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Purpose We investigated fractional anisotropy (FA) and radial diffusivity (RD) in a canine model of mucopolysaccharidosis (MPS). We hypothesized that canines affected with MPS would exhibit decreased FA and increased RD values when compared to unaffected canines, a trend that has been previously described in humans with white matter diseases. Methods Four unaffected canines and two canines with MPS were euthanized at 18 weeks of age. Their brains were imaged using high-resolution diffusion tensor imaging (DTI) on a 7T small-animal magnetic resonance imaging system. One hundred regions of interest (ROIs) were placed in each of four white matter regions: anterior and posterior regions of the internal capsule (AIC and PIC, respectively) and anterior and posterior regions of the centrum semiovale (ACS and PCS, respectively). For each specimen, average FA and RD values and associated 95% confidence intervals were calculated from 100 ROIs for each brain region. Results For each brain region, the FA values in MPS brains were consistently lower than in unaffected dogs, and the RD values in MPS dogs were consistently higher, supporting our hypothesis. The confidence intervals for affected and unaffected canines did not overlap in any brain region. Conclusion FA and RD values followed the predicted trend in canines affected with MPS, a trend that has been described in humans with lysosomal storage and dysmyelinating diseases. These findings suggest that the canine model parallels MPS in humans, and further indicates that quantitative DTI analysis of such animals may be suitable for future study of disease progression and therapeutic response in MPS. [ABSTRACT FROM AUTHOR]

The goal of this study was to apply image registration-based automated segmentation methods to measure diffusion tensor imaging (DTI) metrics within the canine brain. Specifically, we hypothesized that this method could measure DTI metrics within the canine brain with greater reproducibility than with hand-drawn region of interest (ROI) methods.We performed high-resolution post-mortem DTI imaging on two canine brains on a 7 T MR scanner. We designated the two brains as brain 1 and brain 2. We measured DTI metrics within the corpus callosum of brain 1 using a hand-drawn ROI method and an automated segmentation method in which ROIs from brain 2 were transformed into the space of brain 1. We repeated both methods in order to measure their reliability.Mean differences between the two sets of hand-drawn ROIs ranged from 4% to 10%. Mean differences between the hand-drawn ROIs and the automated ROIs were less than 3%. The mean differences between the first and second automated ROIs were all less than 0.25%.Our findings indicate that the image registration-based automated segmentation method was clearly the more reproducible method. These results provide the groundwork for using image registration-based automated segmentation methods to measure DTI metrics within the canine brain. Such methods will facilitate the study of white matter pathology in canine models of neurologic disease. [ABSTRACT FROM AUTHOR]

The relationship between superior longitudinal fasciculus microstructural integrity and neuropsychological functions were examined in 49 healthy children (range: 5-17 years) using diffusion tensor imaging. Seven major cognitive domains (intelligence, fine-motor, attention, language, visual-spatial, memory, executive function) were assessed. Data analyses used correlational methods. After adjusting for age and gender, fractional anisotropy and axial diffusivity values in the superior longitudinal fasciculus were positively correlated with executive functions of set shifting, whereas left superior longitudinal fasciculus fractional anisotropy values correlated with attention and language. Apparent diffusion coefficient values in the left superior longitudinal fasciculus negatively correlated with inhibitory control. In the left arcuate fasciculus, fractional anisotropy correlated with IQ and attention, whereas radial diffusivity values negatively correlated with IQ, fine-motor skills, and expressive language. Findings from this study provide an examination of the relationship between superior longitudinal fasciculus integrity and children’s neuropsychological abilities that can be useful in monitoring pediatric neurologic diseases. [ABSTRACT FROM AUTHOR]

Although accumulated evidence supports the concept of endosomal signaling of receptor tyrosine kinases, most results are generated from studies of epidermal growth factor receptor (EGFR). It is not clear whether the concept of endosomal signaling could be generally applied to the other receptor tyrosine kinases. For example, platelet-derived growth factor receptor (PDGFR) is very similar to EGFR in terms of both signaling and trafficking; however, little is known about the endosomal signaling of PDGFR. In this research, we applied the same approaches from our recent studies regarding EGFR endosomal signaling to investigate the endosomal signaling of PDGFR. We showed in this communication that we are able to establish a system that allows the specific activation of endosome-associated PDGFR without the activation of the plasma membrane-associated PDGFR and without disrupting the overall endocytosis pathway. By using this system, we showed that endosomal activation of PDGFR recruits various signaling proteins including Grb2, SHC, phospholipase C-γ1, and the p85α subunit of phosphatidylinositol 3-kinase into endosomes and forms signaling complexes with PDGFR. We also showed that endosomal PDGFR signaling is sufficient to activate the major signaling pathways implicated in cell proliferation and survival. Moreover, we demonstrate that endosomal PDGFR signaling is sufficient to generate physiological output including cell proliferation and cell survival. [ABSTRACT FROM AUTHOR]

Objective: We set out to determine functional white matter (WM) connections passing through the canine corpus callosum; these WM connections would be useful for subsequent studies of canine brains that serve as models for human WM pathway disease. Based on prior studies, we anticipated that the anterior corpus callosum would send projections to the anterior cerebral cortex whereas progressively posterior segments would send projections to more posterior cortex., Materials and Methods: A postmortem canine brain was imaged using a 7-T MRI system producing 100-μm-isotropic-resolution diffusion-tensor imaging analyzed by tractography. Using regions of interest (ROIs) within cortical locations, which were confirmed by a Nissl stain that identified distinct cortical architecture, we successfully identified six important WM pathways. We also compared fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity, and axial diffusivity in tracts passing through the genu and splenium., Results: Callosal fibers were organized on the basis of cortical destination (e.g., fibers from the genu project to the frontal cortex). Histologic results identified the motor cortex on the basis of cytoarchitectonic criteria that allowed placement of ROIs to discriminate between frontal and parietal lobes. We also identified cytoarchitecture typical of the orbital frontal, anterior frontal, and occipital regions and placed ROIs accordingly. FA, ADC, radial diffusivity, and axial diffusivity values were all higher in posterior corpus callosum fiber tracts., Conclusion: Using six cortical ROIs, we identified six major WM tracts that reflect major functional divisions of the cerebral hemispheres, and we derived quantitative values that can be used for study of canine models of human WM pathologic states.