In vivo imaging of cortical porosity in the peripheral skeleton

描述（由申请人提供）：这是 Galateia Kazakia 博士的 K01 奖励提案；加州大学旧金山分校博士后研究员。该 K01 奖项将为 Kazakia 博士提供实现以下目标所需的支持：1）成为临床导向的骨质量成像研究专家； 2）开发皮质骨微结构体内成像工具和技术； 3) 对人类受试者皮质大孔隙的发生、进展和后果进行临床研究； 4）获得临床研究、肌肉骨骼疾病和统计方法方面的培训； 5）发展独立的研究事业。为了实现这些目标，Kazakia 博士组建了一个指导团队，成员包括： Sharmila Majumdar 博士（主要导师），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模式开发和应用专家； Deborah Sellmeyer，医学博士，加州大学旧金山分校骨质疏松症中心主任，在临床骨质疏松症研究方面拥有丰富的经验； Thomas Lang 博士，QCT 图像采集和处理专家；陆瑛博士，加州大学旧金山分校放射学生物统计学组主任；南希·莱恩 (Nancy Lane) 医学博士，加州大学戴维斯分校医学中心医学和风湿病学教授。 随着能够可视化骨骼微观结构的高分辨率非侵入性成像技术的发展，在骨质减少人群中发现了大皮质“宏观孔隙”的证据。虽然这种大孔隙的生物力学影响可能很大，但有关其发生率的报道只是轶事，其形态特征尚未确定，其病因尚不清楚。本提案的目的是开发用于高分辨率外周 QCT (HR-pQCT) 数据中皮质大孔隙结构表征的工具，并研究人类受试者中皮质大孔隙的发生率、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 图像中的皮质宏观孔隙度。在目标 2 中，将对健康受试者和骨质减少受试者的宏观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，以确定宏观孔隙率参数是否可以将患有脆性骨折的女性与对照组区分开来。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 培训期的最后阶段在 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.