Whole brain optoacoustic tomography reveals strain-specific regional beta-amyloid densities in Alzheimer’s disease amyloidosis models

Abstract

Deposition of beta-amyloid (Aβ) deposits is one major histopathological hallmark of Alzheimer's disease (AD). Here, we introduce volumetric multi-spectral optoacoustic tomography (vMSOT), which covers 10×10×10 mm 3 field-of-view, capable of 3D whole mouse brain imaging. We show for the first time the optoacoustic properties of oxazine-derivative AOI987 probe, which binds to Aβ, and the application of vMSOT for the quantification of brainwide Aβ deposition. Administration of AOI987 to two common transgenic mouse strains of AD amyloidosis led to a retention of the probe in Aβ-laden brain regions. Co-registered of vMSOT data to a brain atlas revealed strain-specific pattern of AOI987 uptake. A comparison with ex vivo light-sheet microscopy in cleared mouse brains showed a good correspondence in Aβ distribution. Lastly, we demonstrate the specificity of the AOI987 probe by immunohistochemistry. vMSOT with AOI987 facilitates preclinical brain region-specific studies of Aβ spread and accumulation, and the monitoring of putative treatments targeting Aβ.

In-vitroandin-vivocharacterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice

“…For hybrid imaging, the fiberscope was inserted into the central aperture of the spherical array detector. The system has an overall field-of-view of 15×15×15mm 3 and resolution in the 110 μm range for both vMSOT and epifluorescence measurements [32, 51]. The optoacoustic signals were recorded before injection, 20, 40, 60, 90 and 120 min after injection of CRANAD-2; fluorescence signals were recorded before injection, 22, 42, 62, 92 and 120 minutes after injection of CRANAD-2.…”

Optical Tissue Clearing: Illuminating Brain Function and Dysfunction

“…They discovered the early papillary body dysfunction and Aβ Papez circuit susceptibility in AD, which has not been found before 75 . Recently, the comparison of volumetric multispectral photoacoustic tomography (vMSOT) and optical clearing-based brain imaging has shown highly corresponding Aβ plaques 76 . In addition, the Aβ plaque-associated microenvironment also deserves attention to better understand Aβ development.…”

Non-invasive imaging of tau-targeted probe uptake by whole brain multi-spectral optoacoustic tomography

“…The set-up includes a custom-build hybrid imaging system with a fiberscopic insert (Fig. 2b) as described in detail elsewhere 52,53 . The vMSOT imaging data analysis pipeline consisted on the following steps.…”

“…Recently, volumetric multi-spectral optoacoustic tomography (vMSOT) imaging has been shown to provide previously unavailable capabilities to visualize the bio-distribution of amyloid-β (Aβ) deposits in mouse models of AD amyloidosis (arcAβ and APP/PS1) [52][53][54] . vMSOT capitalizes on the high sensitivity of optical contrast and the high resolution provided by ultrasound 55,56 , and can attain penetration depth of the whole mouse brain.…”

“…vMSOT capitalizes on the high sensitivity of optical contrast and the high resolution provided by ultrasound 55,56 , and can attain penetration depth of the whole mouse brain. State-of-the-art vMSOT embodiments enable whole-brain non-invasive imaging with 130 µm spatial resolution 52,53,[57][58][59][60][61][62] , i.e., almost an order of magnitude finer resolution compared to modern small-animal microPET scanners. In this study, we investigate on the capabilities of vMSOT assisted with the arylquinoline derivative PBB5 probe to enable in vivo high-resolution 3D transcranial mapping of tau across the entire mouse brain in 4R-tau P301L mouse models 26 .…”