Terahertz Imaging and Electromagnetic Model of Axon Demyelination in Alzheimer's Disease

We investigate the utility of terahertz (THz) spectroscopy in identifying Alzheimer's disease in human brain tissue. Using reflection-mode time-domain THz spectroscopy, two-dimensional images of formalin-fixed and paraffin-embedded tissue samples of the hippocampus area were recorded in the 60 GHz-2 THz band. The THz images were compared with microscopic images of the same samples after hematoxylin and eosin staining. We demonstrate that the THz reflection spectra, particularly from white matter, reveal detectable differences between postmortem brain tissues exhibiting Alzheimer's disease and normal controls. The THz reflectivity of white matter areas was on average 4.2% higher than that of gray matter regions in tissue samples with known Alzheimer's history, whereas for normal control samples the contrast was only 2%. Additional studies further enhance this hypothesis, and the demyelination of white matter in Alzheimer's tissues suggests a possible cause for the differences in the THz reflection spectra. We also compare the THz response of the tissues with conventional Luxol-fast blue staining to demonstrate the correlation between the two methods for predicting demyelination. In addition, we present a simplified electromagnetic model of white matter axons exhibiting various degrees of demyelination to further support this hypothesis through full-wave electromagnetic simulations. This study offers, for the first time, proof of concept for the feasibility of detecting Alzheimer's disease using THz spectroscopy on ex vivo samples.