Chromatin laser imaging reveals abnormal nuclear changes for early cancer detection

Biomed Opt Express. 2019 Jan 24;10(2):838-854. doi: 10.1364/BOE.10.000838. eCollection 2019 Feb 1.


We developed and applied rapid scanning laser-emission microscopy (LEM) to detect abnormal changes in cell nuclei for early diagnosis of cancer and cancer precursors. Regulation of chromatins is essential for genetic development and normal cell functions, while abnormal nuclear changes may lead to many diseases, in particular, cancer. The capability to detect abnormal changes in "apparently normal" tissues at a stage earlier than tumor development is critical for cancer prevention. Here we report using LEM to analyze colonic tissues from mice at-risk for colon cancer (induced by a high-fat diet) by detecting pre-polyp nuclear abnormality. By imaging the lasing emissions from chromatins, we discovered that, despite the absence of observable lesions, polyps, or tumors under stereoscope, high-fat mice exhibited significantly lower lasing thresholds than low-fat mice. The low lasing threshold is, in fact, very similar to that of adenomas and is caused by abnormal cell proliferation and chromatin deregulation that can potentially lead to cancer. Our findings suggest that conventional detection methods, such as colonoscopy followed by histopathology, by itself, may be insufficient to reveal hidden or early tumors under development. We envision that this innovative work will provide new insights into LEM and support existing tools for early tumor detection in clinical diagnosis, and fundamental biological and biomedical research of chromatin changes at the biomolecular level of cancer development.