• Evaluation of acute esophageal radiation-induced damage using magnetic resonance imaging: a feasibility study in mice

      Jelvehgaran, P; Steinberg, JD; Khmelinskii, A; Borst, G; Song, JY; de Wit, N; de Bruin, DM; van Herk, Marcel; Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands (2019)
      BACKGROUND: Thoracic and head and neck cancer radiation therapy (RT) can cause damage to nearby healthy organs such as the esophagus, causing acute radiation-induced esophageal damage (ARIED). A non-invasive method to detect and monitor ARIED can facilitate optimizing RT to avoid ARIED while improving local tumor control. Current clinical guidelines are limited to scoring the esophageal damage based on the symptoms of patients. Magnetic resonance imaging (MRI) is a non-invasive imaging modality that may potentially visualize radiation-induced organ damage. We investigated the feasibility of using T2-weighted MRI to detect and monitor ARIED using a two-phased study in mice. METHODS: The first phase aimed to establish the optimal dose level at which ARIED is inducible and to determine the time points where ARIED is detectable. Twenty four mice received a single dose delivery of 20 and 40?Gy at proximal and distal spots of 10.0?mm (in diameter) on the esophagus. Mice underwent MRI and histopathology analysis with esophageal resection at two, three, and 4 weeks post-irradiation, or earlier in case mice had to be euthanized due to humane endpoints. In the second phase, 32 mice received a 40?Gy single dose and were studied at two, three, and 7 days post-irradiation. We detected ARIED as a change in signal intensity of the MRI images. We measured the width of the hyperintense area around the esophagus in all mice that underwent MRI prior to and after irradiation. We conducted a blind qualitative comparison between MRI findings and histopathology as the gold standard. RESULTS/CONCLUSIONS: A dose of 40?Gy was needed to induce substantial ARIED. MRI detected ARIED as high signal intensity, visible from 2 days post-irradiation. Quantitative MRI analysis showed that the hyperintense area around the esophagus with severe ARIED was 1.41?mm wider than with no damage and MRI-only mice. The overall sensitivity and specificity were 56 and 43% respectively to detect any form of ARIED. However, in this study MRI correctly detected 100% of severe ARIED cases. Our two-phased preclinical study showed that MRI has the potential to detect ARIED as a change in signal intensity and width of enhancement around the esophagus.
    • Optical coherence tomography to detect acute esophageal radiation-induced damage in mice: a validation study

      Jelvehgaran, P; de Bruin, DM; Khmelinskii, A; Borst, G; Steinberg, JD; Song, JY; de Vos, J; van Leeuwen, TG; Alderliesten, T; de Boer, JF; et al. (2019)
      Radiation therapy for patients with non-small-cell lung cancer is hampered by acute radiation-induced toxicity in the esophagus. This study aims to validate that optical coherence tomography (OCT), a minimally invasive imaging technique with high resolution (~10 ?m), is able to visualize and monitor acute radiation-induced esophageal damage (ARIED) in mice. We compare our findings with histopathology as the gold standard. Irradiated mice receive a single dose of 40 Gy at proximal and distal spots of the esophagus of 10.0 mm in diameter. We scan mice using OCT at two, three, and seven days post-irradiation. In OCT analysis we define ARIED as a presence of distorted esophageal layering, change in backscattering signal properties, or change in the esophageal wall thickness. The average esophageal wall thickness is 0.53 mm larger on OCT when ARIED is present based on histopathology. The overall sensitivity and specificity of OCT to detect ARIED compared to histopathology are 94 % and 47 %, respectively. However, the overall sensitivity of OCT to assess ARIED is 100% seven days post-irradiation. We validated the capability of OCT to detect ARIED induced by high doses in mice. Nevertheless, clinical studies are required to assess the potential role of OCT to visualize ARIED in humans. This article is protected by copyright. All rights reserved.