Significant Microstructural Alterations Research Articles

Biophysical modeling and diffusion kurtosis imaging reveal microstructural alterations in normal-appearing white-matter regions of the brain in obstructive sleep apnea.

Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA. Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers. OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort. Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.

Unveiling the performance of graphene nanofiber additives in gypsum plasters: A solid vs liquid perspective

Graphene nanofibers (GNFs) are promising additives for the gypsum industry. However, their impact in different forms and configurations remains unexplored. This study delves into the effects of different types of GNF additives on the properties of gypsum plasters. Findings reveal that high-surface-area (HS) GNFs and liquid low-surface-area (LS) GNFs induced significant microstructural alterations. While rheology remained unaffected, GNFs accelerated gypsum hydration, leading to fast setting. Furthermore, these GNFs promoted the appearance of anhydrite, resulting in a porous matrix with shorter crystals and poor bonding. These microstructural changes significantly reduced both flexural and compressive strength, with losses of approximately 25%. The incorporation of surfactants further exacerbated these negative effects by limiting crystal formation and growth. Consequently, liquid GNF additives exhibited the lowest performance and durability attributes. While GNFs may impart improved thermal performance to gypsum components, their implementation can also lead to significant reductions in mechanical strength and durability. More research is required to develop additives that are more compatible and do not compromise the performance of the resulting components. Building practices interested in implementing graphene-based materials should focus on powdered additives with very low specific surface area (<100 m2/g) to minimize toxicity and negative impacts on strength and durability.

Enhancing mechanical properties of selective-laser-melting TiN/AISI 420 composites through Taguchi GRA and PCA multi-response optimization

The enhancement of mechanical properties in martensitic AISI 420 stainless steel is realized through the incorporation of TiN ceramic particles using the selective laser melting (SLM) method. This study introduces an innovative hybrid mixing method designed to uniformly disperse TiN within the AISI 420 matrix, ensuring the absence of agglomerations and contaminations in the feedstock for the SLM process. Employing a combined approach involving the Taguchi method, Grey Relational Analysis, and Principle Component Analysis, optimal processing parameters and TiN content are identified, encompassing a laser power of 350 W, laser speed of 370 mm/s, hatch distance of 0.07 mm, layer thickness of 0.05 mm, and one percent by weight of TiN particles. The optimized SLM sample showcases exceptional characteristics with a hardness of 743 ± 20 HV, tensile strength of 1822 ± 21 MPa, and a modulus of toughness of 99.7 ± 3.0 J/m3, surpassing existing results. Introducing TiN particles into the AISI 420 matrix with suitable SLM processing parameters induces significant microstructural alterations, reinforcing the matrix and elevating the mechanical properties. These results mark a substantial advancement in metal matrix composite materials by applying cutting-edge manufacturing techniques.

Corpus callosum damage in PSP and unsteady PD patients: A multimodal MRI study

IntroductionPostural instability (PI) is a common disabling symptom in Parkinson’s disease (PD) patients, but the brain alterations underlying this sign are not fully understood yet. This study aimed to investigate the association between PI and callosal damage in PD and progressive supranuclear palsy (PSP) patients, using multimodal MR imaging. MethodsOne-hundred and two PD patients stratified according to the presence/absence of PI (PD-steady N=58; PD-unsteady N=44), 69 PSP patients, and 38 healthy controls (HC) underwent structural and diffusion 3T brain MRI. Thickness, fractional anisotropy (FA) and mean diffusivity (MD) were calculated over 50 equidistant points covering the whole midsagittal profile of the corpus callosum (CC) and compared among groups. Associations between imaging metrics and postural instability score were investigated using linear regression. ResultsBoth PSP and PD-unsteady patient groups showed CC involvement in comparison with HC, while no difference was found between PD-steady patients and controls. The CC damage was more severe and widespread in PSP than in PD patients. The CC genu was the regions most damaged in PD-unsteady patients compared with PD-steady patients, showing significant microstructural alterations of MD and FA metrics. Linear regression analysis pointed at the MD in the CC genu as the main contributor to PI among the considered MRI metrics. ConclusionThis study identified callosal microstructural alterations associated with PI in unsteady PD and PSP patients, which provide new insights on PI pathophysiology and might serve as imaging biomarkers for assessing postural instability progression and treatment response.

