Innovation and fusion of x-ray and optical tomography for mouse studies of breast cancer

For early detection and targeted therapy, receptor expression profiling is instrumental to classifying breast cancer into sub-groups. In particular, human epidermal growth factor receptor 2 (HER2) expression has been shown to have both prognostic and predictive values. Recently, an increasingly more complex view of HER2 in breast cancer has emerged from genome sequencing that highlights the role of inter- and intra-tumor heterogeneity in therapy resistance. Studies on such heterogeneity demand high-content, high-resolution functional and molecular imaging in vivo, which cannot be achieved using any single imaging tool. Clearly, there is a critical need to develop a multimodality approach for breast cancer imaging. Since 2006, grating-based x-ray imaging has been developed for much-improved x-ray images. In 2014, the demonstration of fluorescence molecular tomography (FMT) guided by x-ray grating-based micro-CT was reported with encouraging results and major drawbacks. In this paper, we propose to integrate grating-based x-ray tomography (GXT) and high-dimensional optical tomography (HOT) into the first-of-its-kind truly-fused GXT-HOT (pronounced as “Get Hot”) system for imaging of breast tumor heterogeneity, HER2 expression and dimerization, and therapeutic response. The primary innovation lies in developing a brand-new high-content, high-throughput x-ray optical imager based on several contemporary techniques to have MRI-type soft tissue contrast, PET-like sensitivity and specificity, and micro-CT-equivalent resolution. This system consists of two orthogonal x-ray Talbot-Lau interferometric imaging chains and a hyperspectral time-resolved single-pixel optical imager. Both the system design and pilot results will be reported in this paper, along with relevant issues under further investigation.

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