Reduction In FA Research Articles

Sex-Specific Distributed White Matter Microarchitectural Alterations in Preadolescent Youths With Anxiety Disorders: A Mega-Analytic Study.

Anxiety disorders are among the most common psychiatric disorders in youths and emerge during childhood. This is also a period of rapid white matter (WM) development, which is critical for efficient neuronal communication. Previous work in preadolescent children with anxiety disorders demonstrated anxiety disorder-related reductions in WM microstructural integrity (fractional anisotropy [FA]) in the uncinate fasciculus (UF), the major WM tract facilitating prefrontal cortical-limbic structural connectivity. Importantly, this association was found only in boys with anxiety disorders. To confirm this finding and more comprehensively understand WM changes in childhood anxiety, this mega-analytic study characterizes WM alterations related to anxiety disorders and sex in the largest sample of preadolescent children to date. Diffusion tensor imaging data from published studies of preadolescent children with anxiety disorders and healthy volunteers (ages 8-12) (N=198) were combined with a new data set (N=97) for a total sample of 165 children with anxiety disorders and 132 healthy volunteers. Children with anxiety disorders met DSM-5 criteria for current generalized, separation, and/or social anxiety disorder. Analyses of tractography and voxel-wise data assessed between-group differences (anxiety disorder vs. healthy volunteer), effects of sex, and their interaction. Tract-based and voxel-wise analyses confirmed a significant reduction in UF FA in boys but not girls with anxiety disorders. Results also demonstrated other significant widespread anxiety disorder-related WM alterations specifically in boys, including in multiple commissural, association, projection, and brainstem regions. In addition to confirming male-specific anxiety disorder-related reductions in UF FA, the results demonstrate that anxiety disorders in boys and not girls are associated with broadly distributed WM alterations across the brain. These findings support further studies focused on understanding the extent to which WM alterations in boys with anxiety disorders are involved in pathophysiological processes that mediate anxiety disorders. The findings also suggest the possibility that WM microarchitecture could serve as a novel treatment target for childhood anxiety disorders.

Psychological factors and brain magnetic resonance imaging metrics associated with fatigue in persons with multiple sclerosis

BackgroundBesides demographics and clinical factors, psychological variables and brain-tissue changes have been associated with fatigue in persons with multiple sclerosis (pwMS). Identifying predictors of fatigue could help to improve therapeutic approaches for pwMS.Therefore, we investigated predictors of fatigue using a multifactorial approach. Methods136 pwMS and 49 normal controls (NC) underwent clinical, neuropsychological, and magnetic resonance imaging examinations. We assessed fatigue using the “Fatigue Scale for Motor and Cognitive Functions”, yielding a total, motor, and cognitive fatigue score. We further analyzed global and subcortical brain volumes, white matter lesions and microstructural changes (examining fractional anisotropy; FA) along the cortico striatal thalamo cortical (CSTC) loop. Potential demographic, clinical, psychological, and magnetic resonance imaging predictors of total, motor, and cognitive fatigue were explored using multifactorial linear regression models. Results53% of pwMS and 20% of NC demonstrated fatigue. Besides demographics and clinical data, total fatigue in pwMS was predicted by higher levels of depression and reduced microstructural tissue integrity in the CSTC loop (adjusted R2 = 0.52, p < 0.001). More specifically, motor fatigue was predicted by lower education, female sex, higher physical disability, higher levels of depression, and self-efficacy (adjusted R2 = 0.54, p < 0.001). Cognitive fatigue was also predicted by higher levels of depression and lower self-efficacy, but in addition by FA reductions in the CSTC loop (adjusted R2 = 0.45, p < 0.001). ConclusionsOur results indicate that depression and self-efficacy strongly predict fatigue in MS. Incremental variance in total and cognitive fatigue was explained by microstructural changes along the CSTC loop, beyond demographics, clinical, and psychological variables.

Potential Role of MR Diffusion Tensor Imaging of the Spinal Cord in Early Detection of Cervical Spondylotic Myelopathy and Assessment of Its Severity

Background Cervical spondylotic myelopathy is the most common cause of spinal dysfunction in adults. Recent studies have shown a potential role for diffusion tensor imaging as a novel method for early detection of cervical cord myelopathy as compared with conventional MR sequences. Aim of the Work To evaluate the role of MR diffusion tensor imaging in the early detection of cervical spondylotic myelopathic changes in comparison to conventional MRI sequences to determine best clinical management and outcome for the patients. Patients and Methods Our study is a prospective study that included patients from August 2021 to December 2021. The study included 20 patients with clinical symptoms of cervical spondylotic myelopathy, referred to the Radiology department, Ain Shams University Hospitals for MRI cervical study. Results Our results showed a highly significant reduction of FA values and highly significant increase of ADC values of the cord opposite to the level of the most affected disc (P value &amp;lt;0.001 and 0.002 respectively). We also found that the magnitude of FA reduction and ADC increase correlated positively with the severity of disc affection, with the highest drop in FA values and increase in ADC values found to be in patients with established spinal cord hyperintensity on T2WI. Conclusion Diffusion tensor imaging could be used in early detection of cervical cord myelopathy before the appearance of altered cord intensity on conventional MRI sequences and in assessment of its severity.

