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Updated: May 30, 2025

Tumor Hypoxia Assessment: In Vivo 3D Oxygen Imaging Through Electron Paramagnetic Resonance
Published on: February 14, 2025
MR imaging of proton beam-induced oxygen depletion
Juliane Schieferecke1,2, Aswin Hoffmann1,2,3, Jörg Pawelke1,2
1OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
Background:
Previous studies have shown that in-beam magnetic resonance imaging (MRI) can be used to visualize a proton beam during the irradiation of liquid-filled phantoms. The beam energy- and current-dependent local image contrast observed in water was identified to be predominantly caused by beam-induced buoyant convection and associated flow effects. Besides this flow dependency, the MR signal change was found to be characterized by a change in the relaxation time of water, hinting at a radiochemical contribution, which was hypothesized to lie in oxygen depletion-evoked relaxation time lengthening. The elucidation of the underlying contrast mechanism is required to enable the further assessment of the application potential of MRI-based proton beam visualization in tissue.
Purpose:
The underlying radiochemical cause of the observed local beam-induced change in the relaxation time of water should be identified in beam visualization experiments testing the hypothesis of beam-induced oxygen depletion-evoked relaxation time lengthening.
Methods:
Combined irradiation and imaging experiments were performed using static proton pencil beam irradiation, background-nulled inversion recovery (IR) MRI and a range of flow-restricted phantoms differing in initial oxygen concentration and homogeneity. The similarity of the irradiation-induced MRI contrast to the proton pencil beam dose distribution acquired on radiochromic film, the expected dose dependence and temporal stability, the TR dependence as well as the dependence on the initial oxygen concentration and the oxygen consumption rate were tested. Moreover, the feasibility of oxygen depletion-based beam visualization in tissue-mimicking phantoms was assessed. The levels of irradiation-induced oxygen depletion and relaxation time lengthening were estimated based on the measured temperatures and initial oxygen concentrations of the phantoms, the experimentally determined inversion times required for phantom background signal nulling and dosimetric measurements.
Results:
The proton irradiation-induced contrast in background-nulled IR images of well oxygenated phantoms was found similar to the proton pencil beam dose distribution and showed the characteristics expected for oxygen depletion-induced MRI contrast. No beam-induced contrast was observed in the poorly oxygenated, inhomogeneous tissue-mimicking phantoms.
Conclusions:
Proton beam-induced radiochemical oxygen depletion can be visualized using relaxation time contrast-based IR MRI and represents the first identified flow-independent contrast mechanism in MRI-based proton beam visualization in real-time. Beam detection in tissue, however, will be complicated by the increased relaxation time inhomogeneity and the lowered levels of initial oxygen concentration compared to in liquids at atmospheric equilibrium and requires further assessment.
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