Diffusion kurtosis imaging: An efficient tool for evaluating age-related changes in rat brains.

PURPOSE: To evaluate and determine age-related changes in rat brains by studying the diffusion kurtosis imaging results among different age groups of rats. METHODS: Sprague-Dawley (SD) rats underwent conventional magnetic resonance imaging (MRI) and diffusion Kurtosis Imaging (DKI). Two diffusion values of mean kurtosis (MK) and kurtosis (K⊥ ) were measured and analyzed based on laterality, brain regions and age groups. The MK and K⊥ data were plotted against different age groups. RESULTS: No laterality was found for the MK or K⊥ values in the cerebral cortex (CT), external capsule (EC), or caudate putamen (CPu) regions. In contrast, significant changes in these values were observed among different age groups. Changes of the MK and K⊥ values were significant in both hemispheres in the EC, the CT, and the CPu brain regions. The changes in the MK and K⊥ values showed a parabolic relationship with ages in all the brain regions. CONCLUSION: No laterality in the MK and K⊥ values was observed for the EC, CT, or CPu regions of the rat brain. Significant changes in MK and K⊥ values were both observed among different age groups, thus suggesting diffusion kurtosis imaging as an efficient tool for studying brain aging in rats.

Proton magnetic resonance spectroscopy reveals significant decline in the contents of N-acetylaspartylglutamate in the hippocampus of aged healthy subjects.

INTRODUCTION: To characterize the contents of choline (Cho), creatine (Cr) and N-acetylaspartylglutamate (NAA) in the hippocampus of healthy volunteers, we investigated the contents and their correlationship with age, gender and laterality. MATERIAL AND METHODS: Volunteers were grouped into a young, a middle and an old age. The Cho, Cr and NAA contents were determined with proton magnetic resonance spectroscopy (1H-MRS), and the correlationship was analyzed with Pearson correlation. RESULTS: The concentration of NAA in the bilateral hippocampi was markedly lower in the old than in the young and the middle (LSD test, all p < 0.025). Furthermore, NAA/Cr in the bilateral hippocampi head (left: 1.10 ±0.40 vs. 1.54 ±0.49 or 1.43 ±0.49; right: 1.04 ±0.42 vs. 1.35 ±0.40 or 1.30 ±0.42), region 1 of the bilateral hippocampal body (left: 1.24 ±0.53 vs. 1.58 ±0.58 or 1.35 ±0.44; right: 1.30 ±0.43 vs. 1.54 ±0.51 or 1.35 ±0.51) and region 2 of the left hippocampal body (1.21 ±0.32 vs. 1.46 ±0.36 or 1.36 ±0.44) and the left hippocampal tail (1.11 ±0.40 vs. 1.36 ±0.47 or 1.15 ±0.32) was significantly higher in the old than in the young and the middle, respectively (all p < 0.026). The NAA content in the bilateral hippocampal head, body and tail negatively correlated with age. Moreover, the NAA, Cho and Cr contents in the hippocampal body and the tail were higher in the right than the left. CONCLUSIONS: The NAA content of the hippocampal head, body and tail were significantly decreased in the old compared with younger persons, and it negatively correlates with age. The NAA, Cho and Cr contents exhibit laterality in the hippocampal body and tail.

A voxel-based morphometric study of age- and sex-related changes in white matter volume in the normal aging brain.

