As cancer progresses, macromolecules, such as DNA, RNA or lipids, inside cells undergo spatial structural rearrangements and alterations. Mesoscopic light transport-based optical partial wave spectroscopy (PWS) was recently introduced to quantify changes in the nanoscale structural disorder in biological cells. The PWS measurement is performed using a parameter termed as "disorder strength" (L ), which represents the degree of nanoscale structural disorder inside the cells. It was shown that cancerous cells have higher disorder strength than normal cells. In this work, we first used the PWS to analyze the hierarchy of different types of prostate cancer cells, namely, C4-2, DU-145 and PC-3, by quantifying their average disorder strengths. Results expectedly showed that L values increases in accordance with the increasing aggressiveness/tumorigenicity levels of these cells. Using the L parameter, we then analyzed the chemoresistance properties of these prostate cancer cells to docetaxel drug compared to their chemosensitivity. Results show that chemoresistant cancer cells have increased L values, that is, higher disorder strength, relative to chemosensitive cancer cells. Thus, use of the L metric can be effective in determining the efficacy of particular chemotherapy.

Chronic stress affects nano to microscale structures of the brain cells/tissues due to suppression of neural growths and reconnections, hence the neuronal activities. This results in depression, memory loss and even death of the brain cells. Our recently developed novel optical technique, partial wave spectroscopic microscopy has nanoscale sensitivity, and hence, can detect nanoscale changes in brain tissues due to stress. In this study, we applied this technique to quantify the stress related structural changes in the corticosterone‐treated mouse model of stress. Our results show that brains from corticosterone‐treated mice showed higher nanoscale structural disorder in the hippocampal region as compared to the brain from normal (vehicle) mice. The increase in structural alteration correlates with the duration of the stress. We further quantified the relative changes and the spatial localization of these changes in this mouse model and found out that the maximum changes occurred nearly symmetrically in both regions of the hippocampus. The mRNA for stress‐related genes, brain‐derived neurotrophic factor and tyrosine kinase‐coupled receptor were also significantly reduced in the hippocampus of corticosterone‐treated mice compared to that in control mice. These results indicate that chronic corticosterone treatment induces nanoscale structural alterations in mouse brain that corresponds to changes in stress‐related gene expression.

Cancer is an epidemic worldwide. At present one in four persons has cancer and this statistic will change to one in a two person in the near future. It is now known that war against cancer is the early, curable detection and treatment. Affordable, quick and easy detection methods are, therefore, essential. Standard pathologist way of detecting cancer is looking at the stained biopsy tissue samples under microscope, brings lots of human error. A tissue is a spatial heterogeneous medium and it has fractal properties due to its self-similarity in mass distribution. It is now known that with the progress of cancer the tissue heterogeneity changes due to more mass accumulations and rearrangement of intracellular macromolecules such as DNA and lipids etc. Furthermore, there are tissue micro array (TMA) samples available that provides array of hundred samples in one glass slides. In this study, using reflectance microscopy we have analyzed the fractal dimension of 5µm colon TMA samples to correctly distinguish between normal, adjacent to cancer, benign, stage-1 and stage-2 colon cancers. This fractal property of the tissues is also supported by entropy and spatial correlation calculations. The application of this method for diagnostic applications is also discussed.

. Significance: Light is a good probe for studying the nanoscale-level structural or molecular-specific structural properties of brain cells/tissue due to stress, alcohol, or any other abnormalities. Chronic alcoholism during pregnancy, i.e., fetal alcoholism, being teratogenic, results in fetal alcohol syndrome, and other neurological disorders. Understanding the nano-to-submicron scale spatial structural properties of pup brain cells/tissues using light/photonic probes could provide a plethora of information in understanding the effects of fetal alcoholism. Aim: Using both light scattering and light localization techniques to probe alterations in nano- to-submicron scale mass density or refractive index fluctuations in brain cells/tissues of mice pups, exposed to fetal alcoholism. Approach: We use the mesoscopic physics-based dual spectroscopic imaging techniques, partial wave spectroscopy (PWS) and molecular-specific inverse participation ratio (IPR) using confocal imaging, to quantify structural alterations in brain tissues and chromatin/histone in brain cells, respectively, in 60 days postnatal mice pup brain, exposed to fetal alcoholism. Results: The finer focusing PWS analysis on tissues shows an increase in the degree of structural disorder strength in the pup brain tissues. Furthermore, results of the molecular-specific light localization IPR technique show an increase in the degree of spatial molecular mass density structural disorder in DNA and a decrease in the degree in histone. Conclusions: In particular, we characterize the spatial pup brain structures from the molecular to tissue levels and address the plausible reasons for such as mass density fluctuations in fetal alcoholism.

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