A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age

Traumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during childhood can produce long-lasting modifications within the brain is still debated. We aimed to assess the consequences of a single juvenile mild TBI (jmTBI) at 12 months post-injury in a mouse model. Non-invasive diffusion tensor imaging (DTI) revealed significant microstructural alterations in the hippocampus and the in the substantia innominata/nucleus basalis (SI/NB), structures known to be involved in spatial learning and memory. DTI changes paralled neuronal loss, increased astrocytic AQP4 and microglial activation in the hippocampus. In contrast, decreased astrocytic AQP4 expression and microglia activation were observed in SI/NB. Spatial learning and memory were impaired and correlated with alterations in DTI-derived derived fractional ansiotropy (FA) and axial diffusivity (AD). This study found that a single juvenile mild TBI leads to significant region-specific DTI microstructural alterations, distant from the site of impact, that correlated with cognitive discriminative novel object testing and spatial memory impairments at 12 months after a single concussive injury. Our findings suggest that exposure to jmTBI leads to a chronic abnormality, which confirms the need for continued monitoring of symptoms and the development of long-term treatment strategies to intervene in children with concussions.

Longitudinal evaluation of neuroinflammation and oxidative stress in a mouse model of Alzheimer disease using positron emission tomography.

BackgroundValidation of new biomarkers of Alzheimer disease (AD) is crucial for the successful development and implementation of treatment strategies. Additional to traditional AT(N) biomarkers, neuroinflammation biomarkers, such as translocator protein (TSPO) and cystine/glutamine antiporter system (xc-), could be considered when assessing AD progression. Herein, we report the longitudinal investigation of [18F]DPA-714 and [18F]FSPG for their ability to detect TSPO and xc- biomarkers, respectively, in the 5xFAD mouse model for AD.MethodsExpression of TSPO and xc- system was assessed longitudinally (2–12 months of age) on 5xFAD mice and their respective controls by positron emission tomography (PET) imaging using radioligands [18F]DPA-714 and [18F]FSPG. In parallel, in the same mice, amyloid-β plaque deposition was assessed with the amyloid PET radiotracer [18F]florbetaben. In vivo findings were correlated to ex vivo immunofluorescence staining of TSPO and xc- in microglia/macrophages and astrocytes on brain slices. Physiological changes of the brain tissue were assessed by magnetic resonance imaging (MRI) in 12-month-old mice.ResultsPET studies showed a significant increase in the uptake of [18F]DPA-714 and [18F]FSPG in the cortex, hippocampus, and thalamus in 5xFAD but not in WT mice over time. The results correlate with Aβ plaque deposition. Ex vivo staining confirmed higher TSPO overexpression in both, microglia/macrophages and astrocytes, and overexpression of xc- in non-glial cells of 5xFAD mice. Additionally, the results show that Aβ plaques were surrounded by microglia/macrophages overexpressing TSPO. MRI studies showed significant tissue shrinkage and microstructural alterations in 5xFAD mice compared to controls.ConclusionsTSPO and xc- overexpression can be assessed by [18F]DPA-714 and [18F]FSPG, respectively, and correlate with the level of Aβ plaque deposition obtained with a PET amyloid tracer. These results position the two tracers as promising imaging tools for the evaluation of disease progression.Graphical abstractLongitudinal in vivo study in the 5xFAD mouse model shows that TSPO and oxidative stress assessment through [18F]DPA-714 and [18F]FSPG-PET imaging, respectively, could serve as a potential tool for the evaluation of Alzheimer disease progression. Supplementary InformationThe online version contains supplementary material available at 10.1186/s13195-022-01016-5.

Hippocampal-subfield microstructures and their relation to plasma biomarkers in Alzheimer's disease.

