Dataset Information

Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis.

ABSTRACT: While metabolic changes are considered a cancer hallmark, their assessment has not been incorporated in the detection of early or precancers, when treatment is most effective. Here, we demonstrate that metabolic changes are detected in freshly excised human cervical precancerous tissues using label-free, non-destructive imaging of the entire epithelium. The images rely on two-photon excited fluorescence from two metabolic co-enzymes, NAD(P)H and FAD, and have micron-level resolution, enabling sensitive assessments of the redox ratio and mitochondrial fragmentation, which yield metrics of metabolic function and heterogeneity. Simultaneous characterization of morphological features, such as the depth-dependent variation of the nuclear:cytoplasmic ratio, is demonstrated. Multi-parametric analysis combining several metabolic metrics with morphological ones enhances significantly the diagnostic accuracy of identifying high-grade squamous intraepithelial lesions. Our results motivate the translation of such functional metabolic imaging to in vivo studies, which may enable improved identification of cervical lesions, and other precancers, at the bedside.

SUBMITTER: Pouli D

PROVIDER: S-EPMC7311071 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis.

Pouli Dimitra D Thieu Hong-Thao HT Genega Elizabeth M EM Baecher-Lind Laura L House Michael M Bond Brian B Roncari Danielle M DM Evans Megan L ML Rius-Diaz Francisca F Munger Karl K Georgakoudi Irene I

Cell reports. Medicine 20200501 2

While metabolic changes are considered a cancer hallmark, their assessment has not been incorporated in the detection of early or precancers, when treatment is most effective. Here, we demonstrate that metabolic changes are detected in freshly excised human cervical precancerous tissues using label-free, non-destructive imaging of the entire epithelium. The images rely on two-photon excited fluorescence from two metabolic co-enzymes, NAD(P)H and FAD, and have micron-level resolution, enabling se ...[more]

PMID: 32577625

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Project description:BackgrouundFor patients with any kind of atypical squamous intraepithelial lesion of the uterine cervix or vagina, colposcopy and punch biopsy are common procedures for histological determination following cytology. However, colposcopy-guided biopsy does not provide a high level of diagnostic accuracy. The aim of this study was to determine the usefulness of optical biopsy in vivo using endocytoscopy compared with conventional procedures using colposcopy.MethodsBetween May 2018 and March 2019, patients who were scheduled for cervical conization or mapping biopsies of the vagina were prospectively enrolled. Endocytoscopy was performed by senior endoscopists prior to scheduled procedures, and endocytoscopic images and biopsy samples were taken from the most prominent site and surrounding area of the cervical or vaginal lesions. The collection process of images was randomized and anonymous, and three doctors separately evaluated the images according to the ECA classification. ECA 4 and 5 are indicative of endoscopic malignancy. The primary endpoint was diagnostic accuracy (benign or malignant: cervical intraepithelial neoplasia (CIN) 3 or vaginal intraepithelial neoplasia (VAIN) 3 or worse) of cell images at the most prominent site in each patient.ResultsA total of 28 consecutive patients were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endocytoscopic images were 95.0% (84.8-98.6%), 87.5% (61.9-96.5%), 95.0% (84.8-98.6%), 87.5% (61.9-96.5%) and 92.9% (78.2-98.0%), respectively. Inter-observer agreement among three reviewers was 0.78 (0.08-9.88, P < 0.01). On the other hand, the accuracy of colposcopy-guided biopsy was 74.1% (64.0-84.0%).ConclusionsOptical cell diagnosis of cervical or vaginal intraepithelial neoplasia using endocytoscopy provides a high level of diagnostic accuracy.Trial registrationThe study was registered with the UMIN database (ID: 000031712 ). UMIN000031712 . Registered 16 March 2017.

Dataset Information

Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis.

Publications

Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis.

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