Average FA Research Articles

Absolute purity determination of an organic fluorine pharmaceutical voriconazole via quantitative 19F NMR and method validation

The 19F NMR spectrum has a smaller number of signals than 1H NMR, therefore, quantitative 19F NMR (19F-qNMR) can replace quantitative 1H NMR (1H-qNMR) for the absolute quantitation of organic fluorine-bearing compounds. In this study, we determined the purity of voriconazole (VCZ), an organic fluorine pharmaceutical, using 19F-qNMR, validated the results in multiple laboratories, and compared them with those obtained using an established 1H-qNMR method. 3,5-Bis(trifluoromethyl)benzoic acid (3,5-BTFMBA) was selected as the reference standard for both 19F-qNMR and 1H-qNMR owing to its solubility characteristics and 19F-qNMR and 1H-qNMR chemical shifts.Since VCZ contains three fluorines, the 19F-qNMR spectrum of VCZ showed three major fluorine signals (FA, FB, and FC). 19F-qNMR measurements were performed under three conditions with each 19F signal of VCZ (FA, FB, and FC) and the 19F signal of RS as the center (offset) of each observation. The quantitative values of the three target signals FA, FB, and FC were calculated and were comparable; 99.40 %, 99.66 %, and 99.49 %, respectively.Owing to a difference of up to 8.8 % between the quantitative values of the two signals other than the targeted quantitative signal, the average FA, FB, and FC quantitative values were considered for purity (%). The purity of VCZ determined by 1H- and 19F-qNMR was comparable (99.65±0.29 % and 99.52±0.44 %, respectively), exhibiting variations within an acceptable range. Compared to conventional 1H-qNMR methods, the developed 19F-qNMR method has been proven efficient and highly promising for determining the accurate purity of organic fluorine pharmaceuticals.

Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study

BackgroundSocial anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined. Methods85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables. ResultsA significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: −0.006, 95 % CI: −0.0108 – −0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables. ConclusionsBased on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia.

Posterior white matter integrity and self-reported posterior cortical symptoms using the Colorado Posterior Cortical Questionnaire.

The Colorado Posterior Cortical Questionnaire (CPC-Q) is a self-report, 15-item screening questionnaire for posterior cortical symptoms, including visuospatial and visuoperceptual difficulties. Changes in white matter connectivity may precede obvious gray matter atrophy in neurodegenerative conditions, especially posterior cortical atrophy. Integration of CPC-Q scores and measures of white matter integrity could contribute to earlier detection of posterior cortical syndromes. We investigated the relationships between posterior cortical symptoms as captured by the CPC-Q and diffusion tensor imaging fractional anisotropy (DTI FA) of white matter regions of interest localized to posterior brain regions (posterior thalamic radiations, splenium of corpus callosum, tapetum). Comparisons were also made by diagnostic group [healthy older adult (n = 31), amnestic Alzheimer's disease (AD, n = 18), and posterior cortical atrophy (PCA, n = 9)] and by SENAS battery visuospatial composite score quartile. Exploratory comparisons of all available individual white matter region DTI FA to CPC-Q, as well as comparisons of DTI FA between diagnostic groups and visuospatial quartiles, were also made. CPC-Q score was correlated with the average DTI FA for the averaged posterior white matter regions of interest (r = -0.31, p = 0.02). Posterior thalamic radiation DTI FA was most strongly associated with CPC-Q (r = -0.34, p = 0.01) and visuospatial composite (r = 0.58, p < 0.01) scores and differed between the PCA and AD groups and the lower and higher visuospatial quartiles. The DTI FA of body and splenium of the corpus callosum also demonstrated this pattern but not the DTI FA of the tapetum. The integrity of posterior white matter tracts is associated with scores on the CPC-Q, adding to the validation evidence for this new questionnaire. White matter regions that may be related to posterior cortical symptoms detected by the CPC-Q, and distinct from those affected in amnestic syndromes, include the posterior thalamic radiations and body and splenium of the corpus callosum. These findings are in line with previous neuroimaging studies of PCA and support continued research on white matter in posterior cortical dysfunction.

Rapidly declining body size in an insectivorous bat is associated with increased precipitation and decreased survival.

