Abstract
SAXS-CT is an emerging powerful imaging technique which bridges the gap between information retrieved from high-resolution local techniques and information from low-resolution, large field-of-view imaging, to determine the nanostructure characteristics of well-ordered tissues, e.g., mineralized collagen in bone. However, in the case of soft tissues, features such as poor nanostructural organization and high susceptibility to radiation-induced damage limit the use of SAXS-CT. Here, by combining the freeze-drying the specimen, preceded by formalin fixation, with the nanostructure survey we identified and monitored alterations on the hierarchical arrangement of triglycerides and collagen fibrils three-dimensionally in breast tumor specimens without requiring sample staining. A high density of aligned collagen was observed precisely on the invasion front of the breast carcinoma, showing the direction of cancer spread, whereas substantial content of triglycerides was identified, where the healthy tissue was located. Finally, the approach developed here provides a path to high-resolution nanostructural probing with a large field-of-view, which was demonstrated through the visualization of characteristic nanostructural arrangement and quantification of content and degree of organization of collagen fibrils in normal, benign and malignant human breast tissue.
Highlights
The development of new technologies reaching nano dimensions promises a significant impact on human health issues
The approach developed here provides a path to highresolution nanostructural probing with a large field-of-view, which was demonstrated through the visualization of characteristic nanostructural arrangement and quantification of content and degree of organization of collagen fibrils in normal, benign and malignant human breast tissue
Based on the remarkable characteristics of each type of breast tissue in the scattering profiles showed in figure 3, the distribution of the collagen fibrils (q = 0.94 nm−1) and the triglycerides (q = 1.46 nm−1) in a single tomography slice through the sample assembly was reconstructed and is presented in figures 4(b) and (c), respectively
Summary
The development of new technologies reaching nano dimensions promises a significant impact on human health issues. The expected breakthroughs are human organ restoration using engineered tissue (Isenberg and Wong 2006), ‘designer’ drugs created from directed assembly of atoms and molecules (Huang et al 2014) as well as an urgent need for personalized targeted treatments for diseases like cancer (Jackson and Chester 2015, National Research Council US Committee on a Framework for Developing a New Taxonomy of Disease 2011, since personalized treatment directed to molecular targets should improve outcome for patients with poor prognosis (Chantrill et al 2015). The availability of brighter x-ray sources, fast and essentially noise-free detectors and automated analysis schemes, enable a new favorable context for the development of high-resolution tomography-based techniques (Bleuet et al 2008, Antoniassi et al 2014, Manohar et al 2016, Romanov et al 2017)
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