A photonics localization method, called inverse participation ratio (IPR), is adeptly applied to elucidate the effects of probiotics and alcohol on colon cancer by quantifying the DNA molecular-specific spatial structural changes in colon cancer cell nuclei on a colon cancer mouse model via confocal imaging. The IPR light localization technique measures the degree of structural disorder of DNA molecular-specific spatial mass density fluctuations. The nuclear structural alterations in colon cancer cell nuclei have been known to begin at the nano-to-submicron level, which precedes and predicts more prominent microscopic observations later in the disease. The effects of probiotics on alcohol-treated colon cancer are not a well-understood problem. However, probiotics like Lactobacillus have proven effective in enhancing colon cell/tissue functions. The IPR study results show that alcohol treatment enhances colon cancer, and the treatment of probiotics on alcohol-treated colon cancer tries to bring colon cancer less severe to normal. We acknowledge the grant NIH- R21CA260147.
Among the deadliest diseases in human history, Alzheimer's disease (AD) is a chronic neurodegenerative disorder that increases in seriousness over time. Changes in the brain start several decades before the development of AD, as an abnormal protein, beta-amyloid, start aggregating in the hippocampus area of the brain. At an early stage of AD, structural changes occur at the nanoscale level due to intracellular structural alterations. Hence, detecting nanoscale-level abnormalities early in the disease process is crucial for effective treatment. Dual optical/photonic techniques, Partial wave spectroscopy (PWS), and inverse participation ratio (IPR), are used to detect the nano to submicron scales structural alterations in the human brain cells/tissues due to AD.
Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by degeneration of dopaminergic neurons in the substantia nigra of the midbrain and loss of both motor and non-motor features. We apply photonics techniques for the characterization of structural changes in brain cells/tissues in progressive PD. In particular, we use mesoscopic optical physics-based finer-focused partial wave spectroscopy (PWS) technique to quantify the nano to submicron scales structural alterations in the brain tissues. Initial results show a change in structural disorder (Ld) as well as in the nuclear DNA spatial mass density in brain tissues of PD patients due to density fluctuations.
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.
The quantitative measurement of nanoscale structural alterations in cells/tissues is important to understand their physical states. Molecular specific light localization technique and microscopic imaging are highly sensitive spectroscopic approaches for studying the structural abnormalities in brain cells under a sedative condition. Fetal alcohol syndrome and other neurological disorders are the severe, irreversible outcomes of fetal alcoholism. The alcohol consumed by a pregnant mother passes through the placenta to the growing womb and inhibits the growth of vital organs of the baby resulting in brain damage and other birth defects. This damage is initially at the nanoscale level in cells/tissue. We probe fetal alcoholic pup brain cells using dual spectroscopy approaches: 1) photonics localization method using inverse participation ratio via confocal imaging, confocal-IPR, to probe DNA and histone molecular spatial structural alterations; 2) a recently developed spectroscopic technique, partial wave spectroscopy (PWS), which combines mesoscopic physics with microscopic imaging and detects the nano to submicron scales alterations in pup’s brain cells/tissues. The molecular structural abnormalities calculated based on light localization properties show an increase in the degree of spatial molecular structural disorder in DNA and a decrease in histone. An increase in spatial disorder in DNA may suggest DNA unwinding while reduced structural disorder in histone may indicate the release of histone from the DNA and helps in the unwinding of the DNA and gene expression. This result is further supported by the PWS result which shows an increase in the degree of structural disorder in chronic alcohol-treated mice pup’s brain tissues.
Photonics localization due to light scattering is an important probe to understand the molecular specific structural changes in brain cells due to diseases or abnormalities. Chronic alcoholism is associated with medical, behavioral, and psychological problems including physical damage in brain cells/tissues. The effects of chronic alcoholism on brain cells/tissue structures at the nanoscale are not well understood. On the other hand, probiotic treatment has shown some reversing effect in curing the abnormalities in an alcoholic’s brain. In this work, we study the effect of probiotic, Lactobacillus Plantarum treatment on chronic alcoholic brain cells/tissues using a mouse model. We evaluate the light localization properties of molecular specific spatial mass density fluctuations based on mesoscopic physics-based inverse participation ratio via confocal imaging of cells, confocal-IPR technique. Using the technique, we probe overexpression of astrocyte and microglial cells, and chromatin structures of different brain cells, by probing molecular specific overexpression by staining the cells with appropriate dye/proteins and then calculating the degree of spatial molecular structural disorder (Ld). The confocal-IPR analysis of alcoholic astrocytes, microglia, and chromatin of the mice brain cells show an increase in the structural disorder indicating that alcohol has an adverse effect on different brain cells and nuclei. Whereas the normalcy in the structural disorder of these brain cells happens when probiotics were fed simultaneously with alcohol, confirms the improvement in chronic alcoholic brain health. The potential application of this novel approach to diagnosing the alcohol effect and probiotic treatment in the alcoholic brain is explored.
We report mesoscopic physics based nanoscale sensitive partial wave spectroscopy (PWS) study of the structural changes in brain hippocampal region due to chronic stress induced by a stress hormone in a mouse model. Our results show that the change in the average degree of structural disorder in hippocampal tissues from stressed hormone induced mice brains has a higher structural disorder value relative to that of controlled mice, and the change is in correlation with the duration of the stress. Furthermore, the structural changes are peaked around the mid hippocampal regions, both sides of the hippocampal tissues centering around the ventricle.