Reduced food availability is implicated in declines in avian aerial insectivores, but the effect of nutritional stress on mammalian aerial insectivores is unclear. Unlike birds, insectivorous bats provision their young through lactation, which might protect nursing juveniles when prey availability is low but could increase the energetic burden on lactating females. We analyzed a 15-year capture-mark-recapture data set from 5312 individual little brown myotis (Myotis lucifugus) captured at 11 maternity colonies in northwestern Canada, to test the hypothesis that nutritional stress is impacting these mammalian aerial insectivores. We used long-bone (forearm [FA]) length as a proxy for relative access to nutrition during development, and body mass as a proxy for access to nutrition prior to capture. Average FA length and body mass both decreased significantly over the study period in adult females and juveniles, suggesting decreased access to nutrition. Effect sizes were very small, similar to those reported for declining body size in avian aerial insectivores. Declines in juvenile body mass were only observed in individuals captured in late summer when they were foraging independently, supporting our hypothesis that lactation provides some protection to nursing young during periods of nutritional stress. Potential drivers of the decline in bat size include one or both of (1) declining insect (prey) abundance, and (2) declining prey availability. Echolocating insectivorous bats cannot forage effectively during rainfall, which is increasing in our study area. The body mass of captured adult females and juveniles in our study was lower, on average, after periods of high rainfall, and higher after warmer-than-average periods. Finally, survival models revealed a positive association between FA length and survival, suggesting a fitness consequence to declines in body size. Our study area has not yet been impacted by bat white-nose syndrome (WNS), but research elsewhere has suggested that fatter bats are more likely to survive infection. We found evidence for WNS-independent shifts in the body size of little brown myotis, which can inform studies investigating population responses to WNS. More broadly, the cumulative effects of multiple stressors (e.g., disease, nutritional stress, climate change, and other pressures) on mammalian aerial insectivores require urgent attention.

Characterizing the canine and feline optic pathways in vivo with diffusion MRI.

The visual system is known to be vital for cognition and perception in the feline and canine and much behavioral research for these species has used visual stimuli and focused on visual perception. There has been extensive investigations into the visual pathway in cats and dogs via histological and neurobiological methods, however to date, only one study has mapped the canine optic pathway in vivo. Advanced imaging methods such as diffusion MRI (DTI) have been routinely used in human research to study the visual system in vivo. This study applied DTI imaging methods to assess and characterize the optic pathway of feline and canine subjects in vivo. The optic nerve (ON), optic tract (OT), and optic radiation (OR) were successfully delineated for each species and the average volume and FA for each tract is reported. The application of DTI to map the optic pathway for canine and feline subjects provides a healthy baseline for comparison in future studies.

Does stress mess with rodents' heads? Influence of habitat amount and genetic factors in mandible fluctuating asymmetry in South American water rats (Nectomys squamipes, Sigmodontinae) from Brazilian Atlantic rainforest remnants.

Loss of developmental stability can lead to deviations from bilateral symmetry (i.e. Fluctuating Asymmetry ‐ FA), and is thought to be caused by environmental and genetic factors associated with habitat loss and stress. Therefore, levels of FA might be a valuable tool to monitor wild populations if FA serves as an indicator of exposure to stress due to impacts of habitat loss and fragmentation. In studies examining FA and habitat fragmentation, FA levels are often explained by loss of genetic variation, though few studies have addressed FA’s use as indicator of environmental impact. Here, we investigated whether habitat loss, genetic variation, and/or inbreeding affect the developmental instability in Brazilian Atlantic forest populations of a Neotropical water rat (Nectomys squamipes). We sampled individuals from eight sites within Atlantic forest remnants with different amounts of available forest habitat and assessed FA levels with geometric morphometric techniques using adult mandibles. We used observed heterozygosity (Ho) and inbreeding coefficient (Fis), from seven microsatellite markers, as a proxy of genetic variation at individual and population levels. Populations were not significantly different for shape or size FA levels. Furthermore, interindividual variation in both shape and size FA levels and interpopulational differences in size FA levels were best explained by chance. However, habitat amount was negatively associated with both interpopulational variance and average shape FA levels. This association was stronger in populations living in areas with <28% of forest cover, which presented higher variance and higher average FA, suggesting that Nectomys squamipes might have a tolerance threshold to small availability of habitat. Our work is one of the first to use FA to address environmental stress caused by habitat loss in small mammal populations from a Neotropical biome. We suggest that shape FA might serve as a conservation tool to monitor human impact on natural animal populations.

