Oxygen tomography by Čerenkov-excited phosphorescence during external beam irradiation

Abstract

The efficacy of radiation therapy depends strongly on tumor oxygenation during irradiation. However, current techniques to measure this parameter in vivo do not facilitate routine monitoring in patients. Herein, we demonstrate a noninvasive method for tomographic imaging of oxygen partial pressure (pO(2)) in deep tissue using the phosphorescence decay of an oxygen-sensitive probe excited by Čerenkov radiation induced by external beam radiotherapy. Tissue-simulating scattering phantoms (60 mm diameter with a 20 mm anomaly) containing platinum(II)-G4 (PtG4), a dendritic porphyrin-based phosphor, whose phosphorescence is quenched in the presence of oxygen, were irradiated with a clinical linear accelerator. The emitted phosphorescence was measured at various positions on the phantom boundary using a spectrograph coupled to an intensified charge-coupled device (ICCD). At each position, PtG4 phosphorescence decay curves were measured by synchronizing the ICCD to the linear accelerator pulses. Tomographic images of phosphorescence yield and lifetime were recovered for phantoms with homogenous PtG4 concentrations and heterogeneous pO(2). Since PtG4 lifetime is strongly and predictably dependent on pO(2) through the Stern-Volmer relationship, tomographic images of pO(2) were also reported, and showed excellent agreement with independent oxygenation measurements. Translating this approach to the clinic could facilitate direct sensing of pO(2) during radiotherapy.

Fig. 1

(a) Diagram of the measurement system consisting of a linear accelerator, radiation/optical tissue phantom, and an optical fiber that couples light from the phantom to a spectrometer with a gated ICCD synchronized to the radiation bursts of the LINAC. (b) Top view of the phantom geometry. (c) A two-dimensional cross-section of the Čerenkov field modeled using Geant4-based architecture for machine-oriented simulations (GAMOS) and used as the excitation field for phosphorescence yield image reconstruction.

Fig. 2

Images of phosphorescence yield from CREL tomography and associated contrast-to-background values for four PtG4 phantom configurations.

Fig. 3

(a) Phosphorescence decays calculated as the average values in the aerated anomaly and anoxic background. (b) Recovered lifetime distribution. (c) ${\mathrm{pO}}_2$ distribution converted from the lifetime distribution using the Stern-Volmer model.