Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis
Summary: 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 usi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379120300227 |
| _version_ | 1818523312360259584 |
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| author | Dimitra Pouli Hong-Thao Thieu Elizabeth M. Genega Laura Baecher-Lind Michael House Brian Bond Danielle M. Roncari Megan L. Evans Francisca Rius-Diaz Karl Munger Irene Georgakoudi |
| author_facet | Dimitra Pouli Hong-Thao Thieu Elizabeth M. Genega Laura Baecher-Lind Michael House Brian Bond Danielle M. Roncari Megan L. Evans Francisca Rius-Diaz Karl Munger Irene Georgakoudi |
| author_sort | Dimitra Pouli |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-11T05:43:29Z |
| format | Article |
| id | doaj.art-a1d21f7348d9425b9cad440ab9ecf788 |
| institution | Directory Open Access Journal |
| issn | 2666-3791 |
| language | English |
| last_indexed | 2024-12-11T05:43:29Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports Medicine |
| spelling | doaj.art-a1d21f7348d9425b9cad440ab9ecf7882022-12-22T01:19:04ZengElsevierCell Reports Medicine2666-37912020-05-0112100017Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia DiagnosisDimitra Pouli0Hong-Thao Thieu1Elizabeth M. Genega2Laura Baecher-Lind3Michael House4Brian Bond5Danielle M. Roncari6Megan L. Evans7Francisca Rius-Diaz8Karl Munger9Irene Georgakoudi10Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USADepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Pathology and Laboratory Medicine, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USADepartment of Preventive Medicine and Public Health, Faculty of Medicine, University of Málaga, 32 Louis Pasteur Boulevard, 29071 Málaga, SpainDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USADepartment of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379120300227Multiphoton microscopymetabolic imaginglabel-free imagingHPVcervical cancertranslational imaging |
| spellingShingle | Dimitra Pouli Hong-Thao Thieu Elizabeth M. Genega Laura Baecher-Lind Michael House Brian Bond Danielle M. Roncari Megan L. Evans Francisca Rius-Diaz Karl Munger Irene Georgakoudi Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis Cell Reports Medicine Multiphoton microscopy metabolic imaging label-free imaging HPV cervical cancer translational imaging |
| title | Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis |
| title_full | Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis |
| title_fullStr | Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis |
| title_full_unstemmed | Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis |
| title_short | Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis |
| title_sort | label free high resolution optical metabolic imaging of human cervical precancers reveals potential for intraepithelial neoplasia diagnosis |
| topic | Multiphoton microscopy metabolic imaging label-free imaging HPV cervical cancer translational imaging |
| url | http://www.sciencedirect.com/science/article/pii/S2666379120300227 |
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