System Development and Preclinical Applications of Photon Counting Micro-CT

Abstract

X-ray computed tomography (CT) is a powerful multi-dimensional (3D + time or energy) imaging modality lauded for its high temporal and spatial resolution. There have been considerable efforts to expand the modality from an anatomical to a functional one, systems capable of measuring metrics such as cardiac and lung function, receptor expression, or metabolic rate in addition to anatomical morphology. This can be accomplished through temporal and spectral imaging CT imaging, where energy dependent material attenuation allows for quantitative separation. These methods are combined synergistically with novel contrast agents, such as targeted nanoparticle-based contrast agents designed to accumulate in cancerous growths, marking tumor boundaries, and provide therapeutic benefits. Here we set forth work furthering the preclinical imaging capabilities of micro-CT, including the design and validation of new micro-CT imaging systems capable of functional imaging in small animal models. These systems are used for longitudinal in vivo imaging and ex vivo validation studies, including temporally resolved cardiac and respiratory imaging and cancer imaging studies. Additionally, image processing tools are presented for addressing artifacts, improving image quality, and image analysis for the studies performed in a preclinical setting. These tools are based on both conventional image processing and powerful new artificial intelligence methods. They involve correction of spatial and spectral image artifacts, segmentation and detection of tumors, and radiomic analysis of imaging data, and have shown use in automating high-throughput imaging. Our imaging results illustrate that functional micro-CT can further the utility of preclinical imaging. These systems and tool will benefit nanotechnology and cancer research, providing a test bed in which to test and optimize novel imaging methods. The developed micro-CT systems can serve to further research in diagnostic and therapeutic, or theranostics, applications for personalized medicine.