Volumetric multispectral optoacoustic tomography of beta‐amyloid deposits in whole mouse brain

Abstract

AbstractBackgroundThe abnormal deposition of fibrillar beta‐amyloid deposits in the brain is one of the major histopathological hallmarks of Alzheimer’s disease. Currently 3D imaging using positron emission tomography for plaque visualization is of a limited resolution (1 mm) in relation to the size of mouse brain in widely used AD models.MethodWe developed a novel high‐resolution non‐invasive volumetric multi‐spectral optoacoustic tomography (vMSOT) of 100 mm resolution using amyloid probe AOI987 to visualize amyloid‐beta distribution in arcAβ and APP/PS1 transgenic mouse models of cerebral amyloidosis. Immunohistochemical staining was performed with AOI987, anti‐Aβ antibody 6E10 and fibrillar amyloid conformation antibody OC on mouse brain sections.Result In vivo vMSOT detects higher Aβ load in the cortex, hippocampus and thalamus of arcAβ mice, and in the cortex of APP/PS1 mice compared to non‐transgenic littermates, corresponding with immunohistochemical staining results in mouse brain sections. Confocal microscopy showed co‐localization of AOI987, 6E10 and OC to parenchymal and cerebral amyloid angiopathy in brain tissue sections from arcAb and APP/PS1 mice, thus verifying the specificity of the vMSOT amyloid imaging approach.ConclusionWe demonstrate a new high‐resolution in vivo 3D amyloid imaging platform across the murine brain in animal models of AD pathology, which facilitates mechanistic studies and the monitoring of putative treatments targeting Aβ.