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

用于癌症样本分子分析的多模态 X 射线透射和衍射扫描仪

• 批准号: 10656798
• 负责人: Joel Greenberg
• 金额: $ 27.2万
• 依托单位: QUADRIDOX, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10656798
• 关键词: 3-Dimensional; Address; Anatomy; Architecture; Biological; Biological Markers; Breast; Clinical; Clinical Research; Code; Contrast Media; Crystallography; Custom; Dehydration; Disease; Disease Progression; Ensure; Environment; Evolution; Exhibits; Hour; Image; Imaging Device; Laboratories; Laboratory Research; Legal patent; Length; Malignant Bone Neoplasm; Malignant Neoplasms; Measurement; Measures; Methods; Molecular; Molecular Analysis; Molecular Structure; Morphology; Multimodal Imaging; Operative Surgical Procedures; Pathology; Pathway interactions; Performance; Play; Positron-Emission Tomography; Preparation; Property; Protocols documentation; Research Personnel; Resolution; Roentgen Rays; Role; Rotation; Sampling; Scanning; Source; Specificity; Specimen; Stains; Structure; Surface; Synchrotrons; System; Techniques; Technology; Testing; Thick; Three-Dimensional Imaging; Tissues; Work; X ray diffraction analysis; X-Ray Medical Imaging; anticancer research; base; bone; bone imaging; cancer biomarkers; cell type; design; high resolution imaging; imaging biomarker; imaging modality; imaging software; innovation; insight; malignant breast neoplasm; microCT; millimeter; multimodality; performance tests; prototype; radiological imaging; reconstruction; single photon emission computed tomography; soft tissue; tissue preparation; tomography; tool; transmission process; tumor; user-friendly

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.

抽象的 使用BiosCimens进行癌症研究需要分析具有较大尺寸（sub-mm至cm）和分子组成的样品，并在较大的长度尺度上进行分析。在许多情况下，有关标本的三维空间信息对于理解和解决疾病进展至关重要。 X射线成像已被广泛认可在组织分析和癌症评估中起关键作用。虽然在某些应用与疾病状态高度相关的某些应用中已成功使用了传输X射线成像（放射线照相或CT），但它缺乏分子特异性，这限制了其在样品分析中的一般效用。许多小组已经证明了X射线衍射（XRD）在分析生物测量中的分子结构中的实用性。但是，在实验室环境中，没有人成功实施了一种可行的3D XRD测量方法的可行方法。与实现这种系统有关的关键挑战包括高精度XRD测量通常需要访问同步加速器或其他专用来源，这对于普通研究人员来说很难访问。相反，常规实验室衍射方法缓慢，需要破坏或改变样品，并且显示出较差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放射线照相成像设备，该设备可以扫描生物测量的全部体积并生成共同注册的多模式X射线传输和XRD图像。这种技术将使研究人员能够使用紧凑，健壮且易于访问的工具在平均研究实验室中研究具有高空间分辨率和高特异性的组织样品的分子特性。在没有对比剂的情况下，将对样品进行分析，几乎不需要样品制备。通过以前的工作，我们已经建立，测试并证明了生物测量组合传输和衍射成像所需的基本技术。现在，我们将构建扫描仪的临床上可访问的高分辨率原型，测试和验证其性能，并证明其在成像骨和乳腺癌生物测量方面的实用性。该项目将提供对癌症生物测量的非破坏性分析的首个X射线传播/衍射扫描仪，这可以为探索XRD在组织异常中的作用的新临床研究提供途径，最终导致对癌症的发生和进化的了解更好。