Detection and Early Phase Assessment of Radiation-Induced Lung Injury in Mice Using Micro-CT

Abstract

Radiation therapy is an important therapeutic modality for thoracic malignancies. However, radiation-induced pulmonary injuries such as radiation pneumonitis and fibrosis are major dose-limiting factors. Previous research shows that micro-computed tomography (micro-CT) can detect radiation-induced lung injuries a few months following irradiation, but studies to assess the early response of lung tissue are lacking. The aim of this study was to determine if micro-CT could be used to detect and assess early-phase radiation–induced lung injury in mice. Twenty-one animals were divided into three groups: normal (n = 7), one day after x-ray exposure (n = 7), and at four days after x-ray exposure (n = 7). The x-ray-exposed groups received a single dose of 20 Gy, to the whole lung. Histology showed enlargements of the air space (Lm: mean chord length) following irradiation. 40.5±3.8 µm and 60.0±6.9 µm were observed after one and four days, respectively, compared to 26.5±3.1 µm in normal mice. Three-dimensional micro-CT images were constructed and histograms of radiodensity - Hounsfield Units (HU) - were used to assess changes in mouse lungs. Radiation-induced lung injury was observed in irradiated mice, by the use of two parameters which were defined as shifts in peak HU between −200 to −800 HU (PeakHU) and increase in the number of pixels at −1000 HU (Number-1000). These parameters were correlated with histological changes. The results demonstrate that micro-CT can be used for the early detection and assessment of structural and histopathological changes resulting from radiation-induced lung injury in mice. Micro-CT has the advantage, over traditional histological techniques, of allowing longitudinal studies of lung disease progression and assessment of the entire lung, while reducing the number of animals required for such studies.

Radiation-induced CT number changes in GTV and parotid glands during the course of radiation therapy for nasopharyngeal cancer

“…3,5,[11][12][13] It has been reported that radiation can lead to electron density changes in the lung and liver, as observed from CT images. [14][15][16][17][18] The CT number (CTN) changes were found to be associated with radiation injuries.…”

A new CT-based method to quantify radiation-induced lung damage in patients

“…However, also here the relationship to patient complaints and physician assessment remains weak [8,9]. Others rather quantify the net outcome in terms of changes in density [5][6][7]24,25]. Since radiological change is one of the criteria of physician-rated toxicity, density changes are related to it, but this relation is not very strong [24,25].…”

“…This diagnostic uncertainty may be decreased by using objective quantitative parameters by e.g. imaging of underlying biological effects [4], changes in density [5][6][7] or consequential changes in different aspects of pulmonary function [8,9].…”

“…This diagnostic uncertainty may be decreased by using objective quantitative parameters by e.g. imaging of underlying biological effects [4], changes in density [5][6][7] or consequential changes in different aspects of pulmonary function [8,9].Changes observed on CT-scans may reflect radiation-induced changes in lung tissue including parenchymal inflammation and fibrosis [10,11]. Besides direct measurements of biological changes, several studies therefore utilized quantitative analysis of CT-scans as a surrogate for histopathological changes after chest radiotherapy [12][13][14].…”

In Vivo Imaging of Mouse Cochlea by Optical Coherence Tomography

“…Moreover, the use of contrast agents contains the risk of inner ear impairment when administered locally and the possibility of nephrogenic systemic fibrosis when administered systemically (23). Although micro-CT has an axial resolution of about 1 to 100 Km (24), this method is not acceptable for living animals because of the serious tissue damage that results from the high-dose ionizing radiation (25).…”