Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon Microscopy of Cleared Mouse Brain

Kamagata, Koji; Kerever, Aurélien; Yokosawa, Suguru; Otake, Yosuke; Ochi, Hiroki; Hori, Masaaki; Kamiya, Kazutaka; Tsuruta, Kenji; Tagawa, Kazuhiko; Okazawa, Hitoshi; Aoki, Shigeki; Arikawa‐Hirasawa, Eri

doi:10.2463/mrms.bc.2015-0148

Cited by 11 publications

(13 citation statements)

References 15 publications

(15 reference statements)

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“…Kamagata et al reported that FA was very strongly correlated with neurite density in an area where nerve fiber orientations are unidirectionally aligned, such as the medial lemniscus. 26 In this study, FA showed very strong correlation with neurite density in the anterior commissure and the ventral hippocampal commissure where fiber orientations are well aligned, but did not strongly correlate with neurite density in the caudate putamen. These structures contain crossing fibers, whose evaluation by DTI is limited.…”

Section: Discussioncontrasting

confidence: 51%

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

et al. 2018

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Purpose:Diffusional kurtosis imaging (DKI) enables sensitive measurement of tissue microstructure by quantifying the non-Gaussian diffusion of water. Although DKI is widely applied in many situations, histological correlation with DKI analysis is lacking. The purpose of this study was to determine the relationship between DKI metrics and neurite density measured using confocal microscopy of a cleared mouse brain.Methods:One thy-1 yellow fluorescent protein 16 mouse was deeply anesthetized and perfusion fixation was performed. The brain was carefully dissected out and whole-brain MRI was performed using a 7T animal MRI system. DKI and diffusion tensor imaging (DTI) data were obtained. After the MRI scan, brain sections were prepared and then cleared using aminoalcohols (CUBIC). Confocal microscopy was performed using a two-photon confocal microscope with a laser. Forty-eight ROIs were set on the caudate putamen, seven ROIs on the anterior commissure, and seven ROIs on the ventral hippocampal commissure on the confocal microscopic image and a corresponding MR image. In each ROI, histological neurite density and the metrics of DKI and DTI were calculated. The correlations between diffusion metrics and neurite density were analyzed using Pearson correlation coefficient analysis.Results:Mean kurtosis (MK) (P = 5.2 × 10−9, r = 0.73) and radial kurtosis (P = 2.3 × 10−9, r = 0.74) strongly correlated with neurite density in the caudate putamen. The correlation between fractional anisotropy (FA) and neurite density was moderate (P = 0.0030, r = 0.42). In the anterior commissure and the ventral hippocampal commissure, neurite density and FA are very strongly correlated (P = 1.3 × 10−5, r = 0.90). MK in these areas were very high value and showed no significant correlation (P = 0.48).Conclusion:DKI accurately reflected neurite density in the area with crossing fibers, potentially allowing evaluation of complex microstructures.

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Section: Discussioncontrasting

confidence: 51%

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

et al. 2018

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“…Increases in FA without definite cause have also been reported (11)(12)(13). Kamagata et al have found that the correlation between FA and neurite density is weak in the caudate nucleus and putamen, which contain crossing fibers, in the transparent mouse brain (6). An important feature of NODDI is that the degree of orientation dispersion of axons is quantitatively represented by the ODI.…”

Section: Discussionmentioning

confidence: 96%

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

Sato

Kerever

Kamagata

et al. 2017

Acta Radiologica Open

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BackgroundNeurite 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.PurposeTo confirm the concordance of NODDI with histology in terms of density and orientation dispersion of neurites of the brain.Material and MethodsWhole 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.ResultsThe 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.ConclusionNODDI 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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“…Moreover, in vivo UHF-MRI diffusion studies have a critical advantage for longitudinal studies acquired with high spatial resolution [ 46 ]. From the medical perspective, using DTI to gain an understanding of the ultrastructural changes occurring during the early stage of ALS may improve the detection and treatment of this disease at earlier stages [ 10 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice

Gatto

Amin

Deyoung

et al. 2018

Transl Neurodegener

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BackgroundAmyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice.MethodsThe spinal cords from presymptomatic and symptomatic mice (80 to 120 days of age) were scanned (ex-vivo) using diffusion-weighted MRI. The fractional anisotropy (FA), axial (AD) and radial (RD) diffusivities were calculated for axial slices from the thoracic, cervical and lumbar regions of the spinal cords. The diffusion parameters were compared with fluorescence microscopy and membrane cellular markers from the same tissue regions.ResultsAt early stages of the disease (day 80) in the lumbar region, we found, a 19% decrease in FA, a 9% decrease in AD and a 35% increase in RD. Similar changes were observed in cervical and thoracic spinal cord regions. Differences between control and ALS mice groups at the symptomatic stages (day 120) were larger. Quantitative fluorescence microscopy at 80 days, demonstrated a 22% reduction in axonal area and a 22% increase in axonal density. Tractography and quantitative connectome analyses measured by edge weights showed a 52% decrease in the lumbar regions of the spinal cords of this ALS mice group. A significant increase in ADC (23.3%) in the ALS mice group was related to an increase in aquaporin markers.ConclusionsThese findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS.

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Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon Microscopy of Cleared Mouse Brain

Cited by 11 publications

References 15 publications

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

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

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

Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice

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