Calcium carbonate skeletons of scleractinian corals amplify light availability to their algal symbionts by diffuse scattering, optimizing photosynthetic energy acquisition. However, the mechanism of scattering and its role in coral evolution and dissolution of algal symbioses during “bleaching” events are largely unknown. Here we show that differences in skeletal fractal architecture at nano/micro-lengthscales within 96 coral taxa result in an 8-fold variation in light-scattering and considerably alter the algal light environment. We identified a continuum of properties that fall between two extremes: (1) corals with low skeletal fractality that are efficient at transporting and redistributing light throughout the colony with low scatter but are at higher risk of bleaching and (2) corals with high skeletal fractality that are inefficient at transporting and redistributing light with high scatter and are at lower risk of bleaching. While levels of excess light derived from the coral skeleton is similar in both groups, the low-scatter corals have a higher rate of light-amplification increase when symbiont concentration is reduced during bleaching, thus creating a positive feedback-loop between symbiont concentration and light-amplification that exposes the remaining symbionts to increasingly higher light intensities. By placing our findings in an evolutionary framework, in conjunction with a novel empirical index of coral bleaching susceptibility, we find significant correlations between bleaching susceptibility and light-scattering despite rich homoplasy in both characters; suggesting that the cost of enhancing light-amplification to the algae is revealed in decreased resilience of the partnership to stress.

Coherent backscattering (CBS) of light in random media has been previously investigated by use of coherent light sources. Here we report a novel method of CBS measurement that combines low spatial coherence, broadband illumination, and spectrally resolved detection. We show that low spatial coherence illumination leads to an anomalously broad CBS peak and a dramatic speckle reduction; the latter is further facilitated by low temporal coherence detection. Thus CBS can be observed in biological tissue and other media that previously were beyond the reach of conventional CBS measurements. We also demonstrate, for the first time to our knowledge, spectroscopic analysis of CBS. CBS spectroscopy may find important applications in probing random media such as biological tissue in which depth-selective measurements are crucial.

Field carcinogenesis detection represents a promising means for colorectal cancer (CRC) screening, although current techniques (e.g., flexible sigmoidoscopy) lack the requisite sensitivity. The novel optical technology low-coherence enhanced backscattering (LEBS) spectroscopy, allows identification of microscale architectural consequences of the field carcinogenesis in preclinical CRC models with unprecedented accuracy. To investigate the potential clinical translatability of this approach, we obtained biopsies from the normalappearing rectal mucosa from patients undergoing colonoscopy (n = 219). LEBS signals were recorded through a bench-top instrument. Four parameters characterizing LEBS signal were linearly combined into a single marker. We found that LEBS signal parameters generally mirrored neoplasia progression from patients with no neoplasia, to 5 to 9 mm adenoma and to advanced adenomas. The composite LEBS marker calculated from the LEBS signal paralleled this risk status (ANOVA P < 0.001). Moreover, this was independent of CRC risk factors, benign colonic findings, or clinically unimportant lesions (diminutive adenomas, hyperplastic polyps). For advanced adenomas, the LEBS marker had a sensitivity of 100%, specificity of 80%, and area under the receiver operator characteristic curve of 0.895. Leave-oneout cross-validation and an independent data set (n = 51) supported the robustness of these findings. In conclusion, we provide the first demonstration that LEBS-detectable alterations in the endoscopically normal rectum were associated with the presence of neoplasia located elsewhere in the colon. This study provides the proof of concept that rectal LEBS analysis may potentially provide a minimally intrusive CRC screening technique. Further studies with an endoscopically compatible fiber optic probe are under way for multicenter clinical validation. [Cancer Res 2009;69(10):4476-83]

Background: Increased premalignant epithelial microvascular blood content is a common theme in neoplastic transformation; however, demonstration of this phenomenon in colon carcinogenesis has been stymied by methodological limitations. Our group has recently developed a novel optics technology, four dimensional elastic light scattering fingerprinting (4D-ELF), which allows examination of the colonic mucosal architecture with unprecedented accuracy. In this study, we utilised 4D-ELF to probe the preneoplastic colonic microvasculature. Methods: Colonic mucosal blood content was assessed by 4D-ELF at serial preneoplastic time points from azoxymethane (AOM) treated Fisher 344 rats and age matched control animals. We also examined the pretumorigenic intestinal mucosa of the MIN mouse, and compared with wild-type mice. Finally, in a pilot study, we examined superficial blood content from the endoscopically normal mid transverse colon in 37 patients undergoing screening colonoscopy. Results: In the AOM treated rat model, augmentation of superficial mucosal and total mucosal/superficial submucosal blood supply preceded the appearance of aberrant crypt foci (ACF) and temporally and spatially correlated with future ACF occurrence. These findings were replicated in MIN mice. The 4D-ELF based results were corroborated with immunoblot analysis for haemoglobin on mucosal scrapings from AOM treated rats. Moreover, 4D-ELF analysis of normal human colonic mucosa indicated that there was a threefold increase in superficial blood in patients who harboured advanced adenomas. Conclusion: We report, for the first time, that blood content is increased in the colonic microvasculature at the earliest stages of colon carcinogenesis. These findings may provide novel insights into early biological events in colorectal carcinogenesis and have potential applicability for screening.

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...

There has been a significant interest in developing depth-selective optical interrogation of biological tissue in general and superficial (e.g. mucosal) tissue in particular. We report an in vivo polarization gating fiber-optic probe that obtains backscattering spectroscopic measurements from a range of near-surface depths (100µm -200µm). The design and testing was performed with polarized light Monte Carlo simulations and in tissue model experiments. We used the probe to investigate mucosal changes in early carcinogenesis. Measurements performed in the colonic mucosa of 125 human subjects provide the first in vivo evidence that mucosal blood supply is increased early in carcinogenesis not only in precancerous adenomatous lesions but also in the histologically normalappearing tissue surrounding these lesions. This effect was primarily limited to the mucosal microcirculation and was not present in the larger blood vessels located deeper in colonic tissue.

Background & Aims-We have previously utilized a novel biomedical optics technology, fourdimensional elastically-scattered light fingerprinting, to demonstrate that in experimental colon carcinogenesis, the predysplastic epithelial microvascular blood content is markedly elevated. In order to assess the potential clinical translatability of this putative field effect marker, we characterized the early increase in blood supply (EIBS) in humans in vivo.

The phenomenon of enhanced backscattering (also known as coherent backscattering), an object of substantial scientific interest, has awaited application to tissue optics for the past two decades. Here we demonstrate, for the first time to our knowledge, depth-resolved spectroscopic elastic light scattering measurements in tissue by use of low-coherence enhanced backscattering (LEBS). We achieve the depth resolution by exploiting the nature of the LEBS peak that contains information about a wide range of tissue depths. We further demonstrate that depth-resolved LEBS spectroscopy has the potential to identify the origin of precancerous transformations in the colon at an early, previously undetectable stage.