Hippocampal subfields exhibit differential vulnerabilities to Alzheimer's disease-associated pathology including abnormal accumulation of amyloid-β deposition and neurofibrillary tangles. These pathological processes extensively impact on the structural and functional interconnectivities of the subfields and may explain the association between hippocampal dysfunction and cognitive deficits. In this study, we investigated the degree of alterations in the microstructure of hippocampal subfields across the clinical continuum of Alzheimer's disease. We applied a grey matter-specific multi-compartment diffusion model (Cortical-Neurite orientation dispersion and density imaging) to understand the differential effects of Alzheimer's disease pathology on the hippocampal subfield microstructure. A total of 119 participants were included in this cross-sectional study. Participants were stratified into three categories, cognitively normal (n = 47), mild cognitive impairment (n = 52), and Alzheimer's disease (n = 19). Diffusion MRI, plasma biomarkers and neuropsychological test scores were used to determine the association between the microstructural integrity and Alzheimer's disease-associated molecular indicators and cognition. For Alzheimer's disease-related plasma biomarkers, we studied amyloid-β, total tau and neurofilament light; for Alzheimer's disease-related neuropsychological tests, we included the Trail Making Test, Rey Auditory Verbal Learning Test, Digit Span and Montreal Cognitive Assessment. Comparisons between cognitively normal subjects and those with mild cognitive impairment showed significant microstructural alterations in the hippocampal cornu ammonis (CA) 4 and dentate gyrus region, whereas CA 1-3 was the most sensitive region for the later stages in the Alzheimer's disease clinical continuum. Among imaging metrics for microstructures, the volume fraction of isotropic diffusion for interstitial free water demonstrated the largest effect size in between-group comparisons. Regarding the plasma biomarkers, neurofilament light appeared to be the most sensitive biomarker for associations with microstructural imaging findings in CA4-dentate gyrus. CA 1-3 was the subfield which had stronger correlations between cognitive performance and microstructural metrics. Particularly, poor performance on the Rey Auditory Verbal Learning Test and Montreal Cognitive Assessment was associated with decreased intracellular volume fraction. Overall, our findings support the value of tissue-specific microstructural imaging for providing pathologically relevant information manifesting in the plasma biomarkers and neuropsychological outcomes across various stages of Alzheimer's disease.

Unraveling the MRI-Based Microstructural Signatures Behind Primary Progressive and Relapsing-Remitting Multiple Sclerosis Phenotypes.

BackgroundThe mechanisms driving primary progressive and relapsing–remitting multiple sclerosis (PPMS/RRMS) phenotypes are unknown. Magnetic resonance imaging (MRI) studies support the involvement of gray matter (GM) in the degeneration, highlighting its damage as an early feature of both phenotypes. However, the role of GM microstructure is unclear, calling for new methods for its decryption.PurposeTo investigate the morphometric and microstructural GM differences between PPMS and RRMS to characterize GM tissue degeneration using MRI.Study TypeProspective cross‐sectional study.SubjectsForty‐five PPMS (26 females) and 45 RRMS (32 females) patients.Field Strength/Sequence3T scanner. Three‐dimensional (3D) fast field echo T1‐weighted (T1‐w), 3D turbo spin echo (TSE) T2‐w, 3D TSE fluid‐attenuated inversion recovery, and spin echo‐echo planar imaging diffusion MRI (dMRI).AssessmentT1‐w and dMRI data were employed for providing information about morphometric and microstructural features, respectively. For dMRI, both diffusion tensor imaging and 3D simple harmonics oscillator based reconstruction and estimation models were used for feature extraction from a predefined set of regions. A support vector machine (SVM) was used to perform patients' classification relying on all these measures.Statistical TestsDifferences between MS phenotypes were investigated using the analysis of covariance and statistical tests (P < 0.05 was considered statistically significant).ResultsAll the dMRI indices showed significant microstructural alterations between the considered MS phenotypes, for example, the mode and the median of the return to the plane probability in the hippocampus. Conversely, thalamic volume was the only morphometric feature significantly different between the two MS groups. Ten of the 12 features retained by the selection process as discriminative across the two MS groups regarded the hippocampus. The SVM classifier using these selected features reached an accuracy of 70% and a precision of 69%.Data ConclusionWe provided evidence in support of the ability of dMRI to discriminate between PPMS and RRMS, as well as highlight the central role of the hippocampus.Level of Evidence2Technical Efficacy Stage3

Increased extracellular free-water in adult male rats following in utero exposure to maternal immune activation

