High b-value Diffusion MRI for Characterizing White Matter Damage

Diffusion magnetic resonance imaging has been widely used to study white matter diseases due to the ubiquity and its non-invasive nature. Amyotrophic lateral sclerosis (ALS), characterized with white matter track damage, is a progressive motor neuron disease in brain and spinal cord with an unknown etiology. Most of diffusion MRI studies focused on altered water diffusion properties in white mater. Nevertheless, the white matter damage might be reflected by the changes of myelin diffusion behaviors that are highly critical, but rarely studied. This thesis aims to characterize white matter damage in a murine model of ALS by analyzing the diffusion properties of myelin using ultra high b-value diffusion MRI. All MRI measurements were performed using a 9.4 T MRI scanner (Agilent, Santa Clara, CA). Stimulated echo acquisition mode sequence was employed with diffusion gradients applied in parallel and perpendicular to the long axis of spinal cord of symptomatic G93A-SOD1 and wild type animal groups respectively. Fast spin echo sequence was employed for anatomical images (T2 weighted). Three diffusion models, bi-exponential, continuous-time random walk (CTRW) model and bi-component model combining CTRW and mono-exponential models were used to analyze the data. Axonal fiber morphology and integrity of the spinal cords were validated by histological analysis. We found differences of signal intensities at lumbar level between diseased and control animals and diffusion-weighted signal decay varied with the diffusion weighting direction relative to spinal nerve fiber orientation on high b-value diffusion-weighted images. Additionally, we found the bi-component model demonstrated the best fit among the three models. In summary, this work has demonstrated the feasibility of diffusion MRI at high b values to evaluate spinal cord alterations in a symptomatic mouse model of ALS. In addition, high b-value diffusion MRI has potential to evaluate spinal cord alterations in other diseases associated with white matter damage

Multicomponent Diffusion-Weighted MRI: Revealing Microenvironment Changes in Degenerative Spinal Cord

Diffusion-weighted Imaging (DWI) is a well-established magnetic resonance imaging technique commonly used in studying neurodegeneration in the brain and spinal cord. The DWI techniques have predominantly focused on brain investigations and the studies on spinal cord share technical similarities with those conducted on the brain. However, there are notable differences between the brain and spinal cord. The brain exhibits greater isotropy, whereas the spinal cord demonstrates more anisotropy. Consequently, specific DWI techniques that take advantage of the spinal cord's anisotropic nature may outperform the commonly used techniques designed for isotropic objects. Unfortunately, research on the application of these specific DWI techniques in the spinal cord is limited. Hence, the aim of this dissertation is to explore this new regime and expand the knowledge of a specialized DWI technique, ultra-high b-value DWI, for the classification of healthy and Amyotrophic Lateral Sclerosis (ALS) affected mouse spinal cords. To address the knowledge gap surrounding the utilization of ultra-high b-value techniques, a systematic study incorporating simulation, phantom, ex vivo, and in vivo investigations was conducted. The dissertation begins with simulation and phantom studies, which validated the feasibility of employing regularized (Non-negative Least Squares) NNLS methods for decomposing DWI data. Subsequently, the ex vivo study demonstrated the potential to encode diffusion contrast from ultra-high b-values onto DW images. Moreover, the ex vivo data was analyzed using the well-established L2-norm regularized NNLS method in Myelin Water Imaging, successfully capturing microenvironmental changes in mouse spinal cords caused by ALS. However, the L2-norm regularization exhibited an over-smoothing effect in the results. To address this issue, a novel L1-norm regularized NNLS method was introduced and applied to analyze the same ex vivo datasets. Additionally, the decomposition nature of NNLS methods facilitated another study that explored the impact of low b-values on DW signals. Drawing upon the knowledge and insights gained from the preceding studies, DWI protocols incorporating ultra-high b-values were developed for in vivo mouse spinal cord imaging. The results obtained using the novel L1-norm regularized NNLS method on the in vivo data unveiled new imaging indices for classifying ventral roots in wild-type and ALS-affected animals at the pre-symptomatic stage (P75) and early symptomatic stage (P90). Furthermore, lower signal intensities were observed in the ventral roots of ALS-affected spinal cords, and the results obtained from the proposed L1-norm regularized NNLS method affirmed a shift towards higher diffusion coefficient ranges in weight distributions. These findings may potentially describe changes in the local environment as the disease progresses

