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

摘要

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.