BackgroundIn previous work, we applied novel in vivo imaging methods to reveal that white matter pathology in patients with first-episode psychosis (FEP) is mainly characterized by excessive extracellular free-water, and to a lesser extent by cellular processes, such as demyelination. Here, we apply a back-translational approach to evaluate whether or not a rodent model of maternal immune activation (MIA) induces patterns of white matter pathology that we observed in patients with FEP. To this end, we examined free-water and tissue-specific white matter alterations in rats born to mothers exposed to the viral mimic polyriboinosinic-polyribocytidylic acid (Poly-I:C) in pregnancy, which is widely used to produce alterations relevant to schizophrenia and is characterized by a robust neuroinflammatory response. MethodPregnant dams were injected on gestational day 15 with the viral mimic Poly-I:C (4 mg/kg) or saline. Diffusion-weighted magnetic resonance images were acquired from 17 male offspring (9 Poly-I:C and 8 saline) on postnatal day 90, after the emergence of brain structural and behavioral abnormalities. The free-water fraction (FW) and tissue-specific fractional anisotropy (FAT), as well as conventional fractional anisotropy (FA) were computed across voxels traversing a white matter skeleton. Voxel-wise and whole-brain averaged white matter were tested for significant microstructural alterations in immune-challenged, relative to saline-exposed offspring. ResultsCompared to saline-exposed offspring, those exposed to maternal Poly-I:C displayed increased extracellular FW averaged across voxels comprising a white matter skeleton (t(15) = 2.74; p = 0.01). Voxel-wise analysis ascribed these changes to white matter within the corpus callosum, external capsule and the striatum. In contrast, no significant between-group differences emerged for FAT or for conventional FA, measured across average and voxel-wise white matter. ConclusionWe identified excess FW across frontal white matter fibers of rats exposed to prenatal immune activation, analogous to our “bedside” observation in FEP patients. Findings from this initial experiment promote use of the MIA model to examine pathological pathways underlying FW alterations observed in patients with schizophrenia. Establishing these mechanisms has important implications for clinical studies, as free-water imaging reflects a feasible biomarker that has so far yielded consistent findings in the early stages of schizophrenia.

Mapping the impact of exposure to maternal immune activation on juvenile Wistar rat brain macro- and microstructure during early post-natal development.

Maternal immune activation is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of maternal immune activation effects across the lifespan. In this context, we recently reported the effects of polyriboinosinic-polyribocytidylic acid–induced maternal immune activation at gestational day 15, immediately prior to birth, at gestational day 21 and again at post-natal day 21, providing a systematic assessment of plasma interleukin 6, body temperature and weight alterations in pregnant rats and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offsprings at these time points. Here, we sought to complement and extend these data by characterising in more detail the mesoscale impact of gestational polyriboinosinic-polyribocytidylic acid exposure at gestational day 15 on the neuroanatomy of the juvenile (post-natal day 21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational polyriboinosinic-polyribocytidylic acid exposure (n = 10) relative to saline controls (n = 10) at this time-point. Specifically, we found an increase in the relative volume of the diagonal domain in polyriboinosinic-polyribocytidylic acid offspring (p < 0.01 uncorrected), which just failed to pass stringent multiple comparisons correction (actual q = 0.07). No statistically significant microstructural alterations were detectable using diffusion tensor imaging. Further studies are required to map the proximal effects of maternal immune activation on the developing rodent brain from foetal to early post-natal life and confirm our findings herein.

Effect of Residual Stresses on Microstructural Evolution Due to Rolling Contact Fatigue

Rolling contact fatigue (RCF) induces a complex subsurface stress state, which produces significant microstructural alterations within bearing steels. A novel modeling approach is presented in this paper, which investigates the effects of microstructural deterioration, phase transformations, and residual stress (RS) formation occurring within bearing steels subject to RCF. The continuum damage mechanics approach was implemented to capture microstructural decay. State and dissipation functions corresponding to the damage mechanics process were used via an energy criterion to predict the phase transformations of retained austenite (RA). Experimental measurements for RA decomposition and corresponding RS were combined to produce a function providing RS formation as a function of RA decomposition and stress history within the material. Microstructural decay, phase transformations, and internal stresses were implemented within a two-dimensional (2D) finite element analysis (FEA) line contact model to investigate variation in microstructural alterations due to RSs present within the material. In order to verify the model developed for this investigation, initial simulations were performed implementing conditions of previously published experimental work and directly comparing to observed RA decomposition and RS formation in 52100 steel deep groove ball bearings. The finite element model developed was then used to implement various RS profiles commonly observed due to manufacturing processes such as laser-shot peening and carburizing. It was found that some RS profiles are beneficial in altering RA decomposition patterns and increasing life while others proved less advantageous.

