Functional lung imaging with synchrotron radiation: Methods and preclinical applications.

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.

Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography.

The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented.

Visualisation of calcifications and thin collagen strands in human breast tumour specimens by the diffraction-enhanced imaging technique: a comparison with conventional mammography and histology.

Six excised human breast tissue specimens carrying benign and malignant tumours were examined with the diffraction-enhanced imaging technique. Diffraction-enhanced images were compared with diagnostic screen-film mammograms and the correlation with histological information of the specimens was established. The enhanced visibility of calcifications, some of which were smaller than 0.15 mm in diameter, is reported in detail. Fine details of the structures such as strands of collagen and contours between glandular and adipose tissue, which are barely visible at the contrast detection limit in the conventional absorption-based mammograms, are clearly visible in the diffraction-enhanced images. Microscopic study of the stained histopathological sections unequivocally confirms the correlation of the radiographic findings with the morphologic changes in specimens. An increased soft tissue contrast and a combination of information obtained with disparate diffraction-enhanced images provide better visibility of mammographically indistinguishable features. This kind of additional structural information of the breast tissue is required to improve assessment accuracy and earlier detection of the breast lesions. These advances in image quality make the method a very promising candidate for mammography.

Comparison of synchrotron radiation angiography with conventional angiography for the diagnosis of in-stent restenosis after percutaneous transluminal coronary angioplasty.

AIMS: Synchrotron radiation angiography (SRA) is a novel tool for minimally invasive coronary artery imaging. The method uses subtraction of two images produced at energies bracketing the iodine K-edge after intravenous infusion of iodinated contrast agent. We investigated the accuracy of SRA for detecting in-stent restenosis (ISR). METHODS AND RESULTS: We recruited 57 men, 4-6 months after successful PTCA. We visualized the right coronary artery (RCA) in 27 patients with 36 stented segments [12 segments with ISR>50% by quantitative coronary angiography (QCA)], and the left anterior descending artery (LAD) in 30 patients with 37 stented segments (10 ISR). SRA and QCA were performed within 2 days of each other. Two experienced observers unaware of QCA data evaluated the SRA results. Image quality was good or excellent in most patients. Global sensitivity was 64%, specificity was 95%, and positive and negative predictive values were approximately 85%. Inter-observer kappa concordance coefficient was 0.86. False negatives involved short eccentric lesions and superimposed segments, most frequently of the LAD. False positives occurred in intermediate stenoses slightly overestimated by SRA. CONCLUSION: In men, this minimally invasive approach, using small radiation doses, detects significant ISR in the RCA, but the LAD poses difficulties because of superimposition with others structures.