In-vivo X-ray Dark-Field Chest Radiography of a Pig.

X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 × 35 cm2) of a living pig, acquired with clinically compatible parameters (40 s scan time, approx. 80 µSv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking.

X-ray Dark-field Radiography - In-Vivo Diagnosis of Lung Cancer in Mice.

Accounting for about 1.5 million deaths annually, lung cancer is the prevailing cause of cancer deaths worldwide, mostly associated with long-term smoking effects. Numerous small-animal studies are performed currently in order to better understand the pathogenesis of the disease and to develop treatment strategies. Within this letter, we propose to exploit X-ray dark-field imaging as a novel diagnostic tool for the detection of lung cancer on projection radiographs. Here, we demonstrate in living mice bearing lung tumors, that X-ray dark-field radiography provides significantly improved lung tumor detection rates without increasing the number of false-positives, especially in the case of small and superimposed nodules, when compared to conventional absorption-based imaging. While this method still needs to be adapted to larger mammals and finally humans, the technique presented here can already serve as a valuable tool in evaluating novel lung cancer therapies, tested in mice and other small animal models.

Fourier domain image fusion for differential X-ray phase-contrast breast imaging.

X-Ray Phase-Contrast (XPC) imaging is a novel technology with a great potential for applications in clinical practice, with breast imaging being of special interest. This work introduces an intuitive methodology to combine and visualize relevant diagnostic features, present in the X-ray attenuation, phase shift and scattering information retrieved in XPC imaging, using a Fourier domain fusion algorithm. The method allows to present complementary information from the three acquired signals in one single image, minimizing the noise component and maintaining visual similarity to a conventional X-ray image, but with noticeable enhancement in diagnostic features, details and resolution. Radiologists experienced in mammography applied the image fusion method to XPC measurements of mastectomy samples and evaluated the feature content of each input and the fused image. This assessment validated that the combination of all the relevant diagnostic features, contained in the XPC images, was present in the fused image as well.

Advanced Non-Destructive Ocular Visualization Methods by Improved X-Ray Imaging Techniques.

Due to limited X-ray contrast, the use of micro-CT in histology is so far not as widespread as predicted. While specific staining procedures-mostly using iodine-address this shortcoming, long diffusion times restrict its use in the often time-constrained daily routine. Recently, a novel staining protocol has been proposed using a biochemical preconditioning step, which increases the permeability of the cells for the staining agent. This could enable the imaging of entire organs of small mammals at a yet unmatched image quality with reasonable preparation and scan times. We here propose an adaptation of this technique for virtual ophthalmology and histology by volumetrically assessing both human and porcine eyes. Hereby, we demonstrate that (contrast-enhanced) micro-CT can outperform conventional histology in the assessment of tumor entities, as well as functioning as a supplementary tool for surgeons in the positioning of intraocular implants in-vitro and as a general assessment tool for ophthalmologic specimens.

Improved Diagnostics by Assessing the Micromorphology of Breast Calcifications via X-Ray Dark-Field Radiography.

Breast microcalcifications play an essential role in the detection and evaluation of early breast cancer in clinical diagnostics. However, in digital mammography, microcalcifications are merely graded with respect to their global appearance within the mammogram, while their interior microstructure remains spatially unresolved and therefore not considered in cancer risk stratification. In this article, we exploit the sub-pixel resolution sensitivity of X-ray dark-field contrast for clinical microcalcification assessment. We demonstrate that the micromorphology, rather than chemical composition of microcalcification clusters (as hypothesised by recent literature), determines their absorption and small-angle scattering characteristics. We show that a quantitative classification of the inherent microstructure as ultra-fine, fine, pleomorphic and coarse textured is possible. Insights underlying the micromorphological nature of breast calcifications are verified by comprehensive high-resolution micro-CT measurements. We test the determined microtexture of microcalcifications as an indicator for malignancy and demonstrate its potential to improve breast cancer diagnosis, by providing a non-invasive tool for sub-resolution microcalcification assessment. Our results indicate that dark-field imaging of microcalcifications may enhance the diagnostic validity of current microcalcification analysis and reduce the number of invasive procedures.

