Abstract
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.
Highlights
In diagnostic mammography breast microcalcifications are the primary evidence in the detection and assessment of early stage breast cancer and impalpable tumor lesions[1,2]
Diagnostic potential and validity of current microcalcification analyses is limited by the fact that morphological descriptors are restricted to the global appearance of microcalcification clusters, since their microstructure remains unresolved with clinical mammography systems[13]
In summary we have presented a novel and non-invasive method using X-ray dark-field mammography for breast microcalcification assessment that overcomes the major shortcomings of current microcalcification evaluation with conventional mammography: first, microscopic resolution is provided through comparison of the global absorption to scattering power of microcalcification clusters, it is unrestricted by the resolution limit of the detector and clinically compatible
Summary
In diagnostic mammography breast microcalcifications are the primary evidence in the detection and assessment of early stage breast cancer (carcinoma in-situ) and impalpable tumor lesions[1,2]. Previous ex-vivo case studies showed an improved diagnostic discriminability between malignant and benign microcalcifications by assessment of their 3D-micromorphology for certain indications, the underlying imaging techniques are unsuitable for clinical, in-vivo mammography: sufficient resolution of the micromorphology requires detector pixel sizes of an order of magnitude smaller than commonly used in clinical mammography. The key factor of the presented method is the simultaneous measurement of absorption (relative decrease in transmission T) and dark-field signal (relative decrease in fringe-visibility V) with a grating-based phase-stepping approach These two contrasts allow the determination and comparison of material specific absorption power μ and scattering power ε of the investigated specimen[21,22,23,24,25]. S. et al utilized this correlation to reveal changes within the microstructure of emphysematous mouse lungs, namely the decay of lung alveoli with disease progression accompanied by a strong decrease in provided scattering power ε, and could successfully discriminate these from healthy lungs[27]
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