White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study.

To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.

Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: A neurite orientation dispersion and density imaging study.

To investigate microstructural impairments of corticospinal tracts (CSTs) with different origins in amyotrophic lateral sclerosis (ALS) using neurite orientation dispersion and density imaging (NODDI). Diffusion-weighted imaging data acquired from 39 patients with ALS and 50 controls were used to estimate NODDI and diffusion tensor imaging (DTI) models. Fine maps of CST subfibers originating from the primary motor area (M1), premotor cortex, primary sensory area, and supplementary motor area (SMA) were segmented. NODDI metrics (neurite density index [NDI] and orientation dispersion index [ODI]) and DTI metrics (fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) were computed. The patients with ALS showed microstructural impairments (reflected by NDI, ODI, and FA reductions and MD, AD, and RD increases) in CST subfibers, especially in M1 fibers, which correlated with disease severity. Compared with other diffusion metrics, NDI yielded a higher effect size and detected the greatest extent of CST subfibers damage. Logistic regression analyses based on NDI in M1 subfiber yielded the best diagnostic performance compared with other subfibers and the whole CST. Microstructural impairment of CST subfibers (especially those originating from M1) is the key feature of ALS. The combination of NODDI and CST subfibers analysis may improve diagnosing performance for ALS.

Transcriptome analysis reveals reasons for the low tolerance of Clostridium tyrobutyricum to furan derivatives.

Lignocellulosic biomass is considered the most abundant and renewable feedstock for biobased butyric acid production. However, the furan derivatives (FAs, mainly furfural and 5-hydroxymethylfurfural) generated from the pretreatment of lignocellulose severely inhibit the growth of Clostridium tyrobutyricum, which is the best strain for producing butyric acid. The tolerance mechanism of C. tyrobutyricum to FAs has not been investigated thus far. Here, the response of C. tyrobutyricum ATCC 25755 to FA challenge was first evaluated by using comprehensive transcriptional analysis. The results indicated that the genes related to membrane transport, heat shock proteins, and transcriptional regulation were upregulated under FA stress. However, the expression of almost all genes encoding reductases was not changed, and only the ad gene CTK_RS02625 and the bud gene CTK_RS07810 showed a significant increase of ~ 1.05-fold. Then, the enzyme activity assays indicated that BUD could catalyze the reduction of FAs with relatively low activity and that AD could not participate in the conversion of FAs, indicating that the inability to rapidly convert FAs to their low-toxicity alcohols may be the main reason for the low FA tolerance of C. tyrobutyricum. This research provides insights into the development of FA-tolerant strains, thereby enhancing the bioconversion of lignocellulosic biomass to butyric acid. KEY POINTS: • The response of C. tyrobutyricum to FAs was evaluated for the first time. • Genes encoding membrane transporters and heat shock proteins were triggered by FAs. • A lack of effective FA reductases leads to low FA tolerance in C. tyrobutyricum.

Spinal cord involvement in MOGAD, AQP4-Ab NMOSD &amp; MS

IntroductionSpinal cord involvement is important in aquaporin-4(AQP4) antibody(Ab)-positive neuro- myelitis optica spectrum disorder(NMOSD), myelin-oligodendrocyte glycoprotein-Ab disease(MOGAD) and multiple sclerosis(MS).MethodsData from adults with spinal cord involvement and MOGAD(n=46) or AQP4-Ab(n=69) were retrospectively analysed. An additional c-spine MRI (3DT1,3DT2,2D axial T2*,DTI,MTR) was performed and analysed using SCT and FSL on 20 patients from each cohort, together with 20 MS and 20 healthy volunteers(HV).ResultsCompared to AQP4-Ab, MOGAD patients had more short lesions(p≤0.0001) and multiple lesions(p≤0.001). In AQP4-Ab, age was the most important factor affecting long-term outcome; while in MOGAD it was the presence of a brainstem lesion at the time of the myelitis. In the cervical cord MRI study, the MOGAD group had no residual lesions, and did not show a significant reduction in either CSA, FA or MTR, but showed a reduction of grey matter volume in those with cervical cord involvement(p=0.0229). The AQP4-Ab group showed a significantly reduced CSA(p=0.0288) and FA(p=0.0085) and a reduced MTR compared to both HV(p≤0.0001) and MOGAD(p=0.0096). This was driven by those with cervical cord lesions. The MS group had a significantly reduced FA(p=0.0204), GM(p=0.0133) and MTR(p=0.0106). FA associated with EDSS(p=0.02,R2=0.25) in the corticospinal tract and pain in the spinothalamic tract(p≤0.01,R2=0.32). Overall, CSA was the strongest predictor of EDSS.ConclusionMOGAD may predominantly affect the grey matter. AQP4-Ab disease shows the most severe, localised cord damage. MRI metrics do not discriminate these conditions but show clinical significance.romina.mariano@ndcn.ox.ac.uk

Segmental alterations of the corpus callosum in motor neuron disease: A DTI and texture analysis in 575 patients

IntroductionWithin the core neuroimaging signature of amyotrophic lateral sclerosis (ALS), the corpus callosum (CC) is increasingly recognized as a consistent feature. The aim of this study was to investigate the sensitivity and specificity of the microstructural segmental CC morphology, assessed by diffusion tensor imaging (DTI) and high-resolution T1-weighted (T1w) imaging, in a large cohort of ALS patients including different clinical phenotypes. MethodsIn a single-centre study, 575 patients with ALS (classical phenotype, N = 432; restricted phenotypes primary lateral sclerosis (PLS) N = 55, flail arm syndrome (FAS) N = 45, progressive bulbar palsy (PBP) N = 22, lower motor neuron disease (LMND) N = 21) and 112 healthy controls underwent multiparametric MRI, i.e. volume-rendering T1w scans and DTI. Tract-based fractional anisotropy statistics (TFAS) was applied to callosal tracts of CC areas I-V, identified from DTI data (tract-of-interest (TOI) analysis), and texture analysis was applied to T1w data. In order to further specify the callosal alterations, a support vector machine (SVM) algorithm was used to discriminate between motor neuron disease patients and controls. ResultsThe analysis of white matter integrity revealed predominantly FA reductions for tracts of the callosal areas I, II, and III (with highest reductions in callosal area III) for all ALS patients and separately for each phenotype when compared to controls; texture analysis demonstrated significant alterations of the parameters entropy and homogeneity for ALS patients and all phenotypes for the CC areas I, II, and III (with again highest reductions in callosal area III) compared to controls. With SVM applied on multiparametric callosal parameters of area III, a separation of all ALS patients including phenotypes from controls with 72% sensitivity and 73% specificity was achieved. These results for callosal area III parameters could be improved by an SVM of six multiparametric callosal parameters of areas I, II, and III, achieving a separation of all ALS patients including phenotypes from controls with 84% sensitivity and 85% specificity. DiscussionThe multiparametric MRI texture and DTI analysis demonstrated substantial alterations of the frontal and central CC with most significant alterations in callosal area III (motor segment) in ALS and separately in all investigated phenotypes (PLS, FAS, PBP, LMND) in comparison to controls, while no significant differences were observed between ALS and its phenotypes. The combination of the texture and the DTI parameters in an unbiased SVM-based approach might contribute as a neuroimaging marker for the assessment of the CC in ALS, including subtypes.

Widespread Disruptions of White Matter in Familial Multiple Sclerosis: DTI and NODDI Study.

Diffusion tensor imaging (DTI) is a noninvasive, quantitative MRI technique that measures white matter (WM) integrity. Many brain dimensions are heritable, including white matter integrity measured with DTI. Family studies are valuable to provide insights into the interactive effects of non-environmental factors on multiple sclerosis (MS). To examine the contribution of familial factors to the diffusion signals across WM microstructure, we performed DTI and calculated neurite orientation dispersion plus density imaging (NODDI) diffusion parameters in two patient groups comprising familial and sporadic forms of multiple sclerosis and their unaffected relatives. We divided 111 subjects (49 men and 62 women: age range 19–60) into three groups conforming to their MS history. The familial MS group included 30 participants (patients; n = 16, healthy relatives; n = 14). The sporadic group included 41 participants (patients; n = 10, healthy relatives; n = 31). Forty age-matched subjects with no history of MS in their families were defined as the control group. To study white matter integrity, two methods were employed: one for calculating the mean of DTI, FA, and MD parameters on 18 tracts using Tracts Constrained by Underlying Anatomy (TRACULA) and the other for whole brain voxel-based analysis using tract-based spatial statistics (TBSS) on NDI and ODI parameters derived from NODDI and DTI parameters. Voxel-based analysis showed considerable changes in FA, MD, NDI, and ODI in the familial group when compared with the control group, reflecting widespread impairment of white matter in this group. The analysis of 18 tracts with TRACULA revealed increased MD and FA reduction in more tracts (left and right ILF, UNC, and SLFT, forceps major and minor) in familial MS patients vs. the control group. There were no significant differences between the patient groups. We found no consequential changes in healthy relatives of both patient groups in voxel-based and tract analyses. Considering the multifactorial etiology of MS, familial studies are of great importance to clarify the effects of certain predisposing factors on demyelinating brain pathology.

Functional and Oxidative Quality Characterization of Spray-Dried Omega-3-Enriched Milk Powder

In the present study, fish oil (FO) and wall material were supplemented to milk to produce spray-dried powder (SDP). Furthermore, the mandate of the study was to enlighten the effect of spray-drying (SD) operating conditions on functional and oxidative quality of produced SDP samples. Purposefully, the cow milk was supplemented with 3% FO as omega-enriched source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for development of milk and FO blends (MFOBs). The lecithin was used as an emulsifier and maltodextrin was supplemented as the wall material (WM) in the MFOBs. Initially, the FO, milk fat (MF), and MFOB samples were characterized for EPA, DHA, and peroxide value (PV) before the SD. The SD of MFOB samples was carried out to produce SDP samples by using a mini spray dryer. Central composite design (CCD) with face-centered rotation was used to optimize SD independent conditions such as inