Dynamic oxygenation measurements.

Poor oxygenation of solid tumors has been linked with resistance to chemo- and radio-therapy and poor patient outcomes. Hence, non-invasive imaging of oxygen supply and demand in tumors could improve disease staging and therapeutic monitoring. MSOT can provide static images of endogenous haemoglobin concentration and oxygenation. In a recent study, a group at Cambridge University demonstrated oxygen enhanced (OE)-OT, exploiting an oxygen gas challenge to visualize the spatiotemporal heterogeneity of tumor vascular function.

More specifically, the study shows that tracking oxygenation dynamics using oxygen enhanced optoacoustic tomography OE-OT reveals significant differences between two prostate cancer models in nude mice with markedly different vascular function (PC3 & LNCaP), which appear identical in static OT.

Temporal evolution of oxygenation signals with OE-OT (A), derived from mice bearing a PC3 s.c. tumor
Spectral changes over time in PC3 (B) and LNCaP (C) cell lines
Mean SO2MSOT in PC3 (D) and LNCAP (E) cell lines

LNCaP tumors showed a spatially heterogeneous response within and between tumors, with a substantial but slow response to the gas challenge, aligned with ex vivo analysis, which revealed a generally perfused and viable tumor with marked areas of haemorrhage. PC3 tumors had a lower fraction of responding pixels compared to LNCaP with a high disparity between rim and core response. While the PC3 core showed little or no dynamic response, the rim showed a rapid change, consistent with ex vivo findings of hypoxic and necrotic core tissue surrounded by a rim of mature and perfused vasculature.

(A), representative images showing the spatial distribution of MSOT-derived OE-OT signals; THb, total hemoglobin; SO2MSOT(Air/O2), O2 saturation before/after challenge; RF, responding fraction of pixels in the tumor
(B), quantification of heterogeneous MSOT signals shown in (A)

OE-OT metrics are shown to be highly repeatable and correlate directly on a per-tumor basis to tumor vessel function assessed ex vivo. OE-OT provides a non-invasive approach to reveal the complex dynamics of tumor vessel perfusion, permeability and vasoactivity in real time. The findings of this study indicate that OE-OT holds potential for application in prostate cancer patients, to improve delineation of aggressive and indolent disease as well as in patient stratification for chemo- and radio-therapy.

Tomaszewski MR et al., Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer, Theranostics 2017; 7(11):2900-2913.

  • Tomaszewski MR et al.,
    Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer,
    Theranostics 2017; 7(11):2900-2913. DOI:10.7150/thno.19841.
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