Can white matter lesion burden predict involvement of normal appearing thalami in multiple sclerosis? Study using 3D FLAIR and DTI

BackgroundMultiple sclerosis is a chronic demyelinating disease that affects the white and grey matter. The thalamus is responsible for many neurological functions, and it is liable to damage in multiple sclerosis in the absence of MRI-detectable thalamic lesions. Standardized imaging protocol for multiple sclerosis includes 3D FLAIR sequence that is highly sensitive in detecting white matter lesions. Owing to the thalamic functional importance, we aim in this study to show to what extent the standardized imaging protocol (3D FLAIR) can predict microscopic damage of normal appearing thalami, depending on DTI metrics (ADC and FA) as indicators of the microscopic damage.ResultsWe examined 42 multiple sclerosis patients, 16 males and 26 females, with mean age 29 ± 6 years using 3D FLAIR sequence to delineate the white matter lesions and calculate their total areas and using DTI to calculate the average ADC and FA values of the thalami. Spearman’s correlation coefficient (r) was used to correlate between the white matter lesion burden and the thalamic diffusivity (ADC and FA).Moderate correlation was found between average ADC values of the thalami and the total white matter lesion areas (r = 0.5, p = 0.03).Very weak correlation was found between average FA values of the thalami and the total white matter lesion areas (r = − 0.1, p = 0.6)ConclusionWhite matter lesion burden detected using the highly sensitive 3D FLAIR sequence does not always correlate with the microstructural damage in normal appearing thalami. DTI needs to be added to the examination protocol if damage of normal appearing thalami is of concern.

Comparison Matrix-Associated Stem Cell Transplantation (MAST) with Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC+PBC) in Chondral Lesions at the Ankle - Matched-Patient Analysis

Category:AnkleIntroduction/Purpose:2016, the local government authorities re-categorized MAST, i.e. the included BMAC for impregnation of the matrix, as stem call manufacturing and heterologous transplantation. Consequently, MAST and all other procedures including BMAC were not ‘subject to disclosure’ as before but ‘subject to authorization’. Therefore, the authors´ institution was not authorized to perform MAST after July 16, 2016. The authors´ institution changed the treatment of chondral lesions by replacing BMAC as part of MAST to Peripheral Blood Concentrate (PBC) resulting in AMIC+PBC.The aim of the study was to compare MAST with AMIC+PBC in chondral lesions at the ankle.Methods:In a matched-patient clinical follow-up study, patients with chondral lesion at the ankle that were treated with AMIC+PBC from July 17, 2016 to May 31, 2017, and patients that were treated with MAST from April 1, 2009 to July 15, 2016 were included and compared. Size and location of the chondral lesions and the Visual-Analogue-Scale Foot and Ankle (VAS FA) before treatment and at follow-up were analysed. Bone Marrow Aspirate Concentrate (BMAC) was used for MAST and Peripheral Blood Concentrate (PBC) for AMIC+PBC to impregnate a collagen I/III matrix (Chondro-Gide, Wollhusen, Switzerland) that was fixed into the chondral lesion with fibrin glue.Results:One hundred and twenty-nine patients with 136 chondral lesions were included in both groups. The chondral lesions were located as follows (MAST/AMIC+PBC, n (%)), medial talar shoulder only, 59 (43)/62 (46); lateral talar shoulder only, 44 (32)/42 (31); medial and lateral talar shoulder, 7 (10)/7 (10); tibia, 19 (14)/18 (13). The lesion size was 1.6/1.8cm2 on average and VAS FA was 46.9/45.7 (MAST/AMIC+PBC). For MAST/AMIC+PBC groups, 107 (83%)/105 (81%) with 112/110 previous chondral lesions completed the defined 2-year-follow-up after 24.4/23.8 months on average. VAS FA improved to 82.3/79.8 (MAST/AMIC+PBC). No parameter significantly differed between MAST and AMIC+PBC groups.Conclusion:MAST and AMIC+PBC as part of a complex surgical approach led to improved and high validated outcome scores in 2-year-follow-up. MAST and AMIC+PBC showed similar results. No method related complications were registered.

MR spectroscopy differences between lipomatosis of nerve and neuromuscular choristoma: a potential adjunctive diagnostic tool.

