Multimodality X-ray transmission and diffraction scanner for molecular analysis of cancer specimens

摘要 使用生物标本的癌症研究需要分析具有大范围尺寸（亚毫米到厘米）和分子组成的样品，其长度范围很广。在许多情况下，关于标本的三维空间信息对于理解和解决疾病的进展至关重要。X射线成像已被广泛认为在组织分析和癌症评估中发挥关键作用。虽然透射X射线成像（射线照相术或CT）已成功地用于其中样品形态与疾病状态高度相关的一些应用中，但其缺乏分子特异性，这限制了其在样本分析中的一般效用。许多研究小组已经证明了X射线衍射（XRD）在分析生物样品分子结构中的实用性;然而，没有一个研究小组成功地在实验室环境中实施了快速准确的3D XRD测量的可行方法。与实现这样一个系统相关的关键挑战包括这样一个事实，即高精度XRD测量通常需要使用同步加速器或其他专用源，这对于普通研究人员来说是很难访问的。相比之下，传统的实验室衍射方法是缓慢的，需要破坏或改变的标本，并表现出穷人或没有体积的空间信息。为了克服这些挑战，我们建议开发一种新的射线照相成像设备，可以扫描整个体积的生物标本，并生成共注册，多模态X射线透射和XRD图像。这种技术将使研究人员能够使用一种紧凑、坚固且在普通研究实验室中易于获得的工具，以高空间分辨率和高特异性研究组织标本的分子特性。将在没有造影剂的情况下分析样本，并且几乎不需要样本制备。通过以前的工作，我们已经建立，测试，并证明了所需的基础技术相结合的传输和衍射成像的生物标本。我们现在将建立一个临床上可访问的，高分辨率的扫描仪原型，测试和验证其性能，并证明其在成像骨和乳腺癌生物标本的实用性。该项目将为癌症生物标本的非破坏性分析提供首个X射线透射/衍射扫描仪，这可能为探索XRD在组织异常中的作用的新临床研究提供途径，最终导致更好地了解癌症的起源和演变。

ABSTRACT Cancer research using biospecimens requires the analysis of samples with a large range of sizes (sub-mm to cm) and molecular composition over a wide range of length scales. In many cases, 3-dimensional spatial information about the specimen is critical to understanding and addressing the progression of the disease. X-ray imaging has been widely recognized to play a key role in tissue analysis and cancer assessment. While transmission X-ray imaging (radiography or CT) has been used successfully in some applications wherein sample morphology is highly correlated with the disease state, it lacks molecular specificity, which limits its general utility in specimen analysis. Many groups have demonstrated the utility of X-ray diffraction (XRD) in analyzing molecular structure in biospecimens; however, none have successfully implemented a viable method of fast and accurate 3D XRD measurement in a laboratory environment. The key challenges associated with realizing such a system include the fact that high accuracy XRD measurements have typically required access to a synchrotron or another specialized source, which is difficult for the average researcher to access. In contrast, conventional laboratory diffraction methods are slow, require destruction or alteration of the specimens, and exhibit poor or no volumetric spatial information. To overcome these challenges, we propose to develop a new radiographic imaging device that can scan the entire volume of a biospecimen and generate co-registered, multi-modal X-ray transmission and XRD images. Such technology would allow researchers to study molecular properties of tissue specimens with high spatial resolution and high specificity using a tool that is compact, robust, and easily accessible in an average research laboratory. The samples would be analyzed without contrast agents and with little to no sample preparation required. Through previous work, we have built, tested, and demonstrated the underlying technology required for combined transmission and diffraction imaging of biospecimens. We will now build a clinically accessible, high-resolution prototype of the scanner, test and validate its performance, and demonstrate its utility in imaging bone and breast cancer biospecimens. This project will provide a first-of-its-kind X-ray transmission/diffraction scanner for non-destructive analysis of cancer biospecimens, which could enable pathways for new clinical studies exploring the role of XRD in tissue abnormalities, eventually leading to a better understanding of the genesis and evolution of cancer.