期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2022
卷号:119
期号:5
DOI:10.1073/pnas.2118876119
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Significance
Understanding cancer’s biomarker, microenvironment, and heterogeneity at the tissue level promises to improve cancer biology and clinical diagnosis and treatment. Many histological imaging techniques have been developed for this purpose. In this study, benefiting from the development of quantum sensing with nitrogen-vacancy (NV) centers in diamond, we proposed and experimentally realized micrometer-resolution magnetic imaging of tumor tissues in an NV-diamond magnetic microscope, magnetically imaging and quantifying cancer biomarkers. Moreover, we achieved the correlated magnetic and optical imaging in the same tissue section. The histological magnetometry exhibits excellent signal stability, negligible magnetic background, and accurate magnetic quantification. Our method thus opens the door to micrometer-resolution magnetic imaging of biological tissues and has the potential to influence research and histopathology of cancer.
Histological imaging is essential for the biomedical research and clinical diagnosis of human cancer. Although optical microscopy provides a standard method, it is a persistent goal to develop new imaging methods for more precise histological examination. Here, we use nitrogen-vacancy centers in diamond as quantum sensors and demonstrate micrometer-resolution immunomagnetic microscopy (IMM) for human tumor tissues. We immunomagnetically labeled cancer biomarkers in tumor tissues with magnetic nanoparticles and imaged them in a 400-nm resolution diamond-based magnetic microscope. There is barely magnetic background in tissues, and the IMM can resist the impact of a light background. The distribution of biomarkers in the high-contrast magnetic images was reconstructed as that of the magnetic moment of magnetic nanoparticles by employing deep-learning algorithms. In the reconstructed magnetic images, the expression intensity of the biomarkers was quantified with the absolute magnetic signal. The IMM has excellent signal stability, and the magnetic signal in our samples had not changed after more than 1.5 y under ambient conditions. Furthermore, we realized multimodal imaging of tumor tissues by combining IMM with hematoxylin-eosin staining, immunohistochemistry, or immunofluorescence microscopy in the same tissue section. Overall, our study provides a different histological method for both molecular mechanism research and accurate diagnosis of human cancer.
关键词:entumor tissuehistological magnetometrynitrogen-vacancy centermicrometer-resolution magnetic imagingabsolute magnetic quantification