To describe differences between lipomatosis of nerve (LN) and neuromuscular choristoma (NMC) evaluated with MR spectroscopy (MRS). Eight patients were included in this prospective pilot study: three patients with LNs and five with NMCs. Single voxel PRESS MRS of the tumors were acquired with 3T MRI. MRS data were processed with LCModel version 6.3-1J using the internal "lipid-8" basis set. From individual lipid peak and water content measurements, total fatty acid molecules (TFAM), unsaturated fatty acid molecules (UFAM), and glycerol molecules (GM) were computed and analyzed, as well as ratios of UFAM/TFAM, TFAM/GM, and a fatty-acid chain-length index (CLI). The LN group included two men and one woman (average age 58.3years); the NMC group included two men and three women (average age 20.4years). Lipid composition analysis showed that LN had considerably more fat than NMC: TFAM: LN = 15.29 vs NMC = 7.14; UFAM: LN = 4.48 vs NMC = 2.63; GM: LN = 5.20 vs NMC = 1.02. Both tumors had a similar fraction of unsaturated fatty acids: UFAM/TFAM: LN = 0.29 vs NMC = 0.37. LN had the usual number of FA molecules/glycerol molecule, while NMC had considerably more: TFAM/GM: LN = 2.94 vs NMC = 6.98. Finally, average FA chains were longer in NMC: CLI: LN = 17.39 vs NMC = 22.55. Our analysis suggests measurable differences in the amount and composition of lipid in LN and NMC. While a larger, statistically powered study is needed, these initial findings may be helpful to properly diagnose ambiguous cases and thereby avoid surgical intervention such as biopsy.

Comparison Matrix-Associated Stem Cell Transplantation (MAST) with Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC + PBC) in chondral lesions at the ankle—A clinical matched-patient analysis

BackgroundThe aim of the study was to compare Matrix-Associated Stem Cell Transplantation (MAST) with Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC+PBC) in chondral lesions at the ankle. MethodsIn a matched-patient clinical follow-up study, patients with chondral lesion at the ankle that were treated with MAST from April 1, 2009 to July 15, 2016, and patients that were treated with AMIC+PBC from July 17, 2016 to May 31, 2017 were included and compared. Size and location of the chondral lesions and the Visual-Analogue-Scale Foot and Ankle (VAS FA) before treatment and at follow-up were analysed. Bone Marrow Aspirate Concentrate (BMAC) was used for MAST and Peripheral Blood Concentrate (PBC) for AMIC+PBC to impregnate a collagen I/III matrix (Chondro-Gide, Wollhusen, Switzerland) that was fixed into the chondral lesion with fibrin glue. ResultsOne hundred and twenty-nine patients with 136 chondral lesions were included in both groups. The chondral lesions were located as follows (MAST/AMIC+PBC, n (%)), medial talar shoulder only, 59 (43)/62 (46); lateral talar shoulder only, 44 (32)/42 (31); medial and lateral talar shoulder, 7 (10)/7 (10); tibia, 19 (14)/18 (13). The lesion size was 1.6/1.8cm2 on average and VAS FA was 46.9/45.7 (MAST/AMIC+PBC). For MAST/AMIC+PBC groups, 107 (83%)/105 (81%) with 112/110 previous chondral lesions completed the defined 2-year-follow-up after 24.4/23.8 months on average. VAS FA improved to 82.3/79.8 (MAST/AMIC+PBC). No parameter significantly differed between MAST and AMIC+PBC groups. ConclusionsMAST and AMIC+PBC as part of a complex surgical approach led to improved and high validated outcome scores in 2-year-follow-up. MAST and AMIC+PBC showed similar results.

Characterization of the microstructure of the intervertebral disc in patients with chronic low back pain by diffusion kurtosis imaging.

Multivariate analysis of T2-weighted signal, diffusion ADC, and DKI parameters and tractography were used to differentiate chronic non-specific low back pain (CLBP) patients and asymptomatic controls (AC). A total of 30 patients with CLBP and 23 AC underwent diffusion kurtosis imaging (DKI) of lumbar spine with a 3T MRI scanner to get the ADC values and seven parameters of DKI in the nucleus pulposus (NP) of the intervertebral disc. The tractography and the tract-related parameters as other parameters were also generated to indicate the intactness of annulus fibrosus (AF). T2-grades of the discs were also quantified based on an eight-grade degeneration grading system. ADC and T2-grades were compared with DKI parameters for the differentiation of CLBP and AC groups. There was no difference in the T2 grades, ADC value, and multiple parameters in DKI of NP between CLBP and AC groups (P > 0.05). The average FA values in NP in AC group were found significantly higher than in the CLBP group (P < 0.05). The scores for the intactness of AF of the intervertebral discs were significantly different in CLBP and AC groups, with 90% of sensitivity and 70% specificity (P < 0.05). Additionally, there were significantly differences in the length and volume values of the AF in CLBP and AC groups (P < 0.05). DKI is a good noninvasive method, and it might help to differentiate CLBP from AC. Particularly, the continuation of DKI tractography reflects the presence of annulus fibrosus fissures, an important character in the generation of the low back pain. These slides can be retrieved under Electronic Supplementary Material.

Application of a machine learning method to whole brain white matter injury after radiotherapy for nasopharyngeal carcinoma

BackgroundThe purpose/aim of this study was to 1) use magnetic resonance diffusion tensor imaging (DTI), fibre bundle/tract-based spatial statistics (TBSS) and machine learning methods to study changes in the white matter (WM) structure and whole brain WM network in different periods of the nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT), 2) identify the most discriminating WM regions and WM connections as biomarkers of radiation brain injury (RBI), and 3) supplement the understanding of the pathogenesis of RBI, which is useful for early diagnosis in the clinic.MethodsA DTI scan was performed in 77 patients and 67 normal controls. A fractional anisotropy map was generated by DTIFit. TBSS was used to find the region where the FA differed between the case and control groups. Each resulting FA value image is registered with each other to create an average FA value skeleton. Each resultant FA skeleton image was connected to feature vectors, and features with significant differences were extracted and classified using a support vector machine (SVM). Next, brain segmentation was performed on each subject’s DTI image using automated anatomical labeling (AAL), and deterministic white matter fiber bundle tracking was performed to generate symmetrical brain matrix, select the upper triangular component as a classification feature. Two-sample t-test was used to extract the features with significant differences, then classified by SVM. Finally, we adopted a permutation test and ROC curves to evaluate the reliability of the classifier.ResultsFor FA, the accuracy of classification between the 0–6, 6–12 and > 12 months post-RT groups and the control group was 84.5, 83.9 and 74.5%, respectively. In the case groups, the FA with discriminative ability was reduced, mainly in the bilateral cerebellum and bilateral temporal lobe, with prolonged time, the damage was aggravated. For WM connections, the SVM classifier classification recognition rates of the 0–6, 6–12 and > 12 months post-RT groups reached 82.5, 78.4 and 76.3%, respectively. The WM connections with discriminative ability were reduced.ConclusionsRBI is a disease involving whole brain WM network anomalies. These brain discriminating WM regions and WM connection modes can supplement the understanding of RBI and be used as biomarkers for the early clinical diagnosis of RBI.

