High-Resolution Microendoscopy for the Detection of Cervical Neoplasia in Low-Resource Settings

Quinn, Mary Ellen; Bubi, Tefo Caddrouse; Pierce, Mark C.; Kayembe, Mukendi; Ramogola‐Masire, Doreen; Richards‐Kortum, Rebecca

doi:10.1371/journal.pone.0044924

Cited by 64 publications

(63 citation statements)

References 17 publications

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“…Normal squamous epithelium is characterized by regularly spaced, small nuclei. In contrast, the area of HSIL showed larger, more closely spaced nuclei, which is consistent with previous studies using high resolution microendoscopy to study squamous epithelium where increased nuclear density and nuclear size are observed and can be quantified in dysplastic tissue (13,14,31). The DSIMe images corresponding to the HSIL region showed improved image contrast.…”

Section: Resultssupporting

confidence: 90%

“…Improvements in image contrast enable improved recognition of nuclear morphometry, particularly in areas of precancer and cancer. Although visually compelling, the improved nuclear recognition could also improve automated algorithms designed to identify neoplasia in real time that would otherwise struggle in highly scattering tissue (14,32,33). Additionally, because DSIMe maintains the small size of the probe, this technique could be used to improve high resolution microendoscopy imaging in a wider array of tissues.…”

Section: Discussionmentioning

confidence: 99%

“…When used in conjunction with contrast agents, high resolution microendoscopy (HRME) has shown promise to improve early detection of precancerous lesions based on changes in nuclear size, shape, and density (9)(10)(11)(12)(13)(14)(15). However, the coherent fiber optic bundles used in microendoscopes lack inherent optical sectioning capabilities (8); out-of-focus light generated in highly scattering tissues can result in poor image contrast that obscures cellular detail (16,17), which is particularly problematic in tissues with glandular epithelium, such as the breast, where microendoscopic images do not show sufficient contrast to differentiate between normal and neoplastic tissue (18).…”

mentioning

confidence: 99%

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Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

Keahey

Ramalingam

Schmeler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Fiber optic microendoscopy has shown promise for visualization of molecular contrast agents used to study disease in vivo. However, fiber optic microendoscopes have limited optical sectioning capability, and image contrast is limited by out-of-focus light generated in highly scattering tissue. Optical sectioning techniques have been used in microendoscopes to remove out-of-focus light but reduce imaging speed or rely on bulky optical elements that prevent in vivo imaging. Here, we present differential structured illumination microendoscopy (DSIMe), a fiber optic system that can perform structured illumination in real time for optical sectioning without any opto-mechanical components attached to the distal tip of the fiber bundle. We demonstrate the use of DSIMe during in vivo fluorescence imaging in patients undergoing surgery for cervical adenocarcinoma in situ. Images acquired using DSIMe show greater contrast than standard microendoscopy, improving the ability to detect cellular atypia associated with neoplasia.

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

Keahey

Ramalingam

Schmeler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Phantoms were designed to simulate fluorescently labeled nuclei distributed at varying depths within scattering tissue, mimicking the proflavine-stained epithelium imaged in earlier HRME studies. The HRME has no optical sectioning ability with which to eliminate out-of-focus light when imaging thick tissue, but nevertheless can clearly delineate epithelial nuclei in normal and neoplastic tissues [26][27][28]. We showed here that the HRME system produces images of deep lying (defocused) objects with apparent diameters as predicted by a simple geometric model.…”

Section: Discussionmentioning

confidence: 86%

“…The simplicity, low cost, and real-time imaging performance of the HRME system have led to its use by several research groups in laboratory studies [11][12][13][14][15][16][17][18][19][20][21][22][23][24] and in vivo clinical investigations [25][26][27][28]. However, the imaging properties of the HRME system have not been fully characterized; in particular, the axial imaging range and sensitivity to out-of-focus light have to the best of our knowledge, not been quantitatively studied.…”

Section: Introductionmentioning

confidence: 99%

Axial response of high-resolution microendoscopy in scattering media

Koucky

Pierce

2013

Biomed. Opt. Express

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High-resolution microendoscopy (HRME) uses epi-fluorescence imaging with a coherent fiber-optic bundle to enable in vivo examination of cellular morphology. While the HRME platform has recently gained popularity as a simple alternative to confocal endomicroscopy, the axial response of HRME in thick, scattering tissue has yet to be described quantitatively. These details are important because when analyzing images collected by HRME, out-of-focus light may affect the accuracy of quantitative parameters such as nuclear-to-cytoplasm ratio, which has been proposed as a diagnostic indicator of dysplasia or cancer. In this study we investigated the imaging properties of the HRME system by using phantoms simulating scattering tissue with fluorescently labeled nuclei. We directly compared HRME imaging with confocal endomicroscopy in phantoms and in vivo human tissue. HRME images defocused (deep) objects with apparent diameters and intensity levels that are in agreement with a simple geometric model. Out-of-focus nuclei contribute a relatively low, uniform background level to images which neither leads to the erroneous appearance of large nuclei from deep layers, nor prevents accurate imaging of superficial nuclei with high contrast. Kortum, "A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer," Cancer Prev.

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Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology

Drake

Smith‐McCune

et al. 2017

Int. J. Cancer

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This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty (40) enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (> 0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis.

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High-Resolution Microendoscopy for the Detection of Cervical Neoplasia in Low-Resource Settings

Cited by 64 publications

References 17 publications

Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

Axial response of high-resolution microendoscopy in scattering media

Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology

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