Hypofractionated stereotactic body radiotherapy treatments (SBRT) have demonstrated impressive results for the treatment of a variety of solid tumors. The role of tumor supporting vasculature damage in treatment outcome for SBRT has been intensely debated and studied. Fast, non-invasive, longitudinal assessments of tumor vasculature would allow for thorough investigations of vascular changes correlated with SBRT treatment response. In this paper, we present a novel theranostic system which incorporates a fluorescence molecular imager into a commercial, preclinical, microCT-guided, irradiator and was designed to quantify tumor vascular response (TVR) to targeted radiotherapy. This system overcomes the limitations of single-timepoint imaging modalities by longitudinally assessing spatiotemporal differences in intravenously-injected ICG kinetics in tumors before and after high-dose radiation. Changes in ICG kinetics were rapidly quantified by principle component (PC) analysis before and two days after 10 Gy targeted tumor irradiation. A classifier algorithm based on PC data clustering identified pixels with TVR. Results show that two days after treatment, a significant delay in ICG clearance as measured by exponential decay (40.5± 16.1% P = 0.0405 Paired t-test n = 4) was observed. Changes in the mean normalized first and second PC feature pixel values (PC1 PC2) were found (P = 0.0559, 0.0432 paired t-test), suggesting PC based analysis accurately detects changes in ICG kinetics. The PC based classification algorithm yielded spatially-resolved TVR maps. Our first-of-its-kind theranostic system, allowing automated assessment of TVR to SBRT, will be used to better understand the role of tumor perfusion in metastasis and local control.
Bibliographical noteFunding Information:
This work was supported in part by the National Institutes of Health (NIH) under Grant P30CA033572 (Cancer Center-CoH) and Grant P30CA62203 (Cancer Center-UCI). The work of Marcin Kortylewski was supported in part by the National Institutes of Health under Grant R01CA215183 and in part by the Department of Defense under Grant W81XWH1910852. The work of Jerry Froelich was supported by the Merle and Fern Loken Professorship in Medical Physics Award. The work of Gultekin Gulsen supported by the National Institutes of Health under Grant R21 CA191389. The work of Susanta K. Hui was supported in part by the National Institutes of Health under Grant 1R01CA154491, in part by the City of Hope Excellence Award, and in part by the ONCOTEST.
© 2013 IEEE.
- Fluorescence molecular imaging
- preclinical imaging
- principal component analysis
- radiation therapy
- stereotactic body radiotherapy treatments
- tumor vascular response