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Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography.

Yaroshenko A, Hellbach K, Yildirim AÖ, Conlon TM, Fernandez IE, Bech M, Velroyen A, Meinel FG, Auweter S, Reiser M, Eickelberg O, Pfeiffer F - Sci Rep (2015)

Bottom Line: This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung.The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT.As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

View Article: PubMed Central - PubMed

Affiliation: Lehrstuhl für Biomedizinische Physik, Physik-Department &Institut für Medizintechnik, Technische Universität München, Garching, Germany.

ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

No MeSH data available.


Related in: MedlinePlus

Transmission (blue) and dark-field (red) line profiles for a healthy (A) and fibrotic mouse (B).The position of the analyzed line is shown on the chosen radiographies in Fig. 2, mice 5 and 10.
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f3: Transmission (blue) and dark-field (red) line profiles for a healthy (A) and fibrotic mouse (B).The position of the analyzed line is shown on the chosen radiographies in Fig. 2, mice 5 and 10.

Mentions: It can be easily seen that the mice treated with bleomycin developed pulmonary fibrosis of varying severity. We observe that severe pulmonary fibrosis is clearly visible on the conventional x-ray transmission images, as well as the dark-field radiograms (e.g. mouse 9). In case of severe fibrosis, alveolar airspaces and perialveolar regions are subject to significantly increased extracellular matrix (ECM) and coagulation product deposition (as shown in Fig. 1B). Therefore, severely affected regions of the lung can be identified as regions of decreased x-ray transmission. The dark-field signal of the lung originates from the x-ray refractions on multiple air-tissue interfaces23. Both simulations33 and experimental results2729 have shown that the reduction of the number of interfaces results in decrease of x-ray scattering. Therefore, control lungs appear bright on the dark-field images (Fig. 2B, mice 1–5) and regions of the lung affected by fibrosis yield significantly less scattering and negligible dark-field signal. In cases of mild and moderate fibrosis (e.g. Fig. 2, animals 6 and 8), x-ray transmission images do not provide a clear signal difference between healthy and fibrotic lung tissue. By contrast, alterations in the lung parenchyma are directly and more sensitively visualized on the dark-field radiograms. Thus, changes in the lung parenchyma can be precisely observed for mouse 6 & 8 in the dark-field but not on the transmission images. To further highlight the superiority of x-ray dark field for the detection of fibrotic changes, a line plot through a healthy (Fig. 2 mouse 5) and a fibrotic (mouse 10) animal for both signals is shown in Fig. 3. On this plot both signals are scaled between 0 and 1. It can be observed that the difference in signal between the right healthy lung and fibrotic left lung in Fig. 3B is very prominent in the dark-field but not in the transmission signal. To estimate the improvement in diagnostic value of x-ray dark-field imaging over conventional transmission, the diagnostic power of both imaging modalities was quantified for the control and the fibrotic animals. For the analysis a mask was manually created on the radiograms including all of the lung tissue, excluding the heart shadow and the ribcage. Figure 4A,B show a typical identical mask for a transmission and a dark-field radiogram.


Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography.

Yaroshenko A, Hellbach K, Yildirim AÖ, Conlon TM, Fernandez IE, Bech M, Velroyen A, Meinel FG, Auweter S, Reiser M, Eickelberg O, Pfeiffer F - Sci Rep (2015)

Transmission (blue) and dark-field (red) line profiles for a healthy (A) and fibrotic mouse (B).The position of the analyzed line is shown on the chosen radiographies in Fig. 2, mice 5 and 10.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664921&req=5

f3: Transmission (blue) and dark-field (red) line profiles for a healthy (A) and fibrotic mouse (B).The position of the analyzed line is shown on the chosen radiographies in Fig. 2, mice 5 and 10.
Mentions: It can be easily seen that the mice treated with bleomycin developed pulmonary fibrosis of varying severity. We observe that severe pulmonary fibrosis is clearly visible on the conventional x-ray transmission images, as well as the dark-field radiograms (e.g. mouse 9). In case of severe fibrosis, alveolar airspaces and perialveolar regions are subject to significantly increased extracellular matrix (ECM) and coagulation product deposition (as shown in Fig. 1B). Therefore, severely affected regions of the lung can be identified as regions of decreased x-ray transmission. The dark-field signal of the lung originates from the x-ray refractions on multiple air-tissue interfaces23. Both simulations33 and experimental results2729 have shown that the reduction of the number of interfaces results in decrease of x-ray scattering. Therefore, control lungs appear bright on the dark-field images (Fig. 2B, mice 1–5) and regions of the lung affected by fibrosis yield significantly less scattering and negligible dark-field signal. In cases of mild and moderate fibrosis (e.g. Fig. 2, animals 6 and 8), x-ray transmission images do not provide a clear signal difference between healthy and fibrotic lung tissue. By contrast, alterations in the lung parenchyma are directly and more sensitively visualized on the dark-field radiograms. Thus, changes in the lung parenchyma can be precisely observed for mouse 6 & 8 in the dark-field but not on the transmission images. To further highlight the superiority of x-ray dark field for the detection of fibrotic changes, a line plot through a healthy (Fig. 2 mouse 5) and a fibrotic (mouse 10) animal for both signals is shown in Fig. 3. On this plot both signals are scaled between 0 and 1. It can be observed that the difference in signal between the right healthy lung and fibrotic left lung in Fig. 3B is very prominent in the dark-field but not in the transmission signal. To estimate the improvement in diagnostic value of x-ray dark-field imaging over conventional transmission, the diagnostic power of both imaging modalities was quantified for the control and the fibrotic animals. For the analysis a mask was manually created on the radiograms including all of the lung tissue, excluding the heart shadow and the ribcage. Figure 4A,B show a typical identical mask for a transmission and a dark-field radiogram.

Bottom Line: This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung.The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT.As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

View Article: PubMed Central - PubMed

Affiliation: Lehrstuhl für Biomedizinische Physik, Physik-Department &Institut für Medizintechnik, Technische Universität München, Garching, Germany.

ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

No MeSH data available.


Related in: MedlinePlus