Quantitative optical coherence microscopy of neuron morphology in human entorhinal cortex

INTRODUCTION: The size and shape of neurons are important features indicating aging and the pathology of neurodegenerative diseases. Despite the significant advances of optical microscopy, quantitative analysis of the neuronal features in the human brain remains largely incomplete. Traditional histology on thin slices bears tremendous distortions in three-dimensional reconstruction, the magnitude of which are often greater than the structure of interest. Recently development of tissue clearing techniques enable the whole brain to be analyzed in small animals; however, the application in the human remains challenging. METHODS: In this study, we present a label-free quantitative optical coherence microscopy (OCM) technique to obtain the morphological parameters of neurons in human entorhinal cortex (EC). OCM uses the intrinsic back-scattering property of tissue to identify individual neurons in 3D. The area, length, width, and orientation of individual neurons are quantified and compared between layer II and III in EC. RESULTS: The high-resolution mapping of neuron size, shape, and orientation shows significant differences between layer II and III neurons in EC. The results are validated by standard Nissl staining of the same samples. DISCUSSION: The quantitative OCM technique in our study offers a new solution to analyze variety of neurons and their organizations in the human brain, which opens new insights in advancing our understanding of neurodegenerative diseases.