Low-dose, phase-contrast mammography with high signal-to-noise ratio.

Differential phase-contrast X-ray imaging using a Talbot-Lau interferometer has recently shown promising results for applications in medical imaging. However, reducing the applied radiation dose remains a major challenge. In this study, we consider the realization of a Talbot-Lau interferometer in a high Talbot order to increase the signal-to-noise ratio for low-dose applications. The quantitative performance of π and π/2 systems at high Talbot orders is analyzed through simulations, and the design energy and X-ray spectrum are optimized for mammography. It is found that operation even at very high Talbot orders is feasible and beneficial for image quality. As long as the X-ray spectrum is matched to the visibility spectrum, the SNR continuously increases with the Talbot order for π-systems. We find that the optimal X-ray spectra and design energies are almost independent of the Talbot order and that the overall imaging performance is robust against small variations in these parameters. Discontinuous spectra, such as that from molybdenum, are less robust because the characteristic lines may coincide with minima in the visibility spectra; however, they may offer slightly better performance. We verify this hypothesis by realizing a prototype system with a mean fringe visibility of above 40% at the seventh Talbot order. With this prototype, a proof-of-principle measurement of a freshly dissected breast at reasonable compression to 4 cm is conducted with a mean glandular dose of only 3 mGy but with a high SNR.

Toward Clinically Compatible Phase-Contrast Mammography.

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom.

Improved visualization of breast cancer features in multifocal carcinoma using phase-contrast and dark-field mammography: an ex vivo study.

OBJECTIVES: Conventional X-ray attenuation-based contrast is inherently low for the soft-tissue components of the female breast. To overcome this limitation, we investigate the diagnostic merits arising from dark-field mammography by means of certain tumour structures enclosed within freshly dissected mastectomy samples. METHODS: We performed grating-based absorption, absolute phase and dark-field mammography of three freshly dissected mastectomy samples containing bi- and multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer. Preoperative in vivo imaging (digital mammography, ultrasound, MRI), postoperative histopathological analysis and ex vivo digital mammograms of all samples were acquired for the diagnostic verification of our results. RESULTS: In the diagnosis of multifocal tumour growth, dark-field mammography seems superior to standard breast imaging modalities, providing a better resolution of small, calcified tumour nodules, demarcation of tumour boundaries with desmoplastic stromal response and spiculated soft-tissue strands extending from an invasive ductal breast cancer. CONCLUSIONS: On the basis of selected cases, we demonstrate that dark-field mammography is capable of outperforming conventional mammographic imaging of tumour features in both calcified and non-calcified tumours. Presuming dose optimization, our results encourage further studies on larger patient cohorts to identify those patients that will benefit the most from this promising additional imaging modality. KEY POINTS: • X-ray dark-field mammography provides significantly improved visualization of tumour features • X-ray dark-field mammography is capable of outperforming conventional mammographic imaging • X-ray dark-field mammography provides imaging sensitivity towards highly dispersed calcium grains.

Bi-directional x-ray phase-contrast mammography.

Phase-contrast x-ray imaging is a promising improvement of conventional absorption-based mammography for early tumor detection. This potential has been demonstrated recently, utilizing structured gratings to obtain differential phase and dark-field scattering images. However, the inherently anisotropic imaging sensitivity of the proposed mono-directional approach yields only insufficient diagnostic information, and has low diagnostic sensitivity to highly oriented structures. To overcome these limitations, we present a two-directional x-ray phase-contrast mammography approach and demonstrate its advantages by applying it to a freshly dissected, cancerous mastectomy breast specimen. We illustrate that the two-directional scanning procedure overcomes the insufficient diagnostic value of a single scan, and reliably detects tumor structures, independently from their orientation within the breast. Our results indicate the indispensable diagnostic necessity and benefit of a multi-directional approach for x-ray phase-contrast mammography.