OBJECTIVE: To carry out a cross-sectional study of 187 cognitively normal Chinese adults using the voxel-based morphometry (VBM) approach to delineate age-related changes in the white matter volume of regions of interest in the brain and further analyze their correlation with age. MATERIALS AND METHODS: A total of 187 cognitively normal adults were divided into the young, middle, and old age-groups. Conventional magnetic resonance imaging was performed with the Achieva 3.0 T system. Structural images were processed using VBM8 and statistical parametric mapping 8. Regions of interest were obtained by WFU PickAtlas, and all realigned images were spatially normalized. RESULTS: Females showed significantly greater total white matter volume than males (t=2.36, P=0.0096, false-discovery rate [FDR] corrected). VBM demonstrated statistically significant age-related differences in white matter volume between the young age-group and the middle age-group (P<0.05, FDR corrected) and between the middle age-group and the old age-group (P<0.05, FDR corrected). No interaction was found between age and sex on white matter volume (P<0.05, FDR corrected). Logistic regression analysis revealed nonlinear correlation between total white matter volume and age (R (2)=0.124, P<0.001). White matter volume gradually increased before 40 years of age, peaked around 50 years of age, and rapidly declined after 60 years of age. CONCLUSION: Significant age-related differences are present in white matter volume across multiple brain regions during aging. The VBM approach may help differentiate underlying normal neurobiological aging changes of specific brain regions from neurodegenerative impairments.

A Cross-Sectional Voxel-Based Morphometric Study of Age- and Sex-Related Changes in Gray Matter Volume in the Normal Aging Brain.

OBJECTIVE: The aim of the study was to carry out a cross-sectional study of 124 cognitively normal Chinese adults using the voxel-based morphometry approach to delineate age-related changes in the gray matter volume of regions of interest (ROI) in the brain and further analyze their correlation with age. METHODS: One hundred twenty-four cognitively normal adults were divided into the young age group, the middle age group, and the old age group. Conventional magnetic resonance imaging was performed with the Achieva 3.0 T system. Structural images were processed using VBM8 and SPM8. Regions of interest were obtained by WFU PickAtlas and all realigned images were spatially normalized. RESULTS: Females showed significantly greater total gray matter volume than males (t = 4.81, P = 0.0000, false discovery rate corrected). Compared with young subjects, old-aged subjects showed extensive reduction in gray matter volumes in all ROIs examined except the occipital lobe. In young- and middle-aged subjects, female and male subjects showed significant difference in the right middle temporal gyrus, right superior temporal gyrus, left angular gyrus, right middle occipital lobe, left middle cingulate gyrus, and the pars triangularis of the right inferior frontal gyrus, suggesting an interaction between age and sex (P < 0.001, uncorrected). Logistic regression analysis revealed linear negative correlation between the total gray matter volume and age (R = 0.529, P < 0.001). CONCLUSIONS: Significant age-related differences are present in gray matter volume across multiple brain regions during aging. The VPM approach may provide an emerging paradigm in the normal aging brain that may help differentiate underlying normal neurobiological aging changes of specific brain regions from neurodegenerative impairments.

MRI localization of the subthalamic nucleus in normal adults and its relation with age.

The subthalamic nucleus regulates motor and neurocognitive functions. Because of its small size and close proximity to other small subcortical structures, it has been a challenge to localize and visualize it using MRI. Here, we sought to define the optimal MRI scan method and visualization plane for locating the subthalamic nucleus on MRI images and to further delineate the geometric dimensions of the subthalamic nucleus and their correlation with age, laterality, and sex. Healthy volunteers received axial, sagittal, and coronal T2_3D_DRIVE CLEAR, coronal T1-WI, coronal T2FLAIR, coronal T2, and coronal SWI sequence. The coronal T2-3D-DRIVE CLEAR images were compared with the Schaltenbrand-Wahren Atlas for Stereotaxy of the Human Brain for localizing the subthalamic nucleus. The best visualization plane with the largest sectional area and the most distinct outline was obtained and region of interest was delineated manually on the basis of the contours of the bilateral subthalamic nuclei in T2-WI images. T2-3D-DRIVE CLEAR in the coronal view showed optimal visualization of the subthalamic nucleus and indicated that the subthalamic nucleus showed three morphological types: the double convex lens type (172, 64%), the ram's horn type (62, 23%), and the willow leaf type (34, 13%). There were no statistically significant differences because of laterality, sex, and age in the sectional area, and maximal long and short diameter of the subthalamic nucleus. On the basis of our results, the current study has shown that T2-3D-DRIVE CLEAR in the coronal view provides optimal visualization of the subthalamic nucleus, which shows three distinct morphological types on MRI images, and there is no statistically significant difference in the geometric dimensions of the subthalamic nucleus because of laterality, sex, and age in normal individuals.

