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 使用生物样本进行癌症研究需要分析各种尺寸（亚毫米到厘米）和各种长度尺度的分子组成的样本。在许多情况下，标本的 3 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着关键作用。虽然透射 X 射线成像（放射线照相或 CT）已成功用于样本形态与疾病状态高度相关的一些应用，但它缺乏分子特异性，这限制了其在样本分析中的一般用途。许多研究小组已经证明了 X 射线衍射 (XRD) 在分析生物样本分子结构方面的实用性；然而，没有人成功地在实验室环境中成功实施快速、准确的 3D XRD 测量的可行方法。实现此类系统的关键挑战包括高精度 XRD 测量通常需要使用同步加速器或其他专用源，而这对于普通研究人员来说很难访问。相比之下，传统的实验室衍射方法速度慢，需要破坏或改变样本，并且表现出较差或没有体积空间信息。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，该设备可以扫描生物样本的整个体积并生成共同配准的多模态 X 射线透射和 XRD 图像。此类技术将使研究人员能够使用紧凑、稳健且易于在普通研究实验室中使用的工具，以高空间分辨率和高特异性研究组织样本的分子特性。无需造影剂即可分析样品，并且几乎不需要样品制备。通过之前的工作，我们已经构建、测试并演示了生物样本组合透射和衍射成像所需的基础技术。我们现在将构建一个临床上可用的高分辨率扫描仪原型，测试和验证其性能，并展示其在骨骼和乳腺癌生物样本成像中的实用性。该项目将提供首创的 X 射线透射/衍射扫描仪，用于癌症生物样本的无损分析，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，最终导致更好的结果。了解癌症的起源和进化。