High b-value Diffusion MRI for Characterizing White Matter Damage

Diffusion magnetic resonance imaging has been widely used to study white matter diseases due to the ubiquity and its non-invasive nature. Amyotrophic lateral sclerosis (ALS), characterized with white matter track damage, is a progressive motor neuron disease in brain and spinal cord with an unknown etiology. Most of diffusion MRI studies focused on altered water diffusion properties in white mater. Nevertheless, the white matter damage might be reflected by the changes of myelin diffusion behaviors that are highly critical, but rarely studied. This thesis aims to characterize white matter damage in a murine model of ALS by analyzing the diffusion properties of myelin using ultra high b-value diffusion MRI. All MRI measurements were performed using a 9.4 T MRI scanner (Agilent, Santa Clara, CA). Stimulated echo acquisition mode sequence was employed with diffusion gradients applied in parallel and perpendicular to the long axis of spinal cord of symptomatic G93A-SOD1 and wild type animal groups respectively. Fast spin echo sequence was employed for anatomical images (T2 weighted). Three diffusion models, bi-exponential, continuous-time random walk (CTRW) model and bi-component model combining CTRW and mono-exponential models were used to analyze the data. Axonal fiber morphology and integrity of the spinal cords were validated by histological analysis. We found differences of signal intensities at lumbar level between diseased and control animals and diffusion-weighted signal decay varied with the diffusion weighting direction relative to spinal nerve fiber orientation on high b-value diffusion-weighted images. Additionally, we found the bi-component model demonstrated the best fit among the three models. In summary, this work has demonstrated the feasibility of diffusion MRI at high b values to evaluate spinal cord alterations in a symptomatic mouse model of ALS. In addition, high b-value diffusion MRI has potential to evaluate spinal cord alterations in other diseases associated with white matter damage

The initial lengths (mm) of fish in the four replicates.

<p>Both the means and the standard deviations are included.</p><p>The initial lengths (mm) of fish in the four replicates.</p

Data_Sheet_1_Analysis of burnout and its influencing factors among prison police.PDF

BackgroundBurnout among prison police is an occupational health issue in the field of public health. Although burnout has been a hot issue for decades, there has not been a focus on the specific group of prison police. This study explores the burnout status and its influencing factors among prison police.MethodsThe Maslach Burnout Questionnaire—General Survey (MBI-GS) was used to conduct a questionnaire survey among 1,024 prison police.ResultsIt indicates that emotional exhaustion, negative detachment, and self-efficacy were the most significant dimensions of the burnout among prison police officers. The results of multiple linear regression analysis showed that gender (−0.201, P = 8.8958E-11 ConclusionsBurnout among prison officers can be reduced through preferential treatment of prison police, sound organizational mechanisms, and self-improvement of prison police.</p

Telomere length through time.

<p>The relative telomere length is reported for larvae (age 1 D), females and males from the early breeding period, age 150 days (Early F and Early M respectively), and females and males from late breeding period, 200 days (Late F and Late M respectively). The left panel indicates results for brain tissue and the right panel indicates telomere lengths for muscle. The red line for each box indicates the mean, box edges indicate 25% and 75% percentile, and the whiskers show outlier outside +/-2.7 standard deviation.</p

A GMC Oxidoreductase Homologue Is Required for Acetylation of Glycopeptidolipid in <i>Mycobacterium smegmatis</i>

The <i>Mycobacterium tuberculosis Rv3409c</i> gene is required for modulation of the Toll-like receptor 2 (TLR-2) signaling response in infected macrophages. Although each is annotated as encoding a cholesterol oxidase, neither <i>Rv3409c</i> nor its ortholog <i>MSMEG1604</i> is required for the metabolism of cholesterol in mycobacteria. Here we report that a unique lipid, L1334, accumulates in a MSMEG1604 transposon mutant in the <i>Mycobacterium smegmatis</i> cell envelope. L1334 is a polar glycopeptidolipid that is hyperrhamnosylated and in which the 6-deoxytalose moiety is not acetylated. The alteration of L1334 acetylation is consistent with a reduced level of interference with TLR-2 signaling in mutant infected macrophages

The regression statistics of RTL and RTL length residuals on dry gonad mass separated by tissue and gender.

<p>The significant values are in bold and SE stands for standard error. The significance test for p<0.001 means that p is within the interval [0, 0.001].</p><p>The regression statistics of RTL and RTL length residuals on dry gonad mass separated by tissue and gender.</p

The regression statistics of RTL on final length and dry gonad mass separated by tissue and gender.

<p>The significant values are in bold and SE stands for standard error.</p><p>The regression statistics of RTL on final length and dry gonad mass separated by tissue and gender.</p

Correlation in RTL between brain and muscle tissue samples.

<p>Although differences between tissues were tested using a paired t-test, a linear regression is shown here for visualization.</p