Nonlinear Optics with Near-Infrared Excitation Enable Real-Time Quantitative Diagnosis of Human Cervical Cancers
- 1 September 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 80 (17), 3745-3754
- https://doi.org/10.1158/0008-5472.can-20-0348
Abstract
Histopathological analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histological diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an area under the curve ≥ 0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection.Keywords
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Funding Information
- AMED (JP18he0902001)
- Takeda Science Foundation
- Japan Society for the Promotion of Science (JP18K15080)
This publication has 32 references indexed in Scilit:
- Endoscopic Ultrasound–guided Fine-Needle Aspiration Biopsy Coupled With a KRAS Mutation Assay Using Allelic Discrimination Improves the Diagnosis of Pancreatic CancerJournal of Clinical Gastroenterology, 2015
- Quantification of collagen I in airway tissues using second harmonic generationJournal of Biomedical Optics, 2014
- Establishing the Diagnosis of Lung CancerSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2013
- 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer PrecursorsObstetrics & Gynecology, 2013
- Compact and efficient Cr:LiSAF lasers pumped by one single-spatial-mode diode: a minimal cost approachJournal of the Optical Society of America B, 2012
- Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structureNature Protocols, 2012
- Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissueProceedings of the National Academy of Sciences of the United States of America, 2011
- 3D microscopy of transparent objects using third‐harmonic generationJournal of Microscopy, 1998
- Natural History of Cervical Intraepithelial NeoplasiaInternational Journal of Gynecological Pathology, 1993
- Weighted kappa: Nominal scale agreement provision for scaled disagreement or partial credit.Psychological Bulletin, 1968