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

doi:10.1109/ACCESS.2020.2994943

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

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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 language	English (US)
Article number	9094181
Pages (from-to)	93663-93670
Number of pages	8
Journal	IEEE Access
Volume	8
DOIs	https://doi.org/10.1109/ACCESS.2020.2994943
State	Published - 2020

Bibliographical note

Funding 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.

Publisher Copyright:
© 2013 IEEE.

Keywords

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1109/ACCESS.2020.2994943

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Nouizi, F., Brooks, J., Zuro, D. M., Madabushi, S. S., Moreira, D., Kortylewski, M., Froelich, J., Su, L. M., Gulsen, G., & Hui, S. K. (2020). Automated in vivo assessment of vascular response to radiation using a hybrid theranostic X-Ray irradiator/fluorescence molecular imaging system. IEEE Access, 8, 93663-93670. Article 9094181. https://doi.org/10.1109/ACCESS.2020.2994943

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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.",

keywords = "Fluorescence molecular imaging, pharmacokinetics, preclinical imaging, principal component analysis, radiation therapy, stereotactic body radiotherapy treatments, theranostics, tumor vascular response",

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

note = "Funding 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. Publisher Copyright: {\textcopyright} 2013 IEEE.",

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AU - Madabushi, Srideshikan Sargur

AU - Moreira, Dayson

AU - Kortylewski, Marcin

AU - Froelich, Jerry

AU - Su, Lydia M.

AU - Gulsen, Gultekin

AU - Hui, Susanta K.

N1 - Funding 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. Publisher Copyright: © 2013 IEEE.

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N2 - 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.

AB - 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.

KW - Fluorescence molecular imaging

KW - pharmacokinetics

KW - preclinical imaging

KW - principal component analysis

KW - radiation therapy

KW - stereotactic body radiotherapy treatments

KW - theranostics

KW - tumor vascular response

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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