Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy

Massalimova, Aidana; Ni, Ruiqing; Nitsch, Roger M.; Reisert, Marco; Elverfeldt, Dominik von; Klohs, Jan

doi:10.1159/000515754

Cited by 19 publications

(12 citation statements)

References 56 publications

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“…Imaging of GSK-3β also indicated a sex difference in P301L mouse model with difference in tracer uptake only between male P301L and wild-type mice (Knight et al, 2021). In other studies, no behavioral, structural, and metabolic difference was observed in the P301S (Criver.com, 2021) and P301L mice (Ni et al, 2020;Massalimova et al, 2021). Several histology and behavior studies in 3 × Tg mice have also indicated a higher amyloid load in female mice compared to male mice, while no difference in tau level between groups (Hirata-Fukae et al, 2008;Carroll et al, 2010;Yang et al, 2018).…”

Section: Imaging Microglia Activation and Astrocytosismentioning

confidence: 87%

Positron Emission Tomography in Animal Models of Tauopathies

Cao

Kong

et al. 2022

Front. Aging Neurosci.

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The microtubule-associated protein tau (MAPT) plays an important role in Alzheimer’s disease and primary tauopathy diseases. The abnormal accumulation of tau contributes to the development of neurotoxicity, inflammation, neurodegeneration, and cognitive deficits in tauopathy diseases. Tau synergically interacts with amyloid-beta in Alzheimer’s disease leading to detrimental consequence. Thus, tau has been an important target for therapeutics development for Alzheimer’s disease and primary tauopathy diseases. Tauopathy animal models recapitulating the tauopathy such as transgenic, knock-in mouse and rat models have been developed and greatly facilitated the understanding of disease mechanisms. The advance in PET and imaging tracers have enabled non-invasive detection of the accumulation and spread of tau, the associated microglia activation, metabolic, and neurotransmitter receptor alterations in disease animal models. In vivo microPET studies on mouse or rat models of tauopathy have provided significant insights into the phenotypes and time course of pathophysiology of these models and allowed the monitoring of treatment targeting at tau. In this study, we discuss the utilities of PET and recently developed tracers for evaluating the pathophysiology in tauopathy animal models. We point out the outstanding challenges and propose future outlook in visualizing tau-related pathophysiological changes in brain of tauopathy disease animal models.

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Section: Imaging Microglia Activation and Astrocytosismentioning

confidence: 87%

Positron Emission Tomography in Animal Models of Tauopathies

Cao

Kong

et al. 2022

Front. Aging Neurosci.

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“…Magnetic resonance imaging (MRI) provides versatile highresolution structural, functional, and molecular image data with high soft tissue contrast such as T 1 , T 2 anatomical scans, functional connectivity by using fMRI, white matter integrity assessed by diffusion tensor imaging, blood-brain barrier integrity assessed by dynamic contrast enhanced MRI, cerebral perfusion measured by arterial spin labeling sequence, and molecular imaging using contrast agents (Judenhofer et al, 2008;Ni et al, 2019;Ni et al, 2020c;Massalimova et al, 2021). The structural information derived from MRI helps locate specific molecular information provided by OA tomography after registration.…”

Section: Oa/magnetic Resonance Imagingmentioning

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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“…Structural MRI for assessing the neurodegeneration (brain atrophy) in the ATN framework has offered a valuable tool for early and differential diagnosis of AD and for disease staging [ 4 , 6 ]. Moreover, multiplex MRI sequences, such as diffusion tensor imaging (DTI) for white matter integrity assessment, resting-state (rs) functional MRI for functional connectivity analysis [ 7 , 8 ], as well as arterial spin labeling (ASL) for cerebral perfusion measurement, have emerged as potential diagnostic biomarkers for AD.…”

Section: Introductionmentioning

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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Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy

Cited by 19 publications

References 56 publications

Positron Emission Tomography in Animal Models of Tauopathies

Positron Emission Tomography in Animal Models of Tauopathies

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals

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

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