Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, D-22607 Hamburg, Germany. Federal University of Technology - Paraná, Av. Sete de Setembro 3165, 80230-901 Curitiba, Brazil.
Biomed Phys Eng Express. 2020 Mar 25;6(3):035012. doi: 10.1088/2057-1976/ab7cad.
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.
SAXS-CT 是一种新兴的强大成像技术，它弥补了从高分辨率局部技术获取的信息和低分辨率、大视场成像获取的信息之间的差距，用于确定有序组织的纳米结构特征，例如骨骼中的矿化胶原。然而，在软组织的情况下，由于纳米结构组织不良和对辐射诱导损伤的高度敏感性等特点，限制了 SAXS-CT 的使用。在这里，我们通过将标本进行冷冻干燥，然后进行福尔马林固定，结合纳米结构调查，在不需要对样本进行染色的情况下，对乳腺癌标本中甘油三酯和胶原纤维的层次排列的三维变化进行了识别和监测。在乳腺癌的侵袭前沿处精确观察到高密度排列的胶原，显示了癌症扩散的方向，而在健康组织所在的部位，则检测到大量的甘油三酯。最后，这里开发的方法提供了一种高分辨率大视场纳米结构探测的途径，通过对正常、良性和恶性人乳腺组织中特征性纳米结构排列的可视化和胶原纤维含量及组织程度的定量，证明了这一点。
