X-ray/optical tomographic guidance and assessment for pre-clinical radiation Research

Ut Southwestern Medical Center, Dallas TX

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY/ABSTRACT Our field is rich with new opportunities to refine the use of radiotherapy(RT). The integration of RT with immunotherapy(IT) holds transformative potential for cancer treatment, yet clinical outcomes have been unpredictable. Emerging FLASH-RT, delivering dose at ultra-high dose rates, promises to reduce healthy tissue damage while maintaining tumor control. However, the mechanism of this protective effect is not well understood. To bridge these knowledge gaps and promote the clinical adoption of new radiation therapies, the development of quantitative imaging techniques is essential, which are indispensable for conducting rigorous pre-clinical studies. Fluorescence imaging(FI) is a powerful tool for detailed exploration of tumor biology and its response to therapies. Multiplex FI enables the tracking of multiple biological processes, including the migration of tumor and immune cells as well as changes in tissue oxygenation, which are crucial for RT. However, quantifying in vivo fluorescence based on intensity presents challenges. Issues such as tissue autofluorescence, leakage of excitation light into the detection window due to a small Stokes shift of fluorescence, and spectrally dependent tissue absorption could introduce errors in fluorescence quantification. These errors are exacerbated when multiplexing techniques are used, as crosstalk between the emission spectra of fluorophores can further compound inaccuracies. Building on the promising results achieved during the Phase I period and address the aforementioned challenges, we propose significantly enhancing the quantitative capabilities of our fluorescence imaging-guided system through the adoption of fluorescence lifetime(FLiT) imaging. Unlike the intensity-based FI, FLiT is unaffected from autofluorescence, light leakage, absorption and crosstalk among fluorophores. FLiT imaging offers robust quantitative data by measuring the lifetime of fluorescence signal. It thus allows a more accurate distinction between reporters and offers higher accuracy in quantifying fluorophore concentration compared to the intensity-based FI. FLiT imaging is highly complementary to the bioluminescence and fluorescence tomography(BLT/FT) system developed in the Phase I period for guiding radiation delivery and assessing treatment response. A multimodality CBCT/BLT/FLiT/FT imaging capabilities that complements the small animal radiation research platform(SARRP) would provide a powerful platform for pre-clinical radiation research. The development of FLiT imaging to support image-guided radiation studies falls perfectly within the scope of the parent grant and represents a logical extension of the original aims. Extending from the aims of Phase I proposal, the aim for the Phase II research period is to construct a FLiT imaging system compatible with the optical system(MuriGlo) to advance the quantitative imaging and FT-guided capabilities for the SARRP. The success of the extension will lead to a high-specificity and quantitative in vivo fluorescence imaging system. It would advance the already promising BLT/FT-guided system(MuriGlo), effectively tracking multiple biological processes in vivo and their response to therapies.