Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography

Ghayathri Balasundaram, Lu Ding, Xiuting Li, Amalina Binte Ebrahim Attia, Xose Luis Dean-Ben, Chris Jun Hui Ho, Prashant Chandrasekharan, Hui Chien Tay, Hann Qian Lim, Chee Bing Ong, Ralph P. Mason, Daniel Razansky, Malini Olivo

Research output: Contribution to journalArticle

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Abstract

PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO2) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO2 upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors. We employed a newly-developed non-negative constrained approach for combined MSOT image reconstruction and unmixing in order to quantitatively map sO2 in whole mouse brains. RESULTS: Upon longitudinal monitoring, tumors could be detected in mouse brains using single-wavelength data as early as 6 days post tumor cell inoculation. Fifteen days post-inoculation, tumors had higher sO2 of 63 ± 11% (n = 5, P <.05) against 48 ± 7% in the corresponding contralateral brain, indicating their hyperoxic status. In a different set of animals, 42 days post-inoculation, tumors had lower sO2 of 42 ± 5% against 49 ± 4% (n = 3, P <.05) in the contralateral side, indicating their hypoxic status. Upon CA4P administration, sO2 in 15 days post-inoculation tumors dropped from 61 ± 9% to 36 ± 1% (n = 4, P <.01) within one hour, then reverted to pre CA4P treatment values (63 ± 6%) and remained constant until the last observation time point of 6 hours. CONCLUSION: With the help of advanced post processing algorithms, MSOT was capable of monitoring the tumor growth and assessing hemodynamic changes upon administration of VDAs in orthotopic GBMs.

Original languageEnglish (US)
Pages (from-to)1251-1258
Number of pages8
JournalTranslational Oncology
Volume11
Issue number5
DOIs
StatePublished - Oct 1 2018

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Glioblastoma
Tomography
Neoplasms
Brain
Therapeutics
Blood Vessels
Computer-Assisted Image Processing
Growth
Nude Mice
Hemodynamics
Observation
Oxygen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography. / Balasundaram, Ghayathri; Ding, Lu; Li, Xiuting; Attia, Amalina Binte Ebrahim; Dean-Ben, Xose Luis; Ho, Chris Jun Hui; Chandrasekharan, Prashant; Tay, Hui Chien; Lim, Hann Qian; Ong, Chee Bing; Mason, Ralph P.; Razansky, Daniel; Olivo, Malini.

In: Translational Oncology, Vol. 11, No. 5, 01.10.2018, p. 1251-1258.

Research output: Contribution to journalArticle

Balasundaram, G, Ding, L, Li, X, Attia, ABE, Dean-Ben, XL, Ho, CJH, Chandrasekharan, P, Tay, HC, Lim, HQ, Ong, CB, Mason, RP, Razansky, D & Olivo, M 2018, 'Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography', Translational Oncology, vol. 11, no. 5, pp. 1251-1258. https://doi.org/10.1016/j.tranon.2018.07.001
Balasundaram, Ghayathri ; Ding, Lu ; Li, Xiuting ; Attia, Amalina Binte Ebrahim ; Dean-Ben, Xose Luis ; Ho, Chris Jun Hui ; Chandrasekharan, Prashant ; Tay, Hui Chien ; Lim, Hann Qian ; Ong, Chee Bing ; Mason, Ralph P. ; Razansky, Daniel ; Olivo, Malini. / Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography. In: Translational Oncology. 2018 ; Vol. 11, No. 5. pp. 1251-1258.
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abstract = "PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO2) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO2 upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors. We employed a newly-developed non-negative constrained approach for combined MSOT image reconstruction and unmixing in order to quantitatively map sO2 in whole mouse brains. RESULTS: Upon longitudinal monitoring, tumors could be detected in mouse brains using single-wavelength data as early as 6 days post tumor cell inoculation. Fifteen days post-inoculation, tumors had higher sO2 of 63 ± 11{\%} (n = 5, P <.05) against 48 ± 7{\%} in the corresponding contralateral brain, indicating their hyperoxic status. In a different set of animals, 42 days post-inoculation, tumors had lower sO2 of 42 ± 5{\%} against 49 ± 4{\%} (n = 3, P <.05) in the contralateral side, indicating their hypoxic status. Upon CA4P administration, sO2 in 15 days post-inoculation tumors dropped from 61 ± 9{\%} to 36 ± 1{\%} (n = 4, P <.01) within one hour, then reverted to pre CA4P treatment values (63 ± 6{\%}) and remained constant until the last observation time point of 6 hours. CONCLUSION: With the help of advanced post processing algorithms, MSOT was capable of monitoring the tumor growth and assessing hemodynamic changes upon administration of VDAs in orthotopic GBMs.",
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T1 - Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography

AU - Balasundaram, Ghayathri

AU - Ding, Lu

AU - Li, Xiuting

AU - Attia, Amalina Binte Ebrahim

AU - Dean-Ben, Xose Luis

AU - Ho, Chris Jun Hui

AU - Chandrasekharan, Prashant

AU - Tay, Hui Chien

AU - Lim, Hann Qian

AU - Ong, Chee Bing

AU - Mason, Ralph P.

AU - Razansky, Daniel

AU - Olivo, Malini

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N2 - PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO2) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO2 upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors. We employed a newly-developed non-negative constrained approach for combined MSOT image reconstruction and unmixing in order to quantitatively map sO2 in whole mouse brains. RESULTS: Upon longitudinal monitoring, tumors could be detected in mouse brains using single-wavelength data as early as 6 days post tumor cell inoculation. Fifteen days post-inoculation, tumors had higher sO2 of 63 ± 11% (n = 5, P <.05) against 48 ± 7% in the corresponding contralateral brain, indicating their hyperoxic status. In a different set of animals, 42 days post-inoculation, tumors had lower sO2 of 42 ± 5% against 49 ± 4% (n = 3, P <.05) in the contralateral side, indicating their hypoxic status. Upon CA4P administration, sO2 in 15 days post-inoculation tumors dropped from 61 ± 9% to 36 ± 1% (n = 4, P <.01) within one hour, then reverted to pre CA4P treatment values (63 ± 6%) and remained constant until the last observation time point of 6 hours. CONCLUSION: With the help of advanced post processing algorithms, MSOT was capable of monitoring the tumor growth and assessing hemodynamic changes upon administration of VDAs in orthotopic GBMs.

AB - PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO2) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO2 upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors. We employed a newly-developed non-negative constrained approach for combined MSOT image reconstruction and unmixing in order to quantitatively map sO2 in whole mouse brains. RESULTS: Upon longitudinal monitoring, tumors could be detected in mouse brains using single-wavelength data as early as 6 days post tumor cell inoculation. Fifteen days post-inoculation, tumors had higher sO2 of 63 ± 11% (n = 5, P <.05) against 48 ± 7% in the corresponding contralateral brain, indicating their hyperoxic status. In a different set of animals, 42 days post-inoculation, tumors had lower sO2 of 42 ± 5% against 49 ± 4% (n = 3, P <.05) in the contralateral side, indicating their hypoxic status. Upon CA4P administration, sO2 in 15 days post-inoculation tumors dropped from 61 ± 9% to 36 ± 1% (n = 4, P <.01) within one hour, then reverted to pre CA4P treatment values (63 ± 6%) and remained constant until the last observation time point of 6 hours. CONCLUSION: With the help of advanced post processing algorithms, MSOT was capable of monitoring the tumor growth and assessing hemodynamic changes upon administration of VDAs in orthotopic GBMs.

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