Soma and Neurite Density MRI (SANDI) of the in-vivo mouse brain

Diffusion MRI (dMRI) provides unique insights into the neural tissue milieu by probing interaction of diffusing molecules and tissue microstructure. Most dMRI techniques focus on white matter tissues (WM) due to the relatively simpler modelling of diffusion in the more organized tracts; however, interest is growing in gray matter characterisations. The Soma and Neurite Density MRI (SANDI) methodology harnesses a model incorporating water diffusion in spherical objects (assumed to be associated with cell bodies) and in impermeable 'sticks' (representing neurites), which potentially enables the characterisation of cellular and neurite densities. Recognising the importance of rodents in animal models of development, aging, plasticity, and disease, we here sought to develop SANDI for preclinical imaging and provide a validation of the methodology by comparing its metrics with the Allen mouse brain atlas. SANDI was implemented on a 9.4T scanner equipped with a cryogenic coil, and experiments were carried out on N=6 mice. Pixelwise, ROI-based, and atlas comparisons were performed, and results were also compared to more standard Diffusion Kurtosis MRI (DKI) metrics. We further investigated effects of different pre-processing pipelines, specifically the comparison of magnitude and real-valued data, as well as different acceleration factors. Our findings reveal excellent reproducibility of the SANDI parameters, including the sphere and stick fraction as well as sphere size. More strikingly, we find a very good rank correlation between SANDI-driven soma fraction and Allen brain atlas contrast (which represents the cellular density in the mouse brain). Although some DKI parameters (FA, MD) correlated with some SANDI parameters in some ROIs, they did not correlate nearly as well as SANDI parameters with the Allen atlas, suggesting a much more specific nature of the SANDI parameters. We conclude that SANDI is a viable preclinical MRI technique that can greatly contribute to research on brain tissue microstructure.

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Understanding microstructure of the brain by comparison of neurite orientation dispersion and density imaging (NODDI) with transparent mouse brain

Acta Radiologica Open ◽

10.1177/2058460117703816 ◽

2017 ◽

Vol 6 (4) ◽

pp. 205846011770381 ◽

Cited By ~ 10

Author(s):

Kanako Sato ◽

Aurelien Kerever ◽

Koji Kamagata ◽

Kohei Tsuruta ◽

Ryusuke Irie ◽

...

Keyword(s):

Mouse Brain ◽

Fluorescent Protein ◽

Volume Fraction ◽

Anterior Commissure ◽

Yellow Fluorescent Protein ◽

Fiber Density ◽

Neurite Density ◽

Suitable Index ◽

The Brain

Background Neurite orientation dispersion and density imaging (NODDI) is a diffusion magnetic resonance imaging (MRI) technique with the potential to visualize the microstructure of the brain. Revolutionary histological methods to render the mouse brain transparent have recently been developed, but verification of NODDI by these methods has not been reported. Purpose To confirm the concordance of NODDI with histology in terms of density and orientation dispersion of neurites of the brain. Material and Methods Whole brain diffusion MRI of a thy-1 yellow fluorescent protein mouse was acquired with a 7-T MRI scanner, after which transparent brain sections were created from the same mouse. NODDI parameters calculated from the MR images, including the intracellular volume fraction (Vic) and the orientation dispersion index (ODI), were compared with histological findings. Neurite density, Vic, and ODI were compared between areas of the anterior commissure and the hippocampus containing crossing fibers (crossing areas) and parallel fibers (parallel areas), and the correlation between fiber density and Vic was assessed. Results The ODI was significantly higher in the crossing area compared to the parallel area in both the anterior commissure and the hippocampus ( P = 0.0247, P = 0.00022, respectively). Neurite density showed a similar tendency, but was significantly different only in the hippocampus ( P = 7.91E−07). There was no significant correlation between neurite density and Vic. Conclusion NODDI was verified by histology for quantification of the orientation dispersion of neurites. These results indicate that the ODI is a suitable index for understanding the microstructure of the brain in vivo.

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The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging

Magnetic Resonance in Medical Sciences ◽

10.2463/mrms.mp.2017-0031 ◽

2018 ◽

Vol 17 (2) ◽

pp. 138-144 ◽

Cited By ~ 7

Author(s):

Ryusuke Irie ◽

Koji Kamagata ◽

Aurelien Kerever ◽

Ryo Ueda ◽

Suguru Yokosawa ◽

...

Keyword(s):

Confocal Microscopy ◽

Mouse Brain ◽

Diffusion Tensor ◽

Diffusion Kurtosis Imaging ◽

Neurite Density ◽

Diffusion Kurtosis ◽

The Relationship ◽

And Diffusion

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Differential up-regulation of hypoxia-inducible vasoactive factors in fetal mouse brain in vivo upon intrauterine hypoxia

Neuropediatrics ◽

10.1055/s-2006-953623 ◽

2006 ◽

Vol 37 (03) ◽

Author(s):

R Trollmann ◽

K Strasser ◽

J Soliz ◽

D Wenzel ◽

W Rascher ◽

...

