In-vitro and in-vivo 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:10.1016/j.pacs.2021.100285

Cited by 38 publications

(29 citation statements)

References 73 publications

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“…The advantage of MRI molecular imaging stems from its superior resolution and improved signal-to-noise ratio, enabled by the development in high-field MRI and coil arrays. MRI provides versatile functional, structural, and molecular readouts and longitudinal, large field-of-view imaging capacity compared to other imaging modalities, such as two-photon microscopy, fluorescence molecular tomography, and optoacoustic microscopy [ 225 , 226 , 227 , 228 , 229 , 230 ]. The disadvantages and limitations of preclinical MRI methods include the following:…”

Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

2021

IJMS

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Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.

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Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

2021

IJMS

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“…During the experiments, vMSOT images were reconstructed in real time by using a graphics processing unit (GPU)-based implementation of a back-projection formula [52,53,72]. The reconstructed images were further processed offline to unmix the biodistribution of PBB5 [53].…”

Section: Vmsot Image Reconstruction and Multi-spectral Analysismentioning

confidence: 99%

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

Section: Introductionmentioning

confidence: 99%

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

Vagenknecht

Luzgin

Ono

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose 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 is highly desired. Methods We approached this challenge by non-invasively imaging the brains of P301L mice of 4-repeat tau with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) at ~ 115 μm spatial resolution using the tau-targeted pyridinyl-butadienyl-benzothiazole derivative PBB5 (i.v.). In vitro probe characterization, concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and wild-type mice, followed by ex vivo validation using AT-8 antibody for phosphorylated tau. 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. Dose-dependent optoacoustic and fluorescence signal intensities were observed in the mouse brains following i.v. administration of different concentrations of PBB5. In vivo vMSOT brain imaging of P301L mice showed higher retention of PBB5 in the tau-laden cortex and hippocampus compared to wild-type mice, as confirmed by ex vivo vMSOT, epi-fluorescence, multiphoton microscopy, and immunofluorescence staining. Conclusions We demonstrated non-invasive whole-brain imaging of tau in P301L mice with vMSOT system using PBB5 at a previously unachieved ~ 115 μm spatial resolution. This platform provides a new tool to study tau spreading and clearance in a tauopathy mouse model, foreseeable in monitoring tau targeting putative therapeutics.

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“…OA tomography using oxazine derivative AOI987 has been shown to provide transcranial visualization of the bio-distribution of amyloid-β deposits in mouse models of AD amyloidosis (arcAβ and APP/PS1 model) ( Ni et al, 2020a ). A similar design using OA tomography with curcumin derivative CRANAD-2 in has been used in an arcAβ mouse model ( Ni et al, 2021 ). OA microscopy with Congo red has been used for the detection of amyloid-β plaques and cerebral amyloid angiopathy in the APP/PS1 mouse model ( Hu et al, 2009 ; Zhou et al, 2021 ).…”

Section: Hybrid Contrast Agents For Multimodal Oa Brain Imagingmentioning

confidence: 99%

“…The detection depth of OA ranges from millimeters to centimeters, which associates with spatial resolution (from <1 μm in OA microscopy to 100 μm in OA tomography) ( Li et al, 2017 ; Zhang et al, 2019a ; Li et al, 2020 ). Recent OA tomography has allowed imaging the whole mouse brain with <100 µm spatial resolution in vivo ( Deán-Ben et al, 2016 ; Vaas et al, 2017 ; Gottschalk et al, 2019 ; Ni et al, 2020a ; Ni et al, 2021 ) which is around 10 times higher than the resolution achievable by using commercial small-animal microPET scanners ( Lancelot and Zimmer, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals

Shi

Kong

et al. 2021

Front. Bioeng. Biotechnol.

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Optoacoustic (photoacoustic) imaging has demonstrated versatile applications in biomedical research, visualizing the disease pathophysiology and monitoring the treatment effect in an animal model, as well as toward applications in the clinical setting. Given the complex disease mechanism, multimodal imaging provides important etiological insights with different molecular, structural, and functional readouts in vivo. Various multimodal optoacoustic molecular imaging approaches have been applied in preclinical brain imaging studies, including optoacoustic/fluorescence imaging, optoacoustic imaging/magnetic resonance imaging (MRI), optoacoustic imaging/MRI/Raman, optoacoustic imaging/positron emission tomography, and optoacoustic/computed tomography. There is a rapid development in molecular imaging contrast agents employing a multimodal imaging strategy for pathological targets involved in brain diseases. Many chemical dyes for optoacoustic imaging have fluorescence properties and have been applied in hybrid optoacoustic/fluorescence imaging. Nanoparticles are widely used as hybrid contrast agents for their capability to incorporate different imaging components, tunable spectrum, and photostability. In this review, we summarize contrast agents including chemical dyes and nanoparticles applied in multimodal optoacoustic brain imaging integrated with other modalities in small animals, and provide outlook for further research.

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

Cited by 38 publications

References 73 publications

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

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

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals

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