<i>In-vitro</i>and<i>in-vivo</i>characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice

Ni, Ruiqing; Villois, Alessia; Deán‐Ben, Xosé Luís; Chen, Zhenyue; Vaas, Markus; Stavrakis, Stavros; Shi, Gloria; deMello, Andrew J.; Ran, Chongzhao; Razansky, Daniel; Arosio, Paolo; Klohs, Jan

doi:10.1101/2020.10.27.353862

Cited by 3 publications

(11 citation statements)

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“…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.…”

Section: Non-invasive In Vivo Vmsot Of Pbb5 Uptake In the Mouse Brainmentioning

confidence: 99%

“…Simultaneous vMSOT and planar fluorescence imaging at pre-, during, and post i.v. bolus injection of PBB5 was performed using a previously established hybrid fluorescence and vMSOT system 52,53,[93][94][95] , consisting of an epi-fluorescence fiberscope and a vMSOT system capable of covering the entire brain. The FOV provided is approximately 10x10 mm 2 for epifluorescence imaging and 15×15×15 mm 3 for vMSOT imaging, while the achievable spatial resolution is approximately 40 μm and 130 μm for epi-fluorescence and vMSOT, respectively 53,59,88,96 .…”

Section: In Vivo Imaging With the Hybrid Fluorescence And Vmsot Systemmentioning

confidence: 99%

“…During the experiments, vMSOT images were reconstructed in real-time by using a graphics processing unit (GPU)-based implementation of a back-projection formula 52,53,97 . The reconstructed images were further processed off-line to unmix the bio-distribution of PBB5 53 .…”

Section: Vmsot Image Reconstruction and Multi-spectral Analysismentioning

confidence: 99%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Vagenknecht

Ono

Luzgin

et al. 2021

Preprint

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AimAbnormal tau accumulation plays an important role in tauopathy diseases such as Alzheimer’s disease and Frontotemporal dementia. There is a need for high-resolution imaging of tau deposits at the whole brain scale in animal models. Here, we demonstrate non-invasive whole brain imaging of tau-targeted PBB5 probe in P301L model of 4-repeat tau at 130 μm resolution using volumetric multi-spectral optoacoustic tomography (vMSOT).MethodsThe binding properties of PBB5 to 4-repeat K18 tau and Aβ42 fibrils were assessed by using Thioflavin T assay and surface plasmon resonance assay. We identified the probe PBB5 suitable for vMSOT tau imaging. The imaging performance was first evaluated using postmortem human brain tissues from patients with Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy. Concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and wild-type mice. Ex vivo measurements on excised brains along with multiphoton microscopy and immunofluorescence staining of tissue sections were performed for validation. The spectrally-unmixed vMSOT data was registered with MRI atlas for volume-of-interest analysis.ResultsPBB5 showed specific binding to recombinant K18 tau fibrils, Alzheimer’s disease brain tissue homogenate by competitive binding against [11C]PBB3 and to tau deposits (AT-8 positive) in post-mortem corticobasal degeneration and progressive supranuclear palsy brain. i.v. administration of PBB5 in P301L mice led to retention of the probe in tau-laden cortex and hippocampus in contrast to wild-type animals, as also confirmed by ex vivo vMSOT, epi-fluorescence and multiphoton microscopy results.ConclusionvMSOT with PBB5 facilitates novel 3D whole brain imaging of tau in P301L animal model with high-resolution for future mechanistic studies and monitoring of putative treatments targeting tau.

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Section: Non-invasive In Vivo Vmsot Of Pbb5 Uptake In the Mouse Brainmentioning

confidence: 99%

Section: In Vivo Imaging With the Hybrid Fluorescence And Vmsot Systemmentioning

confidence: 99%

Section: Vmsot Image Reconstruction and Multi-spectral Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Vagenknecht

Ono

Luzgin

et al. 2021

Preprint

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Multi-scale optoacoustic molecular imaging of brain diseases

Razansky

Klohs

2021

Eur J Nucl Med Mol Imaging

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The ability to non-invasively visualize endogenous chromophores and exogenous probes and sensors across the entire rodent brain with the high spatial and temporal resolution has empowered optoacoustic imaging modalities with unprecedented capacities for interrogating the brain under physiological and diseased conditions. This has rapidly transformed optoacoustic microscopy (OAM) and multi-spectral optoacoustic tomography (MSOT) into emerging research tools to study animal models of brain diseases. In this review, we describe the principles of optoacoustic imaging and showcase recent technical advances that enable high-resolution real-time brain observations in preclinical models. In addition, advanced molecular probe designs allow for efficient visualization of pathophysiological processes playing a central role in a variety of neurodegenerative diseases, brain tumors, and stroke. We describe outstanding challenges in optoacoustic imaging methodologies and propose a future outlook.

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

Vagenknecht

Luzgin

Ono³

et al. 2021

Preprint

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Background Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer’s disease and Frontotemporal dementia. High-resolution imaging of tau deposits at the whole-brain scale in animal disease models are highly desired. Herein, we approach this challenge by non-invasively imaging the brain of P301L mice of 4-repeat tau with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) at ~ 115 µm spatial resolution using tau-targeted pyridinyl-butadienyl-benzothiazole derivative PBB5 (i.v.). Results PBB5 showed specific binding to recombinant K18 tau fibrils by fluorescence assay, to post-mortem Alzheimer’s disease brain tissue homogenate by competitive binding against [11C]PBB3, and to tau deposits (AT-8 positive) in post-mortem corticobasal degeneration and progressive supranuclear palsy brains. Concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and non-transgenic littermate mice. A dose dependent optoacoustic and fluorescence signal intensity was observed in the mouse brains with i.v. administration of different concentrations of PBB5. i.v. administration of PBB5 in P301L mice showed higher retention in tau-laden cortex and hippocampus compared to wild-type, confirmed by ex vivo vMSOT, epi-fluorescence, multiphoton microscopy, immunofluorescence staining using AT-8 antibody for phosphorylated tau. Conclusions We demonstrated non-invasive 3D whole-brain imaging of tau in P301L mice with a vMSOT system using PBB5 at a previously unachieved ~ 115 µm spatial resolution. This platform provides new tool to study tau spreading and clearance in tauopathy mouse model, foreseeable in monitoring of tau targeting putative therapeutics.

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

Cited by 3 publications

References 62 publications

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

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

Multi-scale optoacoustic molecular imaging of brain diseases

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

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