Deep gray matter iron and disease progression in multiple sclerosis

项目摘要 父母补助金的总体目标是确定多发性硬化症的进展是否与 铁相关的少突胶质细胞功能障碍。候选人研究解决了以下问题之一： 父母补助金方法的最大限制，即，参与surro的相互依赖性， 门铁成像指标对髓鞘和由此产生的不确定性有关的解释具体的研究 结果。该研究将探索由candi开发的先进的多参数分析方法， 日期，以提高对铁的结果措施的特异性。本研究将探讨三种假说- ses：（i）脱髓鞘增加了母体补助金中替代铁标记物的实质性变化;（ii）分离 铁和髓磷脂的贡献将产生更大的铁下降测量患者;和（iii）存在联系 同一区域的缺铁和脱髓鞘之间的联系前两个假设的基本原理是， 发现脱髓鞘对铁指标的影响抵消了铁损失的影响，降低了敏感性 铁的损失。第三个假设的基本原理是，含铁少突胶质细胞也对铁的分泌有反应。 可用于髓鞘形成。研究培训计划有三个里程碑：（一）调整分析 方法对父母补助金中使用的特定成像度量，（ii）方法和统计的应用， cal分析类似于母基金研究，和（iii）结果和方法的出版物。坎迪- 日期的职业目标是成为一个教师在生物医学科学与教学和研究的责任， 关系的候选人目前处于博士前职业阶段。接下来的职业生涯阶段走向坎迪- 戴特的目标是博士后研究员。一个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事业。该计划包括扩大候选人的目标 对先进的成像方法和预临床神经学应用和解释的技能， 根据产生的研究成果帕雷研究生奖学金。培训计划 具体解决候选人面临的独特挑战和典型障碍和障碍 大多数学员遇到的。PI作为候选人的主要导师，由以下团队提供支持： 在与候选人未来职业相关的互补主题领域具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.