Keyword(s):

Mouse Brain ◽

Fetal Mouse ◽

Vasoactive Factors ◽

Intrauterine Hypoxia

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Lithium therapy in bipolar disorder is associated with higher in-vivo cortical neurite density

10.26226/morressier.5b68175eb56e9b005965c463 ◽

2018 ◽

Author(s):

Samuel Sarrazin

Keyword(s):

Bipolar Disorder ◽

Lithium Therapy ◽

Neurite Density

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Faculty Opinions recommendation of Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717950662.793455969 ◽

2012 ◽

Author(s):

Robert Abraham ◽

Naval Shanware

Keyword(s):

Mouse Brain ◽

Glucose Oxidation ◽

Tumor Metabolism

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Faculty Opinions recommendation of In vivo three-photon microscopy of subcortical structures within an intact mouse brain.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718303489.793492009 ◽

2014 ◽

Author(s):

Joe Fetcho

Keyword(s):

Mouse Brain ◽

Subcortical Structures ◽

Intact Mouse

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Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

Scientific Reports ◽

10.1038/s41598-021-85348-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoonhee Kim ◽

Yoon Bum Lee ◽

Seung Kuk Bae ◽

Sung Suk Oh ◽

Jong-ryul Choi

Keyword(s):

Ischemic Stroke ◽

Brain Damage ◽

Rabbit Model ◽

Specific Area ◽

Brain Atlas ◽

Rabbit Brain ◽

Stroke Model ◽

Triphenyltetrazolium Chloride ◽

Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

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1700 nm optical coherence microscopy enables minimally invasive, label-free, in vivo optical biopsy deep in the mouse brain

Light Science & Applications ◽

10.1038/s41377-021-00586-7 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Jun Zhu ◽

Hercules Rezende Freitas ◽

Izumi Maezawa ◽

Lee-way Jin ◽

Vivek J. Srinivasan

Keyword(s):

Minimally Invasive ◽

Mouse Brain ◽

Numerical Aperture ◽

Optical Biopsy ◽

Optical Coherence ◽

Label Free ◽

Optical Coherence Microscopy ◽

Minimal Invasiveness ◽

Cortical Regions

AbstractIn vivo, minimally invasive microscopy in deep cortical and sub-cortical regions of the mouse brain has been challenging. To address this challenge, we present an in vivo high numerical aperture optical coherence microscopy (OCM) approach that fully utilizes the water absorption window around 1700 nm, where ballistic attenuation in the brain is minimized. Key issues, including detector noise, excess light source noise, chromatic dispersion, and the resolution-speckle tradeoff, are analyzed and optimized. Imaging through a thinned-skull preparation that preserves intracranial space, we present volumetric imaging of cytoarchitecture and myeloarchitecture across the entire depth of the mouse neocortex, and some sub-cortical regions. In an Alzheimer’s disease model, we report that findings in superficial and deep cortical layers diverge, highlighting the importance of deep optical biopsy. Compared to other microscopic techniques, our 1700 nm OCM approach achieves a unique combination of intrinsic contrast, minimal invasiveness, and high resolution for deep brain imaging.

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Whole brain atlas-based diffusion kurtosis imaging parameters for evaluation of minimal hepatic encephalopathy

The Neuroradiology Journal ◽

10.1177/19714009211026924 ◽

2021 ◽

pp. 197140092110269

Author(s):

Prateek Gupta ◽

Sameer Vyas ◽

Teddy Salan ◽

Chirag Jain ◽

Sunil Taneja ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Clinical Symptoms ◽

Early Stage ◽

Imaging Techniques ◽

Clinical Stage ◽

Minimal Hepatic Encephalopathy ◽

Brain Atlas ◽

Diffusion Kurtosis Imaging ◽

Whole Brain ◽

Diffusion Kurtosis

Background and purposes Minimal hepatic encephalopathy (MHE) has no recognizable clinical symptoms, but patients have cognitive and psychomotor deficits. Hyperammonemia along with neuroinflammation lead to microstructural changes in cerebral parenchyma. Changes at conventional imaging are detected usually at the overt clinical stage, but microstructural alterations by advanced magnetic resonance imaging techniques can be detected at an early stage. Materials and methods Whole brain diffusion kurtosis imaging (DKI) data acquired at 3T was analyzed to investigate microstructural parenchymal changes in 15 patients with MHE and compared with 15 age- and sex-matched controls. DKI parametric maps, namely kurtosis fractional anisotropy (kFA), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK), were evaluated at 64 white matter (WM) and gray matter (GM) regions of interest (ROIs) in the whole brain and correlated with the psychometric hepatic encephalopathy score (PHES). Results The MHE group showed a decrease in kFA and AK across the whole brain, whereas MK and RK decreased in WM ROIs but increased in several cortical and deep GM ROIs. These alterations were consistent with brain regions involved in cognitive function. Significant moderate to strong correlations (–0.52 to –0.66; 0.56) between RK, MK and kFA kurtosis metrics and PHES were observed. Conclusion DKI parameters show extensive microstructural brain abnormalities in MHE with minor correlation between the severity of tissue damage and psychometric scores.

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