X-ray dark-field radiography facilitates the diagnosis of pulmonary fibrosis in a mouse model

Abstract

The aim of this study was to evaluate whether diagnosing pulmonary fibrosis with projection radiography can be improved by using X-ray dark-field radiograms. Pulmonary X-ray transmission and dark-field images of C57Bl/6N mice, either treated with bleomycin to induce pulmonary fibrosis or PBS to serve as controls, were acquired with a prototype grating-based small-animal scanner. Two blinded readers, both experienced radiologists and familiar with dark-field imaging, had to assess dark-field and transmission images for the absence or presence of fibrosis. Furthermore readers were asked to grade their stage of diagnostic confidence. Histological evaluation of the lungs served as the standard of reference in this study. Both readers showed a notably higher diagnostic confidence when analyzing the dark-field radiographs (p < 0.001). Diagnostic accuracy improved significantly when evaluating the lungs in dark-field images alone (p = 0.02) or in combination with transmission images (p = 0.01) compared to sole analysis of absorption images. Interreader agreement improved from good when assessing only transmission images to excellent when analyzing dark-field images alone or in combination with transmission images. Adding dark-field images to conventional transmission images in a murine model of pulmonary fibrosis leads to an improved diagnosis of this disease on chest radiographs.

Inhibition of B cell–dependent lymphoid follicle formation prevents lymphocytic bronchiolitis after lung transplantation

“…While no major macroscopic changes were detected in syngeneic grafts (B6→B6), mismatched grafts (HLA→B6) demonstrated color fading and shrinking ( Figure 1A) but no signs of acute parenchymal cellular rejection. Functionally, HLA→B6 grafts showed significantly reduced scatter in x-ray dark-field images 1 and 2 months after transplantation, compared with control syngeneic grafts, indicating pathological tissue remodeling ( Figure 1, B and C) (27,28). In addition, HLA→B6 grafts displayed functional impairment, as evidenced by lung function measurements (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.123971DS1).…”

Translation from murine to human lung imaging using x-ray dark field radiography: A simulation study

“…In recent years x-ray dark field (DF) imaging has evolved into a promising tool for lung imaging [ 1 ] based on its sensitivity to the air-tissue transitions in the alveoli. Increased detectability of emphysema [ 2 – 5 ], fibrosis [ 6 , 7 ] and pneumothoraxes [ 8 , 9 ] has been demonstrated. Dark field images can be obtained using various methods [ 10 – 12 ], but the present study focuses on grating interferometry based techniques (GI) [ 13 ] as most DF lung applications in the literature make use of this implementation.…”

“…The majority of the pulmonary DF imaging feasibility studies performed today, use murine models [ 2 , 4 – 7 , 23 – 26 ]; the translation to human lung imaging is therefore not obvious as the DF response strongly depends on microscopic characteristics of the lung tissue. In humans, the alveoli typically range between 200 and 400 μ m, which is a factor of five larger than in mice (39–80 μ m) [ 27 ], and therefore, following Eq ( 5 ), a drop in the linear diffusion coefficient is expected.…”

Optimization of in vivo murine X-ray dark-field computed tomography

“…An X-ray phase-contrast and dark-field CT scanner for small animals has been developed over the past few years 8,9 . The dark-field signal is highly sensitive to scattering by the alveoli in the lung 10 , therefore first experimental results with this scanner could successfully demonstrated the potential of dark-field radiography for detection and staging of pulmonary diseases such as pulmonary emphysema [11][12][13] , pulmonary fibrosis 14 , and pulmonary carcinoma [15][16][17] . Healthy alveolar lung tissue causes a strong dark-field signal, as multiple scattering between air and the alveolar tissue occurs.…”