Effects of SYN1Q555X mutation on cortical gray matter microstructure.

A new Q555X mutation on the SYN1 gene was recently found in several members of a family segregating dyslexia, epilepsy, and autism spectrum disorder. To describe the effects of this mutation on cortical gray matter microstructure, we performed a surface-based group study using novel diffusion and quantitative multiparametric imaging on 13 SYN1Q555X mutation carriers and 13 age- and sex-matched controls. Specifically, diffusion kurtosis imaging (DKI) and neurite orientation and dispersion and density imaging (NODDI) were used to analyze multi-shell diffusion data and obtain parametric maps sensitive to tissue structure, while quantitative metrics sensitive to tissue composition (T1, T2* and relative proton density [PD]) were obtained from a multi-echo variable flip angle FLASH acquisition. Results showed significant microstructural alterations in several regions usually involved in oral and written language as well as dyslexia. The most significant changes in these regions were lowered mean diffusivity and increased fractional anisotropy. This study is, to our knowledge, the first to successfully use diffusion imaging and multiparametric mapping to detect cortical anomalies in a group of subjects with a well-defined genotype linked to language impairments, epilepsy and autism spectrum disorder (ASD).

Assessment of Corneal Changes Associated with Topical Antiglaucoma Therapy Using in vivo Confocal Microscopy

Purpose: Ocular surface disease (OSD) is highly prevalent in eyes treated with chronic, topical antiglaucoma (A/G) therapy. The purpose of this study was to utilize in vivo confocal microscopy (IVCM) to evaluate the corneal morphology, including characteristics of corneal epithelial cells, presence of epithelial dendritic cells (DCs), and characteristics of subbasal nerve plexus, of eyes under topical A/G therapy versus normal eyes. Methods: Central corneal images were prospectively captured from 30 eyes of 16 patients under topical A/G therapy (>6 months) and 20 normal control eyes, using IVCM (HRT 3 RCM, Heidelberg, Germany). Demographic data were collected, as well as information on the types and duration of A/G therapy. In addition, OSD index (OSDI) score, tear film breakup time, Schirmer 1 test results, density of epithelial wing cells (WCs) and basal cells (BCs), subbasal nerve features (density, tortuosity, and reflectivity), and presence of DCs were all assessed and recorded by trained Doheny Image Reading Center graders. Results: IVCM findings of 30 glaucomatous eyes and 20 normal control eyes were analyzed. The mean OSDI score was 8.72 in controls and 32.06 in patients under A/G therapy (p = 0.002). Nerve fiber density, nerve fiber reflectivity, and BC density were all decreased in the A/G group (1,789.07 ± 785.70 μm/frame, 2.79 ± 0.83, 6,457.67 ± 692.55 cells/mm², respectively) as compared to controls (2,815.981 ± 563.77 μm/frame, 3.52 ± 0.50, 7,854.13 ± 1,073.69 cells/mm², respectively) (p < 0.05), whereas the decrease in WC density was statistically nonsignificant (p = 0.5). Nerve tortuosity and DC density were both significantly greater in the A/G eyes (3.00 ± 0.57, 71.24 ± 61.74 cells/mm², respectively) compared to controls (2.10 ± 0.42, 34.08 ± 11.70 cells/mm², respectively) (p < 0.05). Tear film breakup time and Schirmer 1 test results were significantly lower in the A/G group as compared to controls (p < 0.001). Conclusions: Using IVCM, our study identified significant microstructural alterations in the corneas of eyes treated with topical A/G therapy. In addition, our study also revealed that glaucoma patients treated with topical A/G therapy report significantly higher OSDI scores compared to controls. Thus, IVCM may be a useful tool in providing structural parameters to correlate with the functional OSDI assessments in the evaluation of ocular surface toxicity associated with topical A/G therapy.

