SUB-MICRON X-RAY TOMOGRAPHY OF CALCIFIED TISSUE

描述（改编自申请人摘要）：钙沉淀 在人体组织中作为骨、牙齿形成的一部分，或在某些 异常过程（即，如良性或恶性钙化 乳房、血管斑块、肾或胆囊中形成的结石等）。 在骨骼中，组织形成有复杂的等级结构， 产生定向材料特性。 传统的显微镜方法是 不适合研究这种三维（3-D）结构，因为 光和高能电子对矿化物质的渗透最小， 组织. 能量范围从7到11 keV的X射线穿透小 钙化组织样本，尺寸为50至250微米， 可以允许测量的3-D分布的特性， 矿物浓度，分辨率为0.1至0.5微米。 3D X射线显微断层摄影术是一种方法，其中， 从不同方向采集样品并重建数据 用计算机产生一个数组（512 x 512 x 256）的值比例 在许多位置的样品的X射线衰减系数。 使用微焦点X射线管的方法经常被用于研究骨 样本尺寸范围为4至20 mm，分辨率为25至125 微米 使用同步加速器X射线源的显微层析成像能够 更好的分辨率，但检测器的局限性限制了目前的方法， 分辨率为2至25微米。 申请人提出研究一种方法，该方法使用来自 同步加速器源（先进光子源，APS，在阿贡国家 实验室），其可实现0.1至0.5微米的分辨率。 一个 使用波带片将X射线束聚焦到 提出了亚微米光斑。 该方法结合了为以下目的开发的方法： 使用较低X射线能量的扫描X射线显微术和方法 用于使用电子束的锥形束层析成像的层析成像重建 X射线源 将使用湿骨标本评价所开发的方法。 的 用胶原基质确定三维超微结构的能力， 骨板内矿物质的结构和取向，以及孔隙率 将专门检查骨组织。 如果成功，这种方法 将允许以具有以下分辨率的三维骨骼结构的研究： 以前是不可能的。

DESCRIPTION (Adapted from the applicant's abstract): Calcium precipitates in human tissue as a part of the formation of bone, teeth, or in certain abnormal processes (i.e., such as benign or malignant calcifications of the breast, vascular plaque, stones formed in the kidney or gallbladder, etc.). In bone, tissue is formed with a complex hierarchical structure which produces oriented material properties. Conventional microscopy methods are not suitable for studying this three dimensional (3-D) structure since both light and energetic electrons have minimal penetration into mineralized tissue. X-rays in the energy range from 7 to 11 keV penetrate small calcified tissue specimens of 50 to 250 micrometer dimension with characteristics that may permit measurement of the 3-D distribution of mineral concentration with a resolution of 0.1 to 0.5 micrometer. 3D X-ray microtomography is a method wherein many radiographic views of a specimen are acquired from different direction and the data reconstructed with a computer to produce an array (512 x 512 x 256) of values proportional to the X-ray attenuation coefficient of the specimen at many locations. Methods using microfocus X-ray tubes have been frequently used to study bone specimens with a size ranging from 4 to 20 mm with a resolution of 25 to 125 microns. Microtomography using synchrotron X-ray sources is capable of better resolution but detector limitations have limited present methods to a resolution of 2 to 25 micrometers. The applicant proposes to investigate a method using X-rays from a synchrotron source (the Advanced Photon Source, APS, at Argonne National Laboratory) which might achieve a resolution of 0.1 to 0.5 micrometer. An innovative approach using a zone plate to focus an X-ray beam to a sub-micron spot is proposed. The approach combines methods developed for scanning X-ray microscopy using lower X-ray energies and methods for tomographic reconstruction developed for cone beam tomography using electron beam X-ray sources. The methods developed will be evaluated using wet bone specimens. The ability to determine the 3-D ultrastructure with the collagen matrix, the structure and orientation of mineral within bone lamella, and the porosity of bone tissue will be specifically examined. If successful, this method will permit investigations of 3-D bone structure at a resolution that has previously not been possible.