In vivo imaging of cortical porosity in the peripheral skeleton

描述(由申请人提供)：这是一份K01奖项建议书，授予加州大学旧金山分校博士后研究员Galateia Kazaki博士。K01奖项将为Kazaki博士提供必要的支持，以实现以下目标：1)成为临床骨质量成像研究的专家；2)开发皮质骨微观结构的活体成像工具和技术；3)对人类受试者皮质微孔率的发生、发展和后果进行临床调查；4)接受临床研究、肌肉骨骼疾病和统计学方法方面的培训；以及5)发展独立的研究事业。为了实现这些目标，Kazaki博士组建了一支指导团队，成员包括：加州大学旧金山分校肌肉骨骼定量成像研究小组主任、肌肉骨骼系统先进成像方法开发和应用专家Sharmila Majudar博士(主要导师)、加州大学戴维斯分校骨质疏松中心主任Deborah Sellmeyer医学博士、量化CT图像采集和处理专家Thomas Lang博士、加州大学戴维斯医学中心医学和瘤热学教授Ying Lu博士。 随着能够可视化骨骼微结构的高分辨率非侵入性成像技术的发展，在骨量减少的人群中发现了大量的皮质“大孔洞”的证据。虽然这种巨大孔洞的生物力学影响可能很大，但关于其发生的报道只是轶事，其形态尚未确定，其病因尚不清楚。这项建议的目的是开发工具来表征高分辨率外周QCT(HR-pQCT)数据中的皮质大孔率的结构特征，并调查受试者皮质大孔率的发生率、进展和后果。在目标1中，将开发图像处理工具和定量3D结构测量来表征HR-pQCT图像中的大脑皮层大孔率。在目标2中，将对健康受试者和骨量减少受试者的大孔隙度测量进行量化和比较。在目标3中，将进行一项横断面研究，以确定宏观孔隙度参数是否可以区分脆性骨折妇女和对照组。这项研究将构成前瞻性骨折风险评估研究的基础，该研究将在K01训练期最后阶段的R01拨款申请中提出。

DESCRIPTION (provided by applicant): This is a K01 award proposal for Galateia Kazakia, Ph.D; a postdoctoral fellow at the University of California, San Francisco. This K01 award will provide Dr. Kazakia with the support necessary to accomplish the following goals: 1) to become an expert in clinically oriented bone quality imaging research; 2) to develop tools and techniques for in vivo imaging of cortical bone micro-structure; 3) to conduct a clinical investigation of the incidence, progression, and consequence of cortical marco-porosity in human subjects; 4) to obtain training in clinical research, musculoskeletal diseases and statistical methods; and 5) to develop an independent research career. To achieve these goals, Dr. Kazakia has assembled a mentoring team composed of: Sharmila Majumdar, Ph.D (primary mentor), Director of UCSF Musculoskeletal Quantitative Imaging Research Group and expert in development and application of advanced imaging modalities to the musculoskeletal system; Deborah Sellmeyer, M.D., who as Director of UCSF Center for Osteoporosis has extensive experience in clinical osteoporosis research; Thomas Lang, Ph.D, an expert in QCT image acquisition and processing; Ying Lu, Ph.D., Director of the UCSF Biostatistics in Radiology group; and Nancy Lane, M.D., Professor of Medicine and Rheumatology at the UC Davis Medical Center. With the development of high resolution non-invasive imaging techniques capable of visualizing skeletal micro-structure, evidence of large cortical "macro-porosity" has been found in osteopenic populations. While the biomechanical impact of this macro-porosity is likely to be great, reports of its incidence are anecdotal, its morphology is not characterized, and its etiology is unknown. The objective of this proposal is to develop tools for the structural characterization of cortical macro-porosity in high resolution peripheral QCT (HR-pQCT) data, and to investigate the incidence, progression, and consequence of cortical macro-porosity in human subjects. In Aim 1, image processing tools and quantitative 3D structural measures will be developed to characterize cortical macro-porosity in HR-pQCT images. In Aim 2, macro-porosity measures in healthy and osteopenic subjects will be quantified and compared. In Aim 3, a cross-sectional study will be performed to determine whether macro-porosity parameters can discriminate women with fragility fracture from controls. This research will form the basis for a prospective fracture risk assessment study, to be proposed in an R01 grant application during the final stage of this K01 training period.