Study of functional connectivity in patients with sensorineural hearing loss by using resting-state fMRI.

OBJECTIVE: To determine functional connectivity of the default mode network in patients with sensorineural hearing loss (SNHL) in resting state. METHODS: The posterior cingulate cortex was selected as a seed for assessment of functional connectivity of the activated brain areas in resting state by using a seed-based correlation analysis of the resting state functional magnetic resonance imaging (fMRI) data. RESULTS: The fMRI results demonstrated that, the healthy volunteers and the patients with NSHL shared certain activated brain areas with positive functional connectivity with region of interest (ROI). However, the healthy volunteers also had positive functional connectivity with ROI in bilateral middle temporal gyrus, left anterior cingulate cortex, right inferior parietal lobule and left medial superior frontal gyrus. While the patients with SNHL did with bilateral inferior parietal lobule, left medial superior frontal gyrus, right supramarginal gyrus, and left middle temporal gyrus. Compared to controls, patients with SNHL showed increased functional connectivity in the right posterior frontal lobe, right precentral gyrus, right supramarginal gyrus and left posterior cingulate cortex, and had decreased functional connectivity in the left lingual gyrus, right cuneus lobe and right superior frontal gyrus. CONCLUSION: The posterior cingulate cortex, precuneus lobe, medial frontal gyrus, anterior cingulate cortex, temporal lobe, angular gyrus and inferior parietal lobule constitute a default mode of network in normal resting status. And patients with SNHL have abnormal functional connectivity of default mode network and cortical reorganisation in resting status.

Alternative Fas-mediated cell death pathway is dependent on the different cleavage patterns of procaspase-8.

It has been reported that mitochondria-independent or mitochondria-dependent (type I/II) Fas signaling pathways in leukemia cells depend on the amount of active caspase-8. However, Bid molecules, which could not be cleaved in type I cells, could be effectively cleaved by recombinant active caspase-8 in vitro. The cleavage of recombinant Bid by recombinant active caspase-8 could be blocked by anti-p10 and anti-p18 specific antibodies. Fas receptors could be similarly internalized into cytoplasm in type I and type II cells. Interestingly, p10 subunit of active caspase-8 could be detected in both type I and II cells, while p18 subunit of active caspase-8 could be detected only in type II cells but not in type I cells. These results demonstrated that p18 subunit was necessary for Bid cleavage and the mitochondria pathway might be dependent on the release of p18 subunit from active caspase-8.

Intracellular localization of protein C inhibitor (PCI) and urinary plasminogen activator in renal tubular epithelial cells from humans and human PCI gene transgenic mice.

Urinary plasminogen activator (uPA) is a serine protease that plays important roles in various extracellular proteolytic processes. In humans, protein C inhibitor (PCI) is known to regulate the activity of the serine proteases involved in blood coagulation, wound healing, and tumor metastasis, whereas PCI is not present in murine plasma or tissues other than the reproductive tissues. The large amount of uPA-PCI complexes found in human urine suggests that these complexes are formed in the kidneys. In the present study, we performed immunofluorescence double labeling and electron microscopic immunocytochemistry using renal tissues from humans and human PCI gene transgenic (PCI-TG) mice. In human renal tissues, PCI and uPA colocalized in the cytoplasm of renal proximal tubular epithelial cells (RPTECs), and juxtaposition of PCI and uPA immunoreactive particles was detected in the microvilli and lysosomes in the RPTECs. The intracellular distributions of PCI and uPA in the RPTECs from PCI-TG mice were similar to those observed in human RPTECs. These findings hint at the physiological roles of uPA and PCI in human kidneys, and also suggest that the PCI-TG mice will be useful for evaluating the roles of PCI in human physiological and pathological conditions.