Quantitative magnetic resonance imaging of brain atrophy in a mouse model of Niemann-Pick type C disease

In vivo magnetic resonance imaging (MRI) was used to investigate regional and global brain atrophy in the neurodegenerative Niemann Pick Type C1 (NPC1) disease mouse model. Imaging experiments were conducted with the most commonly studied mouse model of NPC1 disease at early and late disease states. High-resolution in vivo images were acquired at early and late stages of the disease and analyzed with atlas-based registration to obtain measurements of twenty brain region volumes. A two-way ANOVA analysis indicated eighteen of these regions were different due to genotype and thirteen showed a significant interaction with age and genotype. The ability to measure in vivo neurodegeneration evidenced by brain atrophy adds to the ability to monitor disease progression and treatment response in the mouse model.NIH NIBIB [R01EB000343]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Example 9 week WT mouse images illustrating processing steps for volumetry analysis.

<p>Orthogonal views of the example T2-weighted in vivo dataset are shown in panel <i>a</i>. The images after semi-automated segmentation to remove signal from non-brain material are shown in panel <i>b</i>. The bias field estimate due to surface coil sensitivity inhomogeneity obtained from N4ITK software is shown in panel <i>c</i>. Panel <i>d</i> is the processed 3D dataset ready for image registration and analysis.</p

Change in the volume of mouse brain regions with age.

<p>Percent change in whole brain and brain region volumes between 3 and 9 months of age for WT (blue) and <i>Npc1</i>^-/- (red) mice. Errors bars indicate the standard deviation of the percent change. Significant effects of genotype (*) and age (*) and significant interaction between age and genotype (*) were determined from a two-way ANOVA and p<0.05 after Holm-Bonferroni correction.</p

Example anatomical MRI images of mice at early and late timepoints.

<p>Example high resolution T2-weighted in vivo images of <i>Npc1</i>^-/- (a-c, g-i) and WT (d-f, j-l) mice at 3 weeks (a-f) and 9 weeks (g-l) of age. At three weeks of age there are only slight differences between in the brains of <i>Npc1</i>^-/- and WT mice, but can be seen in the white matter regions of the brain. These differences become more pronounced at 9 weeks of age. The arrow in panel j points to the region of the corpus callosum and external capsule in a WT mouse, which demonstrates a dark band of intensity compared to the surrounding gray matter. This is reversed in the <i>Npc1</i>^-/- mouse. The cerebellum is circled in panel <i>k</i>, which is visibly reduced in size in the <i>Npc1</i>^-/- mouse at 9 weeks. The arrow in panel <i>l</i> indicates the bright signal of the CSF in the lateral ventricles, which are increased in size in the <i>Npc1</i>^-/- mouse at 9 weeks.</p

Brain region volume^*, effects and interactions in 3 and 9 week old Npc1^-/- and control mice.

<p>Brain region volume^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178179#t001fn001" target="_blank">*</a>}, effects and interactions in 3 and 9 week old Npc1^-/- and control mice.</p

A Comparison of Iron Oxide Particles and Silica Particles for Tracking Organ Recellularization

Reseeding of decellularized organ scaffolds with a patient's own cells has promise for eliminating graft versus host disease. This study investigated whether ultrasound imaging or magnetic resonance imaging (MRI) can track the reseeding of murine liver scaffolds with silica-labeled or iron-labeled liver hepatocytes. Mesoporous silica particles were created using the Stober method, loaded with Alexa Flour 647 fluorophore, and conjugated with protamine sulfate, glutamine, and glycine. Fluorescent iron oxide particles were obtained from a commercial source. Liver cells from donor mice were loaded with the silica particles or iron oxide particles. Donor livers were decellularized and reperfused with silica-labeled or iron-labeled cells. The reseeded livers were longitudinally analyzed with ultrasound imaging and MRI. Liver biopsies were imaged with confocal microscopy and scanning electron microscopy. Ultrasound imaging had a detection limit of 0.28 mg/mL, while MRI had a lower detection limit of 0.08 mg/mL based on particle weight. The silica-loaded cells proliferated at a slower rate compared to iron-loaded cells. Ultrasound imaging, MRI, and confocal microscopy underestimated cell numbers relative to scanning electron microscopy. Ultrasound imaging had the greatest underestimation due to coarse resolution compared to the other imaging modalities. Despite this underestimation, both ultrasound imaging and MRI successfully tracked the longitudinal recellularization of liver scaffolds.US Military AcademyOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Age-Related Regional Network Covariance of Magnetic Resonance Imaging Gray Matter in the Rat

Healthy human aging has been associated with brain atrophy in prefrontal and selective temporal regions, but reductions in other brain areas have been observed. We previously found regional covariance patterns of gray matter with magnetic resonance imaging (MRI) in healthy humans and rhesus macaques, using multivariate network Scaled Subprofile Model (SSM) analysis and voxel-based morphometry (VBM), supporting aging effects including in prefrontal and temporal cortices. This approach has yet to be applied to neuroimaging in rodent models of aging. We investigated 7.0T MRI gray matter covariance in 10 young and 10 aged adult male Fischer 344 rats to identify, using SSM VBM, the age-related regional network gray matter covariance pattern in the rodent. SSM VBM identified a regional pattern that distinguished young from aged rats, characterized by reductions in prefrontal, temporal association/perirhinal, and cerebellar areas with relative increases in somatosensory, thalamic, midbrain, and hippocampal regions. Greater expression of the age-related MRI gray matter pattern was associated with poorer spatial learning in the age groups combined. Aging in the rat is characterized by a regional network pattern of gray matter reductions corresponding to aging effects previously observed in humans and non-human primates. SSM MRI network analyses can advance translational aging neuroscience research, extending from human to small animal models, with potential for evaluating mechanisms and interventions for cognitive aging.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]