We present an open source electric field tracking Monte Carlo program to model backscattering in biological media containing birefringence, with computation of the coherent backscattering phenomenon as an example. These simulations enable the modeling of tissue scattering as a statistically homogeneous continuous random media under the Whittle-Matérn model, which includes the Henyey-Greenstein phase function as a special case, or as a composition of discrete spherical scatterers under Mie theory. The calculation of the amplitude scattering matrix for the above two cases as well as the implementation of birefringence using the Jones N-matrix formalism is presented. For ease of operator use and data processing, our simulation incorporates a graphical user interface written in MATLAB to interact with the underlying C code. Additionally, an increase in computational speed is achieved through implementation of message passing interface and the semi-analytical approach. Finally, we provide demonstrations of the results of our simulation for purely scattering media and scattering media containing linear birefringence.
The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, is a
spectacular manifestation of self-interference effects in elastic light scattering, which gives rise to an enhanced scattered
intensity in the backward direction. Although EBS has been the object of intensive investigation in non-biological
media over the last two decades, there have been only a few attempts to explore EBS for tissue characterization and
diagnosis. We have recently made progress in the EBS measurements of biological tissue by taking advantage of lowcoherence
(or partially coherent) illumination, which is referred to as low-coherence EBS (LEBS) of light. LEBS
possess novel and intriguing properties such as speckle reduction, self-averaging effect, broadening of the EBS width,
depth-selectivity, double scattering, and circular polarization memory effect. After we review the current state of
research on LEBS, we discuss how these characteristics apply for early cancer detection, especially in colorectal cancer
(CRC), which is the second leading cause of cancer mortality in the United States. Although colonoscopy remains the
gold standard for CRC screening, resource constraints and potential complications make it impractical to perform
colonoscopy on the entire population at risk (age > 50). Thus, identifying patients who are most likely to benefit from
colonoscopy is of paramount importance. We demonstrate that LEBS measurements in easily accessible colonoscopically normal mucosa (e.g., in the rectum of the colon) can be used for predicting the risk of CRC, and thus
LEBS has the potential to serve as accurate markers of the risk of neoplasia elsewhere in the colon.
The mechanisms of photon propagation in random media in the diffusive multiple scattering regime have been
previously studied using diffusion approximation. However, similar understanding in the low-order (sub-diffusion)
scattering regime is not complete due to difficulties in tracking photons that undergo very few scatterings events. Recent
developments in low-coherence enhanced backscattering (LEBS) overcome these difficulties and enable probing
photons that travel very short distances and undergo only a few scattering events. In LEBS, enhanced backscattering is
observed under illumination with spatial coherence length Lsc less than the scattering mean free path ls. In order to
understand the mechanisms of photon propagation in LEBS in the sub-diffusion regime, it is imperative to develop
analytical and numerical models that describe the statistical properties of photon trajectories. Here we derive the
probability distribution of penetration depth of LEBS photons and report Monte Carlo numerical simulations to support
our analytical results. Our results demonstrate that, surprisingly, the transport of photons that undergo low-order
scattering events has only weak dependence on the optical properties of the medium (ls and anisotropy factor g) and
strong dependence on the spatial coherence length of illumination, Lsc relative to those in the diffusion regime. More
importantly, these low order scattering photons typically penetrate less than ls into the medium due to low spatial
coherence length of illumination and their penetration depth is proportional to the one-third power of the coherence
volume (i.e. [ls &pgr; L2s] 1/3).
The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, has been the object of intensive investigation in nonbiological media over the last two decades. However, there have been only a few attempts to explore EBS for tissue characterization and diagnosis. We have recently made progress in the EBS measurements in tissue by taking advantage of low spatial coherence illumination, which has led us to the development of low-coherence enhanced backscattering (LEBS) spectroscopy. In this work, we review the current state of research on LEBS. After a brief discussion of the basic principle of EBS and LEBS, we present an overview of the unique features of LEBS for tissue characterization, and show that LEBS enables depth-selective spectroscopic assessment of mucosal tissue. Then, we demonstrate the potential of LEBS spectroscopy for predicting the risk of colon carcinogenesis and colonoscopy-free screening for colorectal cancer (CRC).
Interference effects caused due to the coherent waves traveling in time reversed paths produces an enhanced backscattering (EBS) cone, which is known to be inversely proportional to the transport mean free path length (ls*) of a scattering media. In biological media, ls* (0.5-2mm) >> wavelength λ, results in an extremely small (~0.0010) angular width of the EBS cone making the experimental observation of such narrow peaks to be difficult. Hence, we developed a low coherence enhanced backscattering (LEBS) technique by combining the EBS measurements with low spatial coherence illumination and low temporal coherence detection. Low spatial coherence behaves as a spatial filter preventing longer path lengths and collects photons undergoing low orders of scattering. The experimental angular width of these LEBS peaks (~0.30) are more than 100 times the width of the peak predicted by conventional diffusion theory. Here we present a photon random walk model of LEBS cones obtained using Monte Carlo simulation to further our understanding on the unprecedented broadening of the LEBS peaks. In general, the exit angles of the scattered photons are not considered while modeling the time reversed interference phenomenon in diffusion regime. We show that these photon exit angles are sensitive to the low orders of scattering, which plays a significant role in modeling LEBS peaks when the spatial coherence length of the light source is much smaller than ls*. Our results show that the model is in good agreement with experimental data obtained at different low spatial coherence illumination.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.