Advanced MR Imaging and Image Analytics as a Precision Medicine Tool to Manage ADPKD

摘要 NIDDK导师研究科学家发展奖的目标是提供一个有组织的科学 和教育环境，让蒂莫西·克莱恩博士开始他的独立研究生涯 专注于开发腹部器官的新成像技术和图像分析技术 病理学。这份提案概述了梅奥诊所的一个五年培训计划，该计划的主要导师是Dr。 布拉德利·埃里克森和一个由以下领域的资深研究人员组成的指导团队：生物学， 肾病学、遗传学、放射学、信息学；医学物理学、生物统计学、图像处理和生理学。 这项建议的重点是改善常染色体显性遗传的研究和疾病预后。 多囊肾病(ADPKD)患者通过生物医学成像技术。众所周知， 影像对于ADPKD的诊断、监测和预后预测是必不可少的。临床研究使用总 肾体积(TKV)(由MRI作为基于图像的生物标志物测量)以跟踪进展 ADPKD，因为在人类和动物模型中，较大的TKV被证明与较差的预后相关 学习。然而，使用TKV作为疾病进展的标志也存在挑战。首先，这是一个 简化了疾病状态，并且不告知涉及到的微观疾病过程 对健康肾组织的零星破坏。此外，测量TKV既耗时又昂贵， 而且标准化程度不高。引入测量TKV的自动化方法将大大改善： 测量吞吐量，显著降低与执行研究研究相关的成本，允许 在机构内部和跨机构获得准确和可重复的测量；促进 寻找新的影像生物标志物。该项目的具体目标是：(I)开发和验证自动化 表征肾脏结构的工具，如TKV和囊性负荷；(Ii)探索新的成像生物标记物 图像纹理特征分析和模式识别技术；以及(Iii)开发一种新技术来 测量肾脏血流量。这项研究将得到梅奥诊所出色的临床和研究的推动 致力于改善患者护理的环境，以及梅奥诊所翻译PKD中心，它 重点将基础科学研究转化为改善ADPKD的管理和治疗 病人。克莱恩博士在成像技术和图像处理方面的背景使他特别适合 来进行这项研究。除了上述目标，克莱恩博士还将：1)在以下领域建立强大的知识基础 通过参加相关的查房、研讨会和国家会议，包括肾病学和放射学；2)加强 他在医学成像、生物学、生理学、遗传学和编程方面的知识，通过课程和 指导；3)参加以拨款和出版物写作为重点的研讨会；4)提交极具竞争力的 R01应用程序在本研究提案的基础上进行扩展。这项提议将导致 改进了当前的分析工作流程，并更好地了解了 ADPKD新的影像生物标志物。获得这一K奖将极大地促进克莱恩博士向 自主研究事业兴旺。

ABSTRACT The goal of this NIDDK Mentored Research Scientist Development Award is to provide an organized scientific and educational environment for Dr. Timothy Kline to begin his transition into an independent research career focused on developing novel imaging technologies and image analysis techniques for abdominal organ pathologies. This proposal outlines a five-year training plan at Mayo Clinic under the primary mentorship of Dr. Bradley Erickson and a Mentoring Team comprised of accomplished researchers in the fields of: biology, nephrology, genetics, radiology, informatics; medical physics, biostatistics, image processing, and physiology. The focus of this proposal is to improve both research studies and disease prognosis for autosomal dominant polycystic kidney disease (ADPKD) patients through biomedical imaging techniques. It is well understood that imaging is essential for ADPKD diagnosis, monitoring, and outcome prediction. Clinical studies utilize total kidney volume (TKV) (as measured by MRI as an image-based biomarker) to follow the progression of ADPKD, as larger TKVs have been shown to correlate with worse prognosis in both human and animal-model studies. However, there are challenges with using TKV as a marker of disease progression. For one, it is a simplification of the disease state and does not inform on microscopic disease processes that are involved with piecemeal destruction of healthy renal tissue. In addition, measurements of TKVs are time consuming, costly, and poorly standardized. The introduction of automated approaches for measuring TKV will: greatly improve measurement throughput, significantly reduce costs associated with performing research studies, allow accurate and reproducible measurements to be obtained both within and across institutions; facilitate the search for new imaging biomarkers. The specific aims of this project are to: (i) develop and validate automated tools to characterize renal structure, such as TKV and cystic burden; (ii) explore new imaging biomarkers by image texture feature analysis and pattern recognition techniques; and (iii) develop a new technique to measure renal blood flow. This research will be facilitated by Mayo Clinic's outstanding clinical and research environment dedicated to improving patient care, as well as the Mayo Clinic Translational PKD Center, which focuses on translating basic science research into improvements in the management and treatment of ADPKD patients. Dr. Kline's background in imaging technologies and image processing makes him particularly suited to perform this research. In addition to the above aims, Dr. Kline will: 1) develop a strong knowledge base in both nephrology and radiology by attending relevant rounds, seminars, and national conferences; 2) enhance his knowledge of medical imaging, biology, physiology, genetics, and programming through coursework and mentoring; 3) attend workshops focused on grant and publication writing; and 4) submit a highly competitive R01 application expanding upon the findings from this research proposal. This proposal will lead to vast improvements to current analysis workflows, as well as an improved understanding of the prognostic power of new imaging biomarkers of ADPKD. Obtaining this K Award will greatly facilitate Dr. Kline's transition into a prosperous independent research career.