Differential microstructural alterations in rat cerebral cortex in a model of chronic mild stress depression.

Chronic mild stress leads to depression in many cases and is linked to several debilitating diseases including mental disorders. Recently, neuronal tracing techniques, stereology, and immunohistochemistry have revealed persistent and significant microstructural alterations in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which form an interconnected system known as the stress circuit. Most studies have focused only on this circuit, however, some studies indicate that manipulation of sensory and motor systems may impact genesis and therapy of mood disorders and therefore these areas should not be neglected in the study of brain microstructure alterations in response to stress and depression. For this reason, we explore the microstructural alterations in different cortical regions in a chronic mild stress model of depression. The study employs ex-vivo diffusion MRI (d-MRI) to assess cortical microstructure in stressed (anhedonic and resilient) and control animals. MRI is followed by immunohistochemistry to substantiate the d-MRI findings. We find significantly lower extracellular diffusivity in auditory cortex (AC) of stress groups and a significantly higher fractional anisotropy in the resilient group. Neurite density was not found to be significantly higher in any cortical ROIs in the stress group compared to control, although axonal density is higher in the stress groups. We also report significant thinning of motor cortex (MC) in both stress groups. This is in agreement with recent clinical and preclinical studies on depression and similar disorders where significant microstructural and metabolic alterations were found in AC and MC. Our findings provide further evidence that the AC and MC are sensitive towards stress exposure and may extend our understanding of the microstructural effects of stress beyond the stress circuit of the brain. Progress in this field may provide new avenues of research to help in diagnosis and treatment intervention for depression and related disorders.

Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1H MR spectroscopy (1H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, WL and WT). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or oxidative stress. The significantly increased WL in the AM and HP may indicate hypertrophy of AM and reduced volume of HP. Such metabolic and microstructural alterations could be useful in disease diagnosis and follow-up treatment intervention in depression and similar disorders.

Mapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing.

GPR88 is an orphan G-protein coupled receptor originally characterized as a striatal-enriched transcript and is a potential target for neuropsychiatric disorders. At present, gene knockout studies in the mouse have essentially focused on striatal-related functions and a comprehensive knowledge of GPR88 protein distribution and function in the brain is still lacking. Here, we first created Gpr88-Venus knock-in mice expressing a functional fluorescent receptor to fine-map GPR88 localization in the brain. The receptor protein was detected in neuronal soma, fibers and primary cilia depending on the brain region, and remarkably, whole-brain mapping revealed a yet unreported layer-4 cortical lamination pattern specifically in sensory processing areas. The unique GPR88 barrel pattern in L4 of the somatosensory cortex appeared 3 days after birth and persisted into adulthood, suggesting a potential function for GPR88 in sensory integration. We next examined Gpr88 knockout mice for cortical structure and behavioral responses in sensory tasks. Magnetic resonance imaging of live mice revealed abnormally high fractional anisotropy, predominant in somatosensory cortex and caudate putamen, indicating significant microstructural alterations in these GPR88-enriched areas. Further, behavioral analysis showed delayed responses in somatosensory-, visual- and olfactory-dependent tasks, demonstrating a role for GPR88 in the integration rather than perception of sensory stimuli. In conclusion, our data show for the first time a prominent role for GPR88 in multisensory processing. Because sensory integration is disrupted in many psychiatric diseases, our study definitely positions GPR88 as a target to treat mental disorders perhaps via activity on cortical sensory networks.

Microstructure of the Midbrain and Cervical Spinal Cord in Idiopathic Restless Legs Syndrome: A Diffusion Tensor Imaging Study.

Diffusion tensor imaging (DTI) allows the study of white matter microstructure in the central nervous system. The aim of this study was to examine the DTI metrics of the cervical spinal cord and the brainstem up to the midbrain in patients with idiopathic restless legs (RLS) compared to matched healthy controls. DTI analysis of the cervical spinal cord and the brainstem up into the midbrain was performed in 25 patients with idiopathic RLS and 25 matched healthy controls. Data analysis in the brain was performed by voxelwise comparison of fractional anisotropy (FA) maps at group level. Cervical spinal cord data analysis was performed by slicewise analysis of averaged FA values in axial slices along the spinal cord. Voxelwise comparison of FA maps in the brainstem showed significant microstructural alterations in two clusters in the midbrain bilaterally. Slicewise comparison of the FA maps in the cervical spinal cord showed a trend for lower FA values at the level of the second and third vertebra area in the patient sample. The imaging data suggest that significant alterations in the midbrain in RLS can be visualized by DTI and might correlate to a macroscopically subtle process with changes of the tissue microstructure in the corresponding tracts. An additional area of interest is regionally clustered in the upper cervical spinal cord with a tendency toward altered diffusion metrics. These results might be addressed by further studies, e.g., at higher magnetic field strengths.

Characterization and shelf life of β-carotene loaded solid lipid microparticles produced with stearic acid and sunflower oil

Solid lipid microparticles were tested as microencapsulation systems for protecting β-carotene from degradation. Blends of long-chain (C18) solid lipids (70% stearic acid) and sunflower oil (30%) were used to produce lipid microparticles encapsulating the carotenoid. Polysorbate 80 (4%) was employed to stabilize the stearic acid microparticles. The concentration of β-carotene was monitored using spectrophotometry, the particle size distribution was measured by laser diffraction, the crystal structure was determined by wide angle X-ray diffraction (WAXD), and the thermal behaviour was characterized by differential scanning calorimetry (DSC) over a period of seven months. All of the systems had an average particle size smaller than 5 µm. To avoid β-carotene oxidation, α-tocopherol was added to the formulations and its action as an oxygen trap was crucial for the antioxidant effect. For stearic-acid microparticles with a-tocopherol, more than 90% of the initial amount of β-carotene was preserved after seven months under refrigerated storage (7-10°C) in the dark. Significant microstructural alterations were detected using WAXD and DSC only in the stearic acid microparticles without alpha-tocopherol. These results seemed promising and suggested that the blends of long-chain solid lipids and liquid lipids were suitable for the production of stable solid lipid microparticles.

Mechanical, Electrical and Microstructural Properties of Cement-Based Materials in Conditions of Stray Current Flow

This investigation presents a comparative study on mechanical properties, electrical resistivity and microstructure of mortar under DC current, compared to mortar in rest (no current) conditions. Monitoring was performed from 24h after casting until 84 days of cement hydration. A current density level of 10 mA/m2 was chosen as a simulation regime. It was found that the DC current exerts microstructural changes in the bulk mortar matrix and thereby affects electrical properties and mechanical performance. Whereas the latter were slightly influenced, the former were modified to a more significant extent; the current flow was found to cause initial densification of the bulk matrix at earlier stages (until 14 days of age), whereas coarsening of the material was observed after 56 and until 84 days of cement hydration. Additionally, numerical simulation of the stray current distribution is performed, meant to serve as a basis for further elaborated modelling of the level of current density that could exert significant microstructural alterations in a bulk cement-based matrix.

Microstructural changes in the hippocampus and posterior cingulate in mild cognitive impairment and Alzheimer’s disease: a diffusion tensor imaging study

Diffusion tensor imaging (DTI) is a sensitive MRI technique in the detection of white matter degeneration. We sought to demonstrate microstructural changes in normal controls, patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) and to determine which DTI parameters could be a reliable tool for the early diagnosis of AD. In total, 90 participants (35 normal, 20 aMCI, 35 AD) were recruited. We included early AD patients with clinical dementia rating scores of 0.5 and 1. The fractional anisotropy and mean diffusivity values, DTI parameter, were measured with the regions of interest method in the bilateral hippocampal body and posterior cingulate. Clinical history, neurological examination, and neuropsychological assessments were conducted. The DTI parameters in the bilateral hippocampus and posterior cingulate in aMCI and AD were different from those in normal controls. No difference was found in DTI parameters of the posterior cingulate between aMCI and AD. However, hippocampal DTI parameters were different between aMCI and AD. Cognitive summary measures were significantly correlated with DTI parameters, especially FA values in the hippocampus. The DTI analysis technique demonstrated significant microstructural alterations in the hippocampus and posterior cingulate already in prodromal stage of AD. DTI parameters in the hippocampus may be a more sensitive method to determine microstructural changes in early AD states and more correlated with cognition than DTI parameters in the posterior cingulate.