Fecundity of diploid and triploid Carassius gibelio (Bloch, 1782) females

Fecundity of diploid and triploid Carassius gibelio (Bloch, 1782) females

Petrography, mineral chemistry and shock metamorphism of the Mangui meteorite

The Mangui meteorite, also known as the Xishuangbanna meteorite, fell in Menghai, Xishuangbanna Dai Nationality Autonomous Prefecture, Yunnan Province, China at ~9: 45 pm on June 1, 2018. More than 500 fragments of Mangui were collected a total mass of ~50 kg. The mass of the largest fragment is ~1228 g. Mangui has a black fusion crust, a light gray exposure surface, and contains many black shock melt veins and pockets. In this work, the classification of Mingui and its shock history are investigated by studying its petrology, mineral chemistry, and the nature of its shock assemblages. Mangui is mainly composed of olivine, pyroxene, feldspar, Fe-Ni metal, troilite, chromite, merrillite and apatite, showing typical petrologic features of an ordinary chondrite. Relict chondrules are observed in hand specimens but their boundaries are less clear under FE-SEM. Electron Probe Micro Analysis (EPMA) shows that the chemical compositions of olivine (Fa25.1±0.3 mol%( n =71)), low-Ca pyroxene (Fs21.1±0.3Wo1.5±0.2 mol% ( n =58)) and plagioclase Ab84.1±0.7Or7.3±0.4 mol%( n =49)) in Mangui are relatively homogeneous. The petrographic type of Mangui is classified as type 6 by the coarse grains of secondary plagioclase, the homogeneous compositions of olivine and pyroxene, the recrystallization of matrix and blurry boundaries of relict chondrules. The chemical group of Mangui is L based on the average Fa content of olivine (Fe/(Fe+Mg)×100, atomic percentage, 25.1±0.3, n =71) and the average Fs content of pyroxene (Fe/ (Fe+Mg+Ca)×100, atomic percentage, 21.1±0.3, n =58). Therefore, the Mangui meteorite is classified as an L6 ordinary chondrite. The Mangui parent body experienced strong shock metamorphism with the widespread distribution of shock melt veins with widths up to 600 μm. Shock induced melt pockets were also observed. Micron-sized olivine and pyroxene in the center of the shock melt veins display chemical zonation, suggesting that they recrystallized from the shock induced melt. Plagioclase in the shock melt veins has transformed into maskelynite. Two high pressure polymorphs, jadeite and majorite, occur in the shock melt veins and melt pockets as measured by Raman analysis. Jadeite usually displays granular textures in these assemblages as euhedral to sub-euhedral crystals. Majorite was only found in one jadeite assemblage, occurring as inclusions in outer rim of an assemblage. The co-occurrence of majorite and jadeite indicate shock pressures from 17–20 GPa at temperatures ranging from 1900–2000°C. However, ringwoodite, whitlockite and other high pressure polymorphs have not been identified in the shock melt veins pockets. The occurrences of maskelynite, jadeite and majorite, and widespread distribution of shock melt veins and pockets suggest the shock stage of Mangui as S5. The absence of ringwoodite and tuite probably attribute to slow post-shock cooling rates, suggesting that the Mangui parent body experienced strong shock metamorphism with a subsequent slow post-shock cooling history. TEM and XRD work will be performed to better constrain the formation mechanisms of jadeite and majorite and their P - T - t histories. Furthermore, we aim on modelling the impact conditions on the Mangui parent body such as impact velocity, and parent body-impactor sizes by further study of the high-pressure minerals in shock-melt veins of the Mangui meteorite.

A novel DTI-QA tool: Automated metric extraction exploiting the sphericity of an agar filled phantom

PurposeTo develop a quality assurance (QA) tool (acquisition guidelines and automated processing) for diffusion tensor imaging (DTI) data using a common agar-based phantom used for fMRI QA. The goal is to produce a comprehensive set of automated, sensitive and robust QA metrics. MethodsA readily available agar phantom was scanned with and without parallel imaging reconstruction. Other scanning parameters were matched to the human scans. A central slab made up of either a thick slice or an average of a few slices, was extracted and all processing was performed on that image. The proposed QA relies on the creation of two ROIs for processing: (i) a preset central circular region of interest (ccROI) and (ii) a signal mask for all images in the dataset. The ccROI enables computation of average signal for SNR calculations as well as average FA values. The production of the signal masks enables automated measurements of eddy current and B0 inhomogeneity induced distortions by exploiting the sphericity of the phantom. Also, the signal masks allow automated background localization to assess levels of Nyquist ghosting. ResultsThe proposed DTI-QA was shown to produce eleven metrics which are robust yet sensitive to image quality changes within site and differences across sites. It can be performed in a reasonable amount of scan time (~15min) and the code for automated processing has been made publicly available. ConclusionsA novel DTI-QA tool has been proposed. It has been applied successfully on data from several scanners/platforms. The novelty lies in the exploitation of the sphericity of the phantom for distortion measurements. Other novel contributions are: the computation of an SNR value per gradient direction for the diffusion weighted images (DWIs) and an SNR value per non-DWI, an automated background detection for the Nyquist ghosting measurement and an error metric reflecting the contribution of EPI instability to the eddy current induced shape changes observed for DWIs.

The relationship between fractional anisotropy value and tumor microarchitecture in late-stage rat glioma.

