SearcharxivSearch

arXiv subjects

Fatemah Alharthi

Publications and source records attributed to Fatemah Alharthi.

6 recordsLinked to original sources

Comprehensive Multimodal and Multiscale Analysis of Alzheimer Disease in 5xFAD Mice: Optical Spectroscopies, TEM, Neuropathological, and Behavioral Investigations

Alzheimer disease (AD) is considered one of the leading causes of death in the United States, and there is no effective cure for it. Understanding the neuropathological mechanisms underlying AD is essential for identifying early, reliable biomarkers and developing effective therapies. In this paper, we report on a comprehensive multimodal study of AD pathology using the 5xFAD mouse model. We employed light-scattering techniques, Partial Wave Spectroscopy (PWS) and Inverse Participation Ratio (IPR), to detect nanoscale structural alterations in brain tissues, nuclear components, and mitochondria. To support the light-scattering experiments, behavior, and histopathological studies were conducted. These analyses revealed significant increases in structural heterogeneity and mass density fluctuations in the brains of 5xFAD mice compared with Non-transgenic controls. Behavioral assessment demonstrated memory impairment in 5xFAD mice, reflected by a reduced recognition index. Histopathological analysis further revealed increased amyloid beta plaques and microglia activation in the hippocampus and cortex of 5xFAD mice compared with Non-transgenic controls. An increase in structural disorder within brain tissues can be attributed to higher mass density fluctuations, likely arising from macromolecular rearrangement driven by amyloid beta aggregation and neuroinflammatory responses as the disease progresses. Our findings suggest that PWS and IPR-derived metrics provide sensitive biophysical indicators of early cellular and subcellular disruption, offering potential as quantitative biomarkers for the detection and progression of AD.

physics.med-ph

Finer-Focused Partial Wave Spectroscopy (ff-PWS) and Detection of Cancer Stages From Human Tissue Samples

The progression of cancer is associated with different genetic and epigenetic events which result in nano to microscale structural alterations in cells/tissue. However, these structural alterations in the early stage of the disease remain undetectable by conventional microscopy due to the diffraction-limited resolution of ~200nm. With cancer being an epidemic worldwide, early and accurate detection methods are always in demand. In this sense, we developed a finer focusing mesoscopic physics-based partial wave spectroscopy (PWS) imaging and quantification technique, which can probe the precise scattering volume in cells/tissue to detect such structural alterations. Therefore, we employ the highly sensitive PWS technique to quantify the nanoscale refractive index fluctuations using commercially available paraffin embedded tissue microarrays (TMA) samples with the goal of the standardized early and accurate detection of stages of different cancers. Recently the use of scientific TMA samples has gained research interest in diagnosing different diseases and drug-effect in treatment since they are commercially easily accessible. In this work, deadly cancer such as pancreatic, prostate, breast, and colon cancer TMAs containing multiple cores of different stages for each cancer are analyzed using the PWS technique and the degree of disorder strength Ld was quantified. The finer focusing PWS results show that an increase in the disorder strength with the increase in the stage of each cancer. This quantitative analysis of different cancer stages using commercially available TMA samples could enhance and standardize early, accurate cancer diagnosis modalities.

physics.med-ph

Optical detection of the spatial structural alteration in the human brain tissues and cells and DNA and chromatin due to Parkinsons disease

Parkinsons disease (PD) is considered one of the most frequent neurological diseases in the world. There is a need to study the early and efficient biomarkers of Parkinsons, such as changes in structural disorders like DNA and chromatin, especially at the subcellular level in the human brain. We used two techniques, Partial wave spectroscopy (PWS) and Inverse Participation Ratio (IPR), to detect the changes in structural disorder in the human brain tissue samples. It was observed from the PWS experiment that there was an increase in structural disorder in Parkinsons disease tissues and cells when compared to normal tissues and cells using mesoscopic light transport theory. Furthermore, the IPR experiment also showed DNA and chromatin structural alterations that have the same trend and support the PWS results. The increase in mass density in the nuclei components, such as DNA and chromatin, can be linked to the aggregation of alpha-synuclein in the substantia nigra of the brain. This protein deposition is considered a significant cause of neuronal death in the brains of PD patients. We also did a histological analysis of brain tissues, which supports our results from dual photonics techniques. The results show that this dual technique is a powerful approach to detect the changes. Our results highlight the potential of the parameter, related to the structural disorder strength, as an efficient biomarker for PD progress, paving the way for research into early disease detection.

physics.med-ph

Dual Photonics Probing of Nano- to Submicron-Scale Structural Alterations in Human Brain Tissues or Cells and Chromatin or DNA with the Progression of Alzheimers Disease

Understanding alterations in structural disorders in tissue or cells or building blocks, such as DNA or chromatin in the human brain, at the nano to submicron level provides us with efficient biomarkers for Alzheimers detection. Here, we report a dual photonics technique to detect nano- to submicron-scale alterations in brain tissues or cells and DNA or chromatin due to the early to late progression of Alzheimers disease in humans. Using a recently developed mesoscopic light transport technique, fine-focused nano-sensitive partial wave spectroscopy (PWS), we measure the degree of structural disorder in tissues. Furthermore, the chemical-specific inverse participation ratio technique (IPR) was used to measure the DNA or chromatin structural alterations. The results of the PWS and IPR experiments showed a significant increase in the degree of structural disorder at the nano to submicron scale at different stages of AD relative to their controls for both the tissue or cell and DNA cellular levels. The increase in the structural disorder in cells or tissues and DNA or chromatin in the nuclei can be attributed to higher mass density fluctuations in the tissue and DNA or chromatin damage in the nuclei caused by the rearrangements of macromolecules due to the deposition of the amyloid beta protein and damage in DNA or chromatin with the progress of AD.

physics.med-ph

Photonics study of probiotic treatment on brain cells exposed to chronic alcoholism using molecular specific nuclear light localization properties via confocal imaging

Molecular specific photonics localization technique, the inverse participation ratio (IPR), is a powerful technique to probe the nanoscale structural alterations due to abnormalities or chronic alcoholism in brain cells using the confocal image. Chronic alcoholism is correlated with medical, behavioral, and psychological problems including brain cell damage. However, probiotics such as Lactobacillus Plantarum has shown the promising result in soothing the human brain. This report, using the Confocal-IPR technique, nano to submicron scale structural abnormalities of the glial cells and the nuclei of alcoholic mice brain in the presence of probiotics. The increase in the structural disorder of alcoholic brain cells while the decrease or normalcy in the structural disorder of brain cells of mice fed with probiotics and alcohol simultaneously indicates that alcohol stimulates probiotics and enhances brain function.

physics.bio-ph

Optical probing of pups brain tissue and molecular specific nuclear nano-structural alterations due to fetal alcoholism via dual spectroscopic approach

Mesoscopic physics-based dual spectroscopic imaging techniques, partial wave spectroscopy (PWS) and inverse participation ratio (IPR), are used to quantify the nano to submicron scales structural alterations in postnatal pups brain cells and tissues due to fetal alcoholism. Chronic alcoholism during pregnancy, being teratogenic, results in fetal alcohol syndrome and neurological disorder. Results of PWS studies of brain tissues show a higher degree of structural alterations. Furthermore, the IPR analyses of cell nuclei show that spatial molecular mass density structural disorder increases in DNA while decreases for histone. This study characterize the brain spatial structures from molecular to tissue level in fetal alcoholism.

physics.med-ph