Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment

Eno Hysi; Muhannad N. Fadhel; Yanjie Wang; Joseph A. Sebastian; Anoja Giles; Gregory J. Czarnota; Agata A. Exner; Michael C. Kolios

doi:10.1016/j.pacs.2020.100201

Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment

Eno Hysi, Muhannad N. Fadhel, Yanjie Wang, Joseph A. Sebastian, Anoja Giles, Gregory J. Czarnota, Agata A. Exner, Michael C. Kolios^*

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. In vivo experiments were conducted on mice bearing prostate cancer tumors. Combined nanobubble plus radiation treatments were compared against conventional microbubbles and radiation alone (single 8 Gy fraction). Acoustic resolution photoacoustic imaging was used to monitor the effects of the treatments 2- and 24-hs post-administration. Histological examination provided metrics of tumor vascularity and tumoral cell death, both of which were compared to photoacoustic-derived biomarkers. Photoacoustic metrics of oxygen saturation reveal a 20 % decrease in oxygenation within 24 h post-treatment. The spectral slope metric could separate the response of the nanobubble treatments from the microbubble counterparts. This study shows that histopathological assessment correlated well with photoacoustic biomarkers of treatment response.

Original language	English (US)
Article number	100201
Journal	Photoacoustics
Volume	20
DOIs	https://doi.org/10.1016/j.pacs.2020.100201
State	Published - Dec 2020

Funding

This research was undertaken, in part, through grants provided by the Terry Fox Foundation through a Program Project Grant funded through the Hecht Foundation (GJC and MCK), National Institutes of Health (AAE and MCK) and the Natural Sciences and Engineering Research Council of Canada (MCK). EH held a Vanier Canada Graduate Scholarship during the conduct of this research. MF was supported through an NSERC Alexander Graham Bell Graduate Scholarship . The authors would like to acknowledge the assistance of Dr. Azza Al-Mahrouki, Dr. Lauren Wirtzfeld and Nikki Law. The Keenan Research Centre Core Facilities at St. Michael’s Hospital and Dr. Caterina Di Ciano-Oliveira are acknowledged for assistance with histological analysis. The technical support provided by the Toronto office of Fujifilm-VisualSonics is also gratefully recognized. This research was undertaken, in part, through grants provided by the Terry Fox Foundation through a Program Project Grant funded through the Hecht Foundation (GJC and MCK), National Institutes of Health (AAE and MCK) and the Natural Sciences and Engineering Research Council of Canada (MCK). EH held a Vanier Canada Graduate Scholarship during the conduct of this research. MF was supported through an NSERC Alexander Graham Bell Graduate Scholarship. The authors would like to acknowledge the assistance of Dr. Azza Al-Mahrouki, Dr. Lauren Wirtzfeld and Nikki Law. The Keenan Research Centre Core Facilities at St. Michael's Hospital and Dr. Caterina Di Ciano-Oliveira are acknowledged for assistance with histological analysis. The technical support provided by the Toronto office of Fujifilm-VisualSonics is also gratefully recognized.

Keywords

Microbubbles
Nanobubbles
Photoacoustic imaging
Radiation therapy
Vascular disruption

ASJC Scopus subject areas

Atomic and Molecular Physics, and Optics
Radiology Nuclear Medicine and imaging

UN SDGs

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

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10.1016/j.pacs.2020.100201

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title = "Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment",

abstract = "The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. In vivo experiments were conducted on mice bearing prostate cancer tumors. Combined nanobubble plus radiation treatments were compared against conventional microbubbles and radiation alone (single 8 Gy fraction). Acoustic resolution photoacoustic imaging was used to monitor the effects of the treatments 2- and 24-hs post-administration. Histological examination provided metrics of tumor vascularity and tumoral cell death, both of which were compared to photoacoustic-derived biomarkers. Photoacoustic metrics of oxygen saturation reveal a 20 \% decrease in oxygenation within 24 h post-treatment. The spectral slope metric could separate the response of the nanobubble treatments from the microbubble counterparts. This study shows that histopathological assessment correlated well with photoacoustic biomarkers of treatment response.",

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author = "Eno Hysi and Fadhel, \{Muhannad N.\} and Yanjie Wang and Sebastian, \{Joseph A.\} and Anoja Giles and Czarnota, \{Gregory J.\} and Exner, \{Agata A.\} and Kolios, \{Michael C.\}",

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year = "2020",

month = dec,

doi = "10.1016/j.pacs.2020.100201",

language = "English (US)",

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AU - Fadhel, Muhannad N.

AU - Wang, Yanjie

AU - Sebastian, Joseph A.

AU - Giles, Anoja

AU - Czarnota, Gregory J.

AU - Exner, Agata A.

AU - Kolios, Michael C.

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N2 - The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. In vivo experiments were conducted on mice bearing prostate cancer tumors. Combined nanobubble plus radiation treatments were compared against conventional microbubbles and radiation alone (single 8 Gy fraction). Acoustic resolution photoacoustic imaging was used to monitor the effects of the treatments 2- and 24-hs post-administration. Histological examination provided metrics of tumor vascularity and tumoral cell death, both of which were compared to photoacoustic-derived biomarkers. Photoacoustic metrics of oxygen saturation reveal a 20 % decrease in oxygenation within 24 h post-treatment. The spectral slope metric could separate the response of the nanobubble treatments from the microbubble counterparts. This study shows that histopathological assessment correlated well with photoacoustic biomarkers of treatment response.

AB - The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. In vivo experiments were conducted on mice bearing prostate cancer tumors. Combined nanobubble plus radiation treatments were compared against conventional microbubbles and radiation alone (single 8 Gy fraction). Acoustic resolution photoacoustic imaging was used to monitor the effects of the treatments 2- and 24-hs post-administration. Histological examination provided metrics of tumor vascularity and tumoral cell death, both of which were compared to photoacoustic-derived biomarkers. Photoacoustic metrics of oxygen saturation reveal a 20 % decrease in oxygenation within 24 h post-treatment. The spectral slope metric could separate the response of the nanobubble treatments from the microbubble counterparts. This study shows that histopathological assessment correlated well with photoacoustic biomarkers of treatment response.

KW - Microbubbles

KW - Nanobubbles

KW - Photoacoustic imaging

KW - Radiation therapy

KW - Vascular disruption

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Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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