To explore the magnetic resonance diffusion tensor imaging (MR-DTI) features of in the late stage of Wistar rat C6 brain glioma, and the relationship between fractional anisotropy value and tumor microarchitecture. The concentration of more than 1.0×106/10μL glioma cells and complete medium were injected stereotactically into the right caudate nucleus of the experimental group (n=35) and control group (n=10), respectively. Conventional MRI, DTI, and enhanced T1WI scans were Performed using the GE Signa HD×3.0T MRI scanner about 3-4 weeks after implantation for the rats. Postprocessing was done using the DTI specific software Function Tool to gain FA image. Many ROIs were drawn avoiding hemorrhage, necrosis areas in tumor parenchyma, the value of FA was recorded. Each surviving rat brain was examined histologically using HE and immunohistochemical staining for VEGF and CD34. Pearson correlation analysis was used to determine the relationships between FA values and VEGF, MVD, cell density, respectively. A total of 35 tumor-bearing rats were confirmed the tumor formation by the subsequent MRI and pathological examination. The mean FA values of the tumor and the contralateral brain tissue were 0.17±0.03 and 0.31±0.05 respectively, and the difference was statistically significant (t=12.80, P<0.05). The mean FA value of grade III glioma (n=12) was 0.16±0.03, and the average FA value of grade IV glioma (n=23) was about 0.18±0.04. There was no significant difference between the two groups (t=1.92, P>0.05). FA value in the late stage of Wistar rat C6 brain glioma has significant positive correlation to VEGF, MVD, cell density. The correlation coefficients between FA and VEGF, MVD, and cell density were 0.67, 0.65 and 0.71 (P<0.05), respectively. The FA value of rat glioma tumor in the late stage can preoperatively provide an accurate, reliable and noninvasive imaging monitoring method to evaluate the microstructure of glioma (cell density, the extent of angiogenesis, fiber bundle integrity and tumor cell infiltration and so on), predict the biological behavior of the tumor and make out surgical plan.

85. Diffusion Imaging of White Matter Pathways in Schizophrenia: Are Illness-Linked Changes Progressive?

Background: The presence of altered white matter microstructure in disorders involving psychosis is well established, but the nature and developmental course of these changes are not well understood (Peters & Karlsgodt, 2015). It is not clear whether the presence of attenuated frontal white matter anisotropy at any phase of illness indexes a pathophysiological change that occurs only within the prodromal and/or first episode phases, or whether early white matter changes are part of a lifespan trajectory of accelerated white matter degeneration in patients (Schwehm et al., 2016; Wright et al., 2014). It also remains to be determined whether schizophrenia-linked anisotropy changes are the result of axon damage or if they also reflect organizational changes. Methods: Diffusion MRI data were collected in 81 schizophrenia patients (54 First Episode and 27 Chronic), and 65 controls (Mean age = 26, 98 males, N = 146). Tract Based Spatial Statistics (TBSS; Smith et al., 2006) were performed to examine group differences in Fractional Anisotropy (FA; a widely used measure of white matter coherence) on a whole-brain voxel-based level. Average FA was extracted from a whole-brain-derived ROI, and subsequently used to examine whether the association between Age and FA differed as a function of illness. Fiber density (“fixel-based”) analysis was also performed (Raffelt et al., 2016). Fixel-based analysis leverages anatomical and crossing-fiber information to assess whether group differences are likely to be attributable to loss of white matter fiber bundle density or cross-section. Results: Compared to controls, the schizophrenia group displayed a pattern of reduced FA in the bilateral frontal lobes and the corpus callosum (FWE-corrected, P < .05). ROI analysis indicated a lack of significant interaction between Group and Age on FA in whole-brain significant regions (P = .81). Preliminary results from whole-brain analyses of fiber density indicate a trending inverse association between fiber density in the postcentral corpus callosum (FWE-corrected P = .08), but no such trend was evident in the frontal regions identified by TBSS analysis of FA. Conclusion: These results replicate the oft-reported finding that frontal and callosal FA is lower in schizophrenia. Cross-sectional analysis of Age and FA indicates that patients do not display a steeper rate of age-related FA decline compared with controls, suggesting that the group difference in FA manifests before the onset of psychosis, but does not progress across phase of illness. Preliminary assessment of fiber density raises the possibility that axon loss within postcentral callosal fiber bundles may be partly responsible for FA changes in postcentral callosal fibers. The lack of group differences in frontal fiber density supports the notion that schizophrenia-linked FA changes in these white matter regions are unlikely to be due to axon loss, but rather, to organizational changes.

