Nanoscale Cellular Changes in Field Carcinogenesis Detected by Partial Wave Spectroscopy

Subramanian, Hariharan; Roy, Hemant K.; Pradhan, Prabhakar; Goldberg, Michael J.; Muldoon, Joseph P.; Brand, Randall E.; Sturgis, Charles D.; Hensing, Thomas A.; Ray, Daniel; Bogojevic, Andrej; Jameel, Mohammed; Chang, Jeen Soo; Backman, Vadim

doi:10.1158/0008-5472.can-08-3895

Cited by 125 publications

(138 citation statements)

References 38 publications

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“…10 Furthermore, PWS has detected increasing nuclear disorder strength among cells in clinical samples obtained from histologically normal mucosa as a function of decreasing distance from colon, lung, ovarian, and pancreatic cancer lesions. 12,19,20 Together, these studies demonstrate that higher nuclear disorder strength in cells is positively correlated with higher tumorigenic potential.…”

Section: Validation Of a Model System Of Metastatic Transition In Crcmentioning

confidence: 63%

“…These efforts have been fruitful in translational studies of patient cohorts exploring detection of cancers prior to alterations of cells and tissues that can be detected by histology. 12,19,20 These efforts represent a biophysical strategy to characterize cancer that can operate in tandem with assays to identify specific genomic and proteomic alterations in cancers. 10 The methodological approach of large-scale genomic/proteomic array studies and systems biology has elucidated the utility of simultaneously determining correlations among many genes and proteins expressed in cancerous cells to reveal signaling network topologies, feedback loops, and heterogeneity in genomic/ proteomic expression profiles underlying cancer.…”

Section: Introductionmentioning

confidence: 99%

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Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

et al. 2014

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Abstract. Cells contributing to the pathogenesis of cancer possess cytoplasmic and nuclear structural alterations that accompany their aberrant genetic, epigenetic, and molecular perturbations. Although it is known that architectural changes in primary and metastatic tumor cells can be quantified through variations in cellular density at the nanometer and micrometer spatial scales, the interdependent relationships among nuclear and cytoplasmic density as a function of tumorigenic potential has not been thoroughly investigated. We present a combined optical approach utilizing quantitative phase microscopy and partial wave spectroscopic microscopy to perform parallel structural characterizations of cellular architecture. Using the isogenic SW480 and SW620 cell lines as a model of pre and postmetastatic transition in colorectal cancer, we demonstrate that nuclear and cytoplasmic nanoscale disorder, micron-scale dry mass content, mean dry mass density, and shape metrics of the dry mass density histogram are uniquely correlated within and across different cellular compartments for a given cell type. The correlations of these physical parameters can be interpreted as networks whose nodal importance and level of connection independence differ according to disease stage. This work demonstrates how optically derived biophysical parameters are linked within and across different cellular compartments during the architectural orchestration of the metastatic phenotype.

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Section: Validation Of a Model System Of Metastatic Transition In Crcmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

et al. 2014

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“…In our most recent optical experiments, we show that the degree of nanoscale disorder increases with the degree of carcinogenesis for both control and precancerous cells ͑in cell lines, mouse model, and different organs in human studies, such as pancreas, colon, and lung͒. [8][9][10] These nanoscale changes may result from the rearrangements of DNA, RNA, lipids, or proteins. We want to verify and quantify these nanoscale changes as observed in optical studies by TEM.…”

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confidence: 99%

Quantification of nanoscale density fluctuations using electron microscopy: Light-localization properties of biological cells

Pradhan

Damania

Joshi

et al. 2010

Applied Physics Letters

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We report a study of the nanoscale mass-density fluctuations of heterogeneous optical dielectric media, including nanomaterials and biological cells, by quantifying their nanoscale light-localization properties. Transmission electron microscope images of the media are used to construct corresponding effective disordered optical lattices. Light-localization properties are studied by the statistical analysis of the inverse participation ratio ͑IPR͒ of the localized eigenfunctions of these optical lattices at the nanoscale. We validated IPR analysis using nanomaterials as models of disordered systems fabricated from dielectric nanoparticles. As an example, we then applied such analysis to distinguish between cells with different degrees of aggressive malignancy. © 2010 American Institute of Physics. ͓doi:10.1063/1.3524523͔Quantifying the degree of nanoscale disorder is a major research interest in characterizing the optical ͑electronic͒ properties of disordered condensed-matter systems. 1 Statistical properties, such as the mean and standard deviation ͑std͒, of the inverse participation ratio ͑IPR͒ of the spatially localized optical eigenfunctions of these optical systems are important quantitative measures of the degree of disorder of these lattices, where IPR of an eigenfunction E is defined as IPR= ͉͐E͑r͉͒ 4 dr ជ ͓in units of inverse area in two dimension ͑2D͔͒. 2,3 The average value of the IPR of a uniform lattice is a fixed universal number ͑ϳ2.5 in 2D͒, but the value increases with an increasing degree of disorder ͑or degree of localization͒. IPR has been well-studied in condensed-matter physics for characterizing the degree of disorder of homogeneous and heterogeneous media in a single parameter. [4][5][6] In this paper, we report the study of light-localization properties of biological cells by first constructing optical lattices of these cells via transmission electron microscopy ͑TEM͒ imaging 7 and then studying the statistical properties of IPR of the eigenfunctions of these lattices. In our most recent optical experiments, we show that the degree of nanoscale disorder increases with the degree of carcinogenesis for both control and precancerous cells ͑in cell lines, mouse model, and different organs in human studies, such as pancreas, colon, and lung͒. [8][9][10] These nanoscale changes may result from the rearrangements of DNA, RNA, lipids, or proteins. We want to verify and quantify these nanoscale changes as observed in optical studies by TEM.It has been shown that the optical refractive index ͑n͒ is linearly proportional to the local density ͑ ͒ of intracellular macromolecules for a majority of the scattering substances found in living cells, such as proteins, lipids, DNA, or RNA, i.e., n = n 0 + ⌬n = n 0 + ␣ , where n 0 is the refractive index of the medium, is the local concentration of solids, with ␣ ϳ 0.18. 11 Furthermore, we consider that the absorption of the contrast agent by the cell is linearly proportional to the total mass present in the thin cell voxel. Therefore, if TEM imaging is perfo...

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“…Because PWS is sensitive to nanoscale structure below the diffraction limit of traditional microscopy systems, including those used for wholeslide imaging, it can be used for minimally invasive cancer screening via the field effect. In previous clinical experiments, PWS has been shown to be effective at detecting tumors in multiple organ sites, including the lung, colon, esophagus, pancreas, prostate, etc [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Nanoscale refractive index fluctuations detected via sparse spectral microscopy

Chandler

Cherkezyan

Subramanian

et al. 2016

Biomed. Opt. Express

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Partial Wave Spectroscopic (PWS) Microscopy has proven effective at detecting nanoscale hallmarks of carcinogenesis in histologically normal-appearing cells. The current method of data analysis requires acquisition of a three-dimensional data cube, consisting of multiple images taken at different illumination wavelengths, limiting the technique to data acquisition on ~30 individual cells per slide. To enable high throughput data acquisition and whole-slide imaging, new analysis procedures were developed that require fewer wavelengths in the same 500-700nm range for spectral analysis. The nanoscale sensitivity of the new analysis techniques was validated (i) theoretically, using finite-difference time-domain solutions of Maxwell's equations, as well as (ii) experimentally, by measuring nanostructural alterations associated with carcinogenesis in biological cells.

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Nanoscale Cellular Changes in Field Carcinogenesis Detected by Partial Wave Spectroscopy

Cited by 125 publications

References 38 publications

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

Quantification of nanoscale density fluctuations using electron microscopy: Light-localization properties of biological cells

Nanoscale refractive index fluctuations detected via sparse spectral microscopy

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