Publications and Research
Analysis of Imaging Database and Identifying Novel MRI Diffusion Abnormalities in Alzheimer’s Disease
Alzheimer's disease (AD) is presumably caused by two neuropathological protein markers: amyloid beta (Aβ) and neuro fibrillary tangles. Alzheimer’s Disease Neuroimaging Initiative (ADNI) collects high quality patient data from standardized clinical trials using Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and Cerebral Spinal Fluid (CSF) biomarkers to diagnose and evaluate the effectiveness of treatment for AD. MRI and PET screening for Alzheimer’s Disease aim to find structural, functional, and neurochemical abnormalities causing or caused by AD brain diffusion tensor imaging (DTI) and Resting State functional MRI (RSfMRI) are emerging AD MRI tools. Tau PET is a promising method for predicting cognitive abnormalities, more accurate than amyloid PET and MRI. To our knowledge, metal exchange among key bio metals like Fe, Cu, Mn, and Ca (transmetallation) has not yet been explored in neurobiology of AD. However, our research in carbohydrate and animal protein matrix (fruits and chicken eggs) has demonstrated transmetallation and chelation in such biological media. Exogenous chemical stress from radiology contact agents or environmental metallo-toxins could also alter homeostasis of brain bio metals. Iron transporter proteins in deep brain areas have been researched with little success in Alzheimer’s and Parkinson’s and their role in protein aggregation and oxidative stress, leading to neuronal loss is not clear. We not that when iron is shielded from bioreactions it is non-magnetic while if it takes part in metal exchange it could be in charged states that are paramagnetic. We hypothesize that changes in brain iron levels or brain iron electron charge states are reflected in magnetic susceptibility changes in white and gray matter leading to diffusion tract abnormalities in MRI of the AD brain. It is not possible to perform invasive biopsy and thus pathologically correlate iron or any other metal in AD brain with cognitive dysfunction in AD patients during their lifetime or even post-mortem since the disease is not in the presence or absence of the metals but presumably in the functional form of the propose biometals (Fe, Cu) in the neuro-biochemical pathway. Both diffusion MRI and magnetic susceptibility measurements to localize abnormal iron provide complementary information and are affected in AD. We have analyzed ADNI database for DTI abnormalities and have identified two parameters (Fractional Anisotropy and Mean Diffusivity) that show significant fluctuations only in the Fornix region with AD progression that we are modeling as presumably due to abnormal CSF dynamics.
This poster, second place winner for group projects, was presented at the 38th Semi-Annual Dr. Janet Liou-Mark Honors & Undergraduate Research Poster Presentation, May 4, 2023. Mentor: Prof. Subhendra Sarkar (Radiologic Technology).