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

Vagenknecht, Patrick; Luzgin, Artur; Ono, Masahiro; Ji, Bin; Higuchi, Makoto; Noaín, Daniela; Maschio, Cinzia; Sobek, Jens; Chen, Zhenyue; Konietzko, Uwe; Gerez, Juan; Riek, Roland; Razansky, Daniel; Klohs, Jan; Nitsch, Roger M.; Deán‐Ben, Xosé Luís; Ni, Ruiqing

doi:10.1007/s00259-022-05708-w

Cited by 33 publications

(26 citation statements)

References 103 publications

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“…93 ) from PMOD. VOI analysis of 15 brain regions was performed using the embedded Mouse VOI atlas (Ma-Benveniste-Mirrione) in PMOD as in standard microPET data analysis procedure 15,94 . Specifically, time course of regional AOI987 absorbance (a.u.)…”

Section: Co-registration With Mri and Volume-of-interest Analysis Of ...mentioning

confidence: 99%

Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice

Chen

Deán‐Ben

et al. 2022

Nat. Biomed. Eng

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Deposits of amyloid-β (Aβ) in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale, or via whole-brain images from modalities lacking the resolution or molecular specificity to accurately characterize Aβ pathologies. Here we show that large-field multifocal illumination fluorescence microscopy and panoramic volumetric multispectral optoacoustic tomography can be combined to longitudinally assess Aβ deposits in transgenic mouse models of Alzheimer's disease. We used fluorescent Aβ-targeted probes (the luminescent conjugated oligothiophene HS-169 and the oxazine-derivative AOI987) to transcranially detect Aβ deposits in the cortex of APP/PS1 and arcAβ mice with single-plaque resolution (8 μm) and across the whole brain (including the hippocampus and the thalamus, which are inaccessible by conventional intravital microscopy) at sub-150 μm resolutions. Two-photon microscopy, light-sheet microscopy and immunohistochemistry of brain-tissue sections confirmed the specificity and regional distributions of the deposits. High-resolution multiscale optical and optoacoustic imaging of Aβ deposits across the entire brain in rodents thus facilitates the in vivo study of Aβ accumulation by brain region and by animal age and strain.

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Section: Co-registration With Mri and Volume-of-interest Analysis Of ...mentioning

confidence: 99%

Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice

Chen

Deán‐Ben

et al. 2022

Nat. Biomed. Eng

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“… 250 Further, whole-brain targeted imaging of tau deposits, also a factor in diagnosing Alzheimer’s and dementia, was shown using pyridinyl-butadienyl-benzothiazole derivative PBB5. 251 An extensive review of molecular imaging of various brain diseases using PAI was recently published. 252 …”

Section: Molecular Photoacoustic Imagingmentioning

confidence: 99%

Looking deep inside tissue with photoacoustic molecular probes: a review

2022

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. Significance: Deep tissue noninvasive high-resolution imaging with light is challenging due to the high degree of light absorption and scattering in biological tissue. Photoacoustic imaging (PAI) can overcome some of the challenges of pure optical or ultrasound imaging to provide high-resolution deep tissue imaging. However, label-free PAI signals from light absorbing chromophores within the tissue are nonspecific. The use of exogeneous contrast agents (probes) not only enhances the imaging contrast (and imaging depth) but also increases the specificity of PAI by binding only to targeted molecules and often providing signals distinct from the background. Aim: We aim to review the current development and future progression of photoacoustic molecular probes/contrast agents. Approach: First, PAI and the need for using contrast agents are briefly introduced. Then, the recent development of contrast agents in terms of materials used to construct them is discussed. Then, various probes are discussed based on targeting mechanisms, in vivo molecular imaging applications, multimodal uses, and use in theranostic applications. Results: Material combinations are being used to develop highly specific contrast agents. In addition to passive accumulation, probes utilizing activation mechanisms show promise for greater controllability. Several probes also enable concurrent multimodal use with fluorescence, ultrasound, Raman, magnetic resonance imaging, and computed tomography. Finally, targeted probes are also shown to aid localized and molecularly specific photo-induced therapy. Conclusions: The development of contrast agents provides a promising prospect for increased contrast, higher imaging depth, and molecularly specific information. Of note are agents that allow for controlled activation, explore other optical windows, and enable multimodal use to overcome some of the shortcomings of label-free PAI.

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“…Ezura et al (2021) compared differential binding of [ 18 F]THK5351 to different tauopathies and found that high [ 18 F]THK5351 uptake was detected in the precentral and postcentral gyri of CBD patients, in the midbrain of PSP patients and in the parahippocampal gyri of AD patients compared to healthy controls, clearly distinguishing different tauopathies. In vivo imaging using [ 11 C]PBB3 showed the detection of tau inclusions in the brain stem of PS19 and cortical and hippocampal regions of the rTg4510 mouse model of FTD (Maruyama et al, 2013;Ishikawa et al, 2018;Ni et al, 2018;Vagenknecht et al, 2022). A disadvantage of radiolabeled [ 11 C]PBB3 is the insufficient dynamic range, clearance rate and off-target binding in the basal ganglia (Okamura et al, 2018).…”

Section: In Vivomentioning

confidence: 99%

Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer’s Disease and Other Tauopathies

Maschio

2022

Front. Aging Neurosci.

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The detection and staging of Alzheimer’s disease (AD) using non-invasive imaging biomarkers is of substantial clinical importance. Positron emission tomography (PET) provides readouts to uncover molecular alterations in the brains of AD patients with high sensitivity and specificity. A variety of amyloid-β (Aβ) and tau PET tracers are already available for the clinical diagnosis of AD, but there is still a lack of imaging biomarkers with high affinity and selectivity for tau inclusions in primary tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick’s disease (PiD). This review aims to provide an overview of the existing Aβ and tau PET imaging biomarkers and their binding properties from in silico, in vitro, and in vivo assessment. Imaging biomarkers for pathologic proteins are vital for clinical diagnosis, disease staging and monitoring of the potential therapeutic approaches of AD. Off-target binding of radiolabeled tracers to white matter or other neural structures is one confounding factor when interpreting images. To improve binding properties such as binding affinity and to eliminate off-target binding, second generation of tau PET tracers have been developed. To conclude, we further provide an outlook for imaging tauopathies and other pathological features of AD and primary tauopathies.

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

Cited by 33 publications

References 103 publications

Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice

Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice

Looking deep inside tissue with photoacoustic molecular probes: a review

Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer’s Disease and Other Tauopathies

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