Area-Type Adjustment Factors for Non-CBD Signalised Intersections

In the estimation of saturation flow at signalized intersections using the HCM model, the influence of area-type characteristics on flow is accounted for by the area-type adjustment factor (fa). The recommendation by the manual to use fa=0.9 for CBD-intersections and 1.0 for all others tacitly assumes that the nature of non-CBD areas does not influence flow. This may not hold for many developing country cities and metropolitan areas where the roadside environments associated with non-CBD intersections may be laden with a flurry of activities that impact traffic flow. For signalized intersections in such areas, the HCM-recommended area-type adjustment factor could lead to over-estimation of saturation flow rates if the activities create substantial roadside friction to flow. This study set out to develop area-type adjustment factors for non-CBD signalized intersections located within the Kumasi Metropolis in Ghana, to accurately reflect the impact of roadside character on saturation flow rates. Using field saturation flow data collected at selected signalized intersections in the metropolis, area-type adjustment factors were developed for three distinct roadside friction environments categorised in the study as low/none, medium, and high. Average fa values developed were 0.99 for low/none, 0.98 for medium, and 0.94 for high roadside friction environments. Also, a multiple linear regression model that attempts to relate fa to pedestrian traffic interfering with flow within the environment of the intersection was developed as an alternative procedure for determining site specific area-type adjustment factor. It is recommended to use the fa values developed in this study in the HCM saturation flow model in order to estimate more accurately the saturation flow rates at non-CBD signalized intersections within the Kumasi Metropolis.

Abnormal white matter integrity as a structural endophenotype for bipolar disorder.

Several lines of evidence suggest that bipolar disorder (BD) is associated with white matter (WM) pathology. Investigation of unaffected first-degree relatives of BD patients may help to distinguish structural biomarkers of genetic risk without the confounding effects of burden of illness, medication or clinical state. In the present study, we applied tract-based spatial statistics to study WM changes in patients with BD, unaffected siblings and controls. A total of 27 euthymic patients with BD type I, 20 unaffected siblings of bipolar patients and 29 healthy controls who did not have any current or past diagnosis of Axis I psychiatric disorders were enrolled in the study. Fractional anisotropy (FA) was significantly lower in BD patients than in the control group in the corpus callosum, fornix, bilateral superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, posterior thalamic radiation, cingulum, uncinate fasciculus, superior corona radiata, anterior corona radiata and left external capsule. In region-of-interest (ROI) analyses, we found that both unaffected siblings and bipolar patients had significantly reduced FA in the left posterior thalamic radiation, the left sagittal stratum, and the fornix compared with healthy controls. Average FA for unaffected siblings was intermediate between the healthy controls and bipolar patients within these ROIs. Decreased FA in the fornix, left posterior thalamic radiation and left sagittal stratum in both bipolar patients and unaffected siblings may represent a potential structural endophenotype or a trait-based marker for BD.

Structural integrity and functional connectivity of default mode network underlying the cognitive impairment in Late-onset depression

Objective To determine the association between the functional changes and the structural lesions of the DMN underlying the cognitive impairments in Late-onset depression (LOD). Methods Thirty-two LOD patients and thirty-nine normal controls (NCs) were recruited and underwent resting-state fMRI and DTI scans. Cognition was evaluated with MMSE and a battery of neuropsychological measurements. Seed-based correlation analysis was performed to explore the functional connectivity (FC) of the DMN. Then deterministic tractography between FC-impaired regions were calculated to examine structural connectivity (SC). Tracts connecting FC-impaired regions were selected to count fiber number (FN) and to calculate average FA, AD and RD of all voxels along these fibers. Partial correlation analyses were applied to examine cognitive association of these altered FC and SC, controlling the effects of age and education. Results LOD patients showed decreased FC between PCC/Pcu and dACC as well as the thalamus. Decreased FA and increased RD of these fiber tracks connecting PCC/Pcu with dACC were found in LOD patients, without significant difference in AD and FN. The FC between PCC/Pcu and dACC was positively correlated with the FA of fiber tracks connecting them. The PCC/Pcu-dACC FC and the FA of the fiber tracks between them were both positively correlated with Symbol Digit Modalities Test and Verbal Fluency Test scores which conversely displayed negative association with RD. Conclusions The cognitive impairment in LOD, especially executive speed and semantic memory might be associated with the decreased FC in DMN which probably resulted from the demyelination of the white matter.