Light localization properties of weakly disordered optical media using confocal microscopy: application to cancer detection

Abstract

We have developed a novel technique to quantify submicron scale mass density fluctuations in weakly disordered heterogeneous optical media using confocal fluorescence microscopy. Our method is based on the numerical evaluation of the light localization properties of an 'optical lattice' constructed from the pixel intensity distributions of images obtained with confocal fluorescence microscopy. Here we demonstrate that the technique reveals differences in the mass density fluctuations of the fluorescently labeled molecules between normal and cancer cells, and that it has the potential to quantify the degree of malignancy of cancer cells. Potential applications of the technique to other disease situations or characterizing disordered samples are also discussed.

Quantification of photonic localization properties of targeted nuclear mass density variations: Application in cancer‐stage detection

“…For the sake of completeness, a brief discussion on the IPR technique is presented in this article, while an elaborated details of the method and necessary background can be seen elsewhere [13][14][15][16]. Using breast and prostate cancer cell lines, we demonstrate that the quantification of submicron to micron scale structural changes in the targeted nuclear DNA of these cells, measured in terms of "disorder strength," efficiently quantifies the hierarchy of tumorigenicity levels in these cancerous cell lines.…”

“…As a result, the quantification of intracellular structural alterations is an area of major interest. In this regard, the recently developed mesoscopic physicsbased light localization analysis approach for analyzing structural changes in biological cells have shown promising results [13][14][15][16]. Local structural changes inside cells are usually analyzed through textural analysis using confocal images.…”

“…In confocal fluorescence microscopy, any particular molecule can be selectively targeted for imaging using specific fluorescent dyes. Therefore, if fluctuation in the RI is represented by dn(r)/n 0 , then dn(r)/n 0 / dI(r) CFM /<I > CFM , where <I > CFM and dI(r) CFM represent the average confocal intensity and the intensity fluctuation at position r in the confocal image [16]. It has been shown that the RI, n(r), inside a cell is linearly proportional to local mass density, ρ cell (r), of macromolecules, for example DNA, RNA, lipids, etc., n(r) = n 0 + dn(r) = <ρ > cell + kdρ cell (r) [17,18], where n 0 is the average RI, dn(r) and dρ cell (r) represents RI and mass density fluctuations at position r, respectively; k is the proportionality constant.…”

“…Therefore, multiple length scales with different types of spatial correlation decay functional forms and length scales must be considered in order to accurately characterize the system. In this regard, the recently developed mesoscopic physicsbased light localization analysis approach for analyzing structural changes in biological cells have shown promising results [13][14][15][16]. This technique allows to quantify the degree of intracellular structural alterations by taking into account all types of spatial structural statistical correlation properties of refractive index (RI) distribution in single parameter, providing an easy comparison of the changing heterogeneous media.…”

“…Using breast and prostate cancer cell lines, we demonstrate that the quantification of submicron to micron scale structural changes in the targeted nuclear DNA of these cells, measured in terms of "disorder strength," efficiently quantifies the hierarchy of tumorigenicity levels in these cancerous cell lines. For the sake of completeness, a brief discussion on the IPR technique is presented in this article, while an elaborated details of the method and necessary background can be seen elsewhere [13][14][15][16].…”