Light Scattering from Collagen Fiber Networks: Micro-Optical Properties of Normal and Neoplastic Stroma

Arifler, Dizem; Pavlova, Ina; Gillenwater, Ann M.; Richards‐Kortum, Rebecca

doi:10.1529/biophysj.106.089839

Cited by 115 publications

(125 citation statements)

References 67 publications

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“…For example, high resolution imaging of collagen fibers has been achieved using confocal reflectance and fluorescence imaging. 9,23,32 Algorithms for three-dimensional reconstruction of collagen fibers have been developed. 9,32 This type of work is providing useful insights in the remodeling of the ECM during the development of early cancerous changes.…”

Section: Discussionmentioning

confidence: 99%

“…9,23,32 Algorithms for three-dimensional reconstruction of collagen fibers have been developed. 9,32 This type of work is providing useful insights in the remodeling of the ECM during the development of early cancerous changes. 9 However, so far these reconstructions have been limited to regions that extend only a few microns because they are computationally intensive.…”

Section: Discussionmentioning

confidence: 99%

“…9,32 This type of work is providing useful insights in the remodeling of the ECM during the development of early cancerous changes. 9 However, so far these reconstructions have been limited to regions that extend only a few microns because they are computationally intensive. A 2D Fourier-based analysis approach was developed and used to describe collagen remodeling by fibroblasts in the absence or presence of Rho kinase.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8] For example, changes in the organization and crosslinking or content of collagen are characteristic of cancerous transformations. [9][10][11][12] Therefore, it is important to develop quantitative methods that can provide detail with regards to the content, organization, and dynamic remodeling of collagen fibers.…”

Section: Introductionmentioning

confidence: 99%

“…19 The analytical tools that have been presented so far for characterizing collagen organization relied at least to a certain extent either on user input, 8,12,17,[19][20][21][22] or on computationally intense calculations that confine the region of interest to a limited region. 9 Here, we present the use of an adaptive thresholding approach in combination with Fourier-and a Hough-transform based analysis as a relatively simple and efficient means of acquiring quantitative information on the content, orientation, and local organization of collagen fibrils. The Fourier-transform-based approach is an established approach that has been used previously to characterize collagen organization, which relies on the autocorrelation of intensity fluctuations within an image and reports indirectly on the level of fiber alignment along a dominant direction within an image.…”

Section: Introductionmentioning

confidence: 99%

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Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels

Bayan

Levitt

Miller

et al. 2009

Journal of Applied Physics

109

124

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Collagen is the most prominent protein of human tissues. Its content and organization define to a large extent the mechanical properties of tissue as well as its function. Methods that have been used traditionally to visualize and analyze collagen are invasive, provide only qualitative or indirect information, and have limited use in studies that aim to understand the dynamic nature of collagen remodeling and its interactions with the surrounding cells and other matrix components. Second harmonic generation ͑SHG͒ imaging emerged as a promising noninvasive modality for providing high-resolution images of collagen fibers within thick specimens, such as tissues. In this article, we present a fully automated procedure to acquire quantitative information on the content, orientation, and organization of collagen fibers. We use this procedure to monitor the dynamic remodeling of collagen gels in the absence or presence of fibroblasts over periods of 12 or 14 days. We find that an adaptive thresholding and stretching approach provides great insight to the content of collagen fibers within SHG images without the need for user input. An additional feature-erosion and feature-dilation step is useful for preserving structure and noise removal in images with low signal. To quantitatively assess the orientation of collagen fibers, we extract the orientation index ͑OI͒, a parameter based on the power distribution of the spatial-frequency-averaged, two-dimensional Fourier transform of the SHG images. To measure the local organization of the collagen fibers, we access the Hough transform of small tiles of the image and compute the entropy distribution, which represents the probability of finding the direction of fibers along a dominant direction. Using these methods we observed that the presence and number of fibroblasts within the collagen gel significantly affects the remodeling of the collagen matrix. In the absence of fibroblasts, gels contract, especially during the first few days, in a manner that allows the fibers to remain mostly disoriented, as indicated by small OI values. Subtle changes in the local organization of fibers may be taking place as the corresponding entropy values of these gels show a small decrease. The presence of fibroblasts affects the collagen matrix in a manner that is highly dependent on their number. A low density of fibroblasts enhances the rate of initial gel contraction, but ultimately leads to degradation of collagen fibers, which start to organize in localized clumps. This degradation and reorganization is seen within the first days of incubation with fibroblasts at a high density and is followed by de novo collagen fiber deposition by the fibroblasts. These collagen fibers are more highly oriented and organized than the fibers of the original collagen gel. These initial studies demonstrate that SHG imaging in combination with automated image analysis approaches offer a noninvasive and easily implementable method for characterizing important features of the content and organization of collage...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels

Bayan

Levitt

Miller

et al. 2009

Journal of Applied Physics

109

124

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show abstract

Tissue Polarimetry

2015

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Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy

Cantor

Yamal

Guillaud

et al. 2010

Intl Journal of Cancer

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Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) 5 0.92-1.00] and an estimated specificity of 0.71 [95% CI 5 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI 5 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.Cervical cancer remains a major cause of morbidity and mortality in the developing world, where 85% of cancers arise. 1,2 Identification of cancerous and precancerous lesions at earlier stages, when interventions are more likely to be effective, is critical for effective cancer control. [3][4][5][6] Recent advances in fiber-optic and semiconductor technologies have enabled the development of a new generation of inexpensive, miniature optical sensors that can probe the interaction of light with potentially cancerous tissue in real-time. 7,8 Work to integrate this new technology with existing detection modalities and clinical screening efforts is ongoing.

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Light Scattering from Collagen Fiber Networks: Micro-Optical Properties of Normal and Neoplastic Stroma

Cited by 115 publications

References 67 publications

Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels

Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels

Tissue Polarimetry

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy

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