对铁指标的基础作用抵消了铁损失的影响，降低了敏感性。 导致铁流失。第三个假说的基本原理是，含铁的少突胶质细胞也对 可形成髓鞘的。研究培训方案有三个里程碑：(一)分析的调整 针对母基金中使用的特定成像指标的方法，(Ii)该方法的应用和统计- CAL分析类似于父母资助的研究，以及(Iii)结果和方法的公布。糖果- Date的职业目标是成为一名兼具教学和研究职责的生物医学教师。 领带。该候选人目前正处于博士后职业生涯阶段。迈向坎迪的下一个职业阶段- Date的目标是成为博士后研究员。一项为期2.5年的职业发展计划旨在促进候选人的 有能力从事研究和教学工作。该计划包括扩大候选人的 掌握临床神经学应用和解释高级成像方法和Pre。 根据所产生的研究结果，减少研究生奖学金的提交。培训计划 具体解决候选人面临的独特挑战和典型障碍 大多数实习生都会遇到。PI是候选人的主要导师，并由一个团队提供支持 在与候选人未来职业相关的互补主题领域拥有专业知识的共同导师。

PROJECT SUMMARY The overall objective of the parent grant is to determine whether the progression of multiple sclerosis is linked to iron-related oligodendroglia dysfunction in the deep gray matter. The candidate research addresses one of the most significant limitations of the parent grant methodology, i.e., the co-dependence of the involved surro- gate iron imaging metrics on myelin and the resulting uncertainty concerning the interpretation of specific study outcomes. The research will explore an advanced multi-parametric analysis approach developed by the candi- date to improve the specificity of outcome measures toward iron. The research will investigate three hypothe- ses: (i) demyelination adds substantial variation to the surrogate iron marker in the parent grant; (ii) separation of iron and myelin contributions will yield greater iron decline measurements in patients; and (iii) a link exists between iron loss and demyelination in the same region. The rationale for the first two hypotheses is that con- founding effects of demyelination on the iron metrics counteract the effects of iron loss, reducing the sensitivity toward iron loss. The rationale for the third hypothesis is that iron-containing oligodendrocytes are also respon- sible for myelination. The research training program has three milestones: (i) adjustment of the analysis method toward the specific imaging metrics used in the parent grant, (ii) application of the method and statisti- cal analysis analogously to the parent grant research, and (iii) publication of results and methods. The candi- date’s career goal is to become a faculty in biomedical sciences with both teaching and research responsibili- ties. The candidate is currently at the predoctoral career stage. The following career stage toward the candi- date’s goal will be a postdoctoral fellow. A 2.5-years career development plan aims to further the candidate’s ability to pursue a career in research and teaching. The plan includes objectives to expand the candidate’s skillset toward the clinical neurological application and interpretation of advanced imaging methods and pre- pare postgraduate fellowship award submissions based on the research results generated. The training plan specifically addresses both unique challenges faced by the candidate and typical barriers and impediments encountered by most trainees. The PI serves as the candidate’s primary mentor and is supported by a team of co-mentors with expertise in complementary topic areas relevant for the candidate’s future career.