Cervical cancer is a significant cause of morbidity in the U.S. with approximately 12,200 new cases and 4,200 deaths from this disease each year. As a screening tool, cervical cytology (the Papanicolaou smear) can reduce morbidity by detecting precancerous lesions;but it cannot locate dysplastic regions of the cervix, a necessity for biopsy guidance and therapy. Currently, regions suspected to be dysplastic are found by colposcopy with aceto-whitening, but this is a subjective diagnostic with limited accuracy and wide variability. The goal of this research project is to develop a novel coherence imaging platform for practical detection of cervical dysplasia. Reaching this goal will improve diagnosis and understanding of disease development. Many optical techniques have been proposed for detecting pre-cancerous lesions in the cervix, but none has yet been widely adopted, due primarily to limited performance. While high resolution methods show good sensitivity, the need to manually scan a probe across the ectocervix limits utility. In comparison, wide area imaging approaches examine more tissue area, but show limited specificity. Here we propose to create an imaging platform based on a multi-modality approach, combining wide field imaging, using multiplexed low coherence interferometry (mLCI) for comprehensive cervical mapping, with high resolution, depth-resolved nuclear morphology measurements, using angle-resolved LCI(a/LCI) for highly sensitive detection of dysplasia. The long term objective of this research is to create multi-modal instrument to enable diagnosis of cervical dysplasia. The following Specific Aims are proposed. 1) Develop multiplexed LCI for mapping the epithelial types of the cervix. The mLCI probe will conduct wide area scans of the ectocervix to map the squamous-to- columnar transition zone (T-zone). A proof of principle study at Duke will validate the mLCI probe, followed by a broader study at UCSF. Data will be compared to colpophotography, the current standard for assessing the T-zone. 2) Adapt angle-resolved LCI for detection of cervical dysplasia. a/LCI can detect dysplastic lesions via depth resolved nuclear morphology measurements. An initial in vivo pilot study will be conducted using an existing prototype and an optimized instrument will be developed to scan the ectocervix without needing to reposition the probe. The instrument will be used for proof of principle studies at Duke and then validated in a broader study at UCSF. To assess accuracy, a/LCI nuclear morphology measurements will be compared to histopathological evaluation of co-registered physical biopsies. 3) Integration of mLCI and a/LCI into a single imaging platform. The integrated platform will enable wide area mLCI scans, to map the T-zone of the cervix and serve as a guide for a/LCI nuclear morphology measurements to identify dysplasia at selected points. The instrument will be used in a pilot study at Duke and then applied in a clinical field test at UCSF. The optical imaging measurements will be compared to digital colpophotography to validate the T-zone mapping and to co-registered physical biopsies to confirm alignment of nuclear morphology with histopathological tissue state.
The proposed research will develop new biophotonics methods for assessing the health and development of cervical epithelial tissues. There will be a direct benefit to public health by creating new methods of screening and surveillance for early stages of cervical cancer. In addition, by providing an alternative method to biopsies there may also be a benefit of more widespread screening.
|Steelman, Zachary A; Ho, Derek; Chu, Kengyeh K et al. (2017) Scanning system for angle-resolved low-coherence interferometry. Opt Lett 42:4581-4584|
|Ho, Derek; Drake, Tyler K; Smith-McCune, Karen K et al. (2017) Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology. Int J Cancer 140:1447-1456|
|Steelman, Zachary A; Eldridge, Will J; Weintraub, Jacob B et al. (2017) Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies. J Biophotonics 10:1714-1722|
|Zhao, Yang; Eldridge, Will J; Maher, Jason R et al. (2017) Dual-axis optical coherence tomography for deep tissue imaging. Opt Lett 42:2302-2305|
|Rinehart, Matthew T; Park, Han Sang; Walzer, Katelyn A et al. (2016) Hemoglobin consumption by P. falciparum in individual erythrocytes imaged via quantitative phase spectroscopy. Sci Rep 6:24461|
|Park, Han Sang; Rinehart, Matthew T; Walzer, Katelyn A et al. (2016) Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells. PLoS One 11:e0163045|
|Kim, Sanghoon; Heflin, Stephanie; Kresty, Laura A et al. (2016) Analyzing spatial correlations in tissue using angle-resolved low coherence interferometry measurements guided by co-located optical coherence tomography. Biomed Opt Express 7:1400-14|
|Rinehart, Matthew T; Park, Han Sang; Wax, Adam (2015) Influence of defocus on quantitative analysis of microscopic objects and individual cells with digital holography. Biomed Opt Express 6:2067-75|
|Ho, Derek; Drake, Tyler K; Bentley, Rex C et al. (2015) Evaluation of hybrid algorithm for analysis of scattered light using ex vivo nuclear morphology measurements of cervical epithelium. Biomed Opt Express 6:2755-65|
|Ho, Derek; Kim, Sanghoon; Drake, Tyler K et al. (2014) Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers. Biomed Opt Express 5:3292-304|