Quantitative imaging of tumor vasculature using multispectral optoacoustic tomography (MSOT)

Michal R. Tomaszewski, Isabel Quiros-Gonzalez, James Joseph, Sarah E. Bohndiek

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The ability to evaluate tumor oxygenation in the clinic could indicate prognosis and enable treatment monitoring, since oxygen deficient cancer cells are often more resistant to chemotherapy and radiotherapy. MultiSpectral Optoacoustic Tomography (MSOT) is a hybrid technique combining the high contrast of optical imaging with spatial resolution and penetration depth similar to ultrasound. We hypothesized that MSOT could reveal both tumor vascular density and function based on modulation of blood oxygenation.

We performed MSOT on nude mice (n=8) bearing subcutaneous xenograft PC3 tumors using an inVision 256 (iThera Medical). The mice were maintained under inhalation anesthesia during imaging and respired oxygen content was modified from 21% to 100% and back. After imaging, Hoechst 33348 was injected to indicate vascular perfusion and permeability. Tumors were then extracted for histopathological analysis and fluorescence microscopy. The acquired data was analyzed to extract a bulk measurement of blood oxygenation (SO2MSOT) from the whole tumor using different approaches. The tumors were also automatically segmented into 5 regions to investigate the effect of depth on SO2MSOT.

Baseline SO2MSOT values at 21% and 100% oxygen breathing showed no relationship with ex vivo measures of vascular density or function, while the change in SO2MSOT showed a strong negative correlation to Hoechst intensity (r=- 0.92, p=0.0016). Tumor voxels responding to oxygen challenge were spatially heterogeneous. We observed a significant drop in SO2 MSOT value with tumor depth following a switch of respiratory gas from air to oxygen (0.323±0.017 vs. 0.11±0.05, p=0.009 between 0 and 1.5mm depth), but no such effect for air breathing (0.265±0.013 vs. 0.19±0.04, p=0.14 between 0 and 1.5mm depth).

Our results indicate that in subcutaneous prostate tumors, baseline SO2MSOT levels do not correlate to tumor vascular density or function while the magnitude of the response to oxygen challenge provides insight into these parameters. Future work will include validation using in vivo imaging and protocol optimization for clinical application.

Original languageEnglish
Title of host publicationPhotons Plus Ultrasound
Subtitle of host publicationImaging and Sensing 2017
EditorsAlexander A. Oraevsky, Lihong V. Wang
PublisherSociety of Photo-optical Instrumentation Engineers
Number of pages9
ISBN (Electronic)9781510605695
DOIs
Publication statusPublished - 3 Mar 2017
EventPhotons Plus Ultrasound: Imaging and Sensing 2017 - San Francisco, United States
Duration: 29 Jan 20171 Feb 2017

Publication series

NameProceedings of SPIE
Volume10064
ISSN (Print)1605-7422

Conference

ConferencePhotons Plus Ultrasound: Imaging and Sensing 2017
CountryUnited States
CitySan Francisco
Period29/01/171/02/17

Keywords

  • Hemodynamics
  • MSOT
  • Optoacoustic
  • Oxygenation
  • Photoacoustic
  • Tumor
  • Vasculature

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  • Cite this

    Tomaszewski, M. R., Quiros-Gonzalez, I., Joseph, J., & Bohndiek, S. E. (2017). Quantitative imaging of tumor vasculature using multispectral optoacoustic tomography (MSOT). In A. A. Oraevsky, & L. V. Wang (Eds.), Photons Plus Ultrasound: Imaging and Sensing 2017 [100640N] (Proceedings of SPIE; Vol. 10064). Society of Photo-optical Instrumentation Engineers. https://doi.org/10.1117/12.2251865