Automated in vivo assessment of vascular response to radiation using a hybrid theranostic X-Ray irradiator/fluorescence molecular imaging system

Farouk Nouizi, Jamison Brooks, Darren M. Zuro, Srideshikan Sargur Madabushi, Dayson Moreira, Marcin Kortylewski, Jerry Froelich, Lydia M. Su, Gultekin Gulsen, Susanta K. Hui

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number9094181
Pages (from-to)93663-93670
Number of pages8
JournalIEEE Access
Volume8
DOIs
StatePublished - Jan 1 2020

Keywords

  • Fluorescence molecular imaging
  • pharmacokinetics
  • preclinical imaging
  • principal component analysis
  • radiation therapy
  • stereotactic body radiotherapy treatments
  • theranostics
  • tumor vascular response

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