Label free visualization of amyloid plaques in Alzheimer's disease with polarization-sensitive photoacoustic Mueller matrix tomography

The formation of amyloid plaques in the cortical and hippocampal brain regions caused by abnormal deposition of extracellular amyloid \b{eta}-protein (A\b{eta}) is a characteristic pathological hallmark of early Alzheimer's disease (AD), while label-free graphic rendering of diseased amyloid plaques in vivo is still a highly challenging task. Herein, by ingeniously extracting the polarization-sensitive optical absorption of amyloid plaques via photoacoustic (PA) technique, a novel PA Mueller matrix (PAMM) tomography that capable of providing three new conformational parameters of molecules is developed to realize depth-resolved label-free imaging of amyloid plaques. Whole brain PAMM imaging on different stages of APP/PS1 transgenic AD mice has been performed to demonstrate its ability for in situ/in vivo quantitative three-dimensional (3D) detection of amyloid plaques and its great potential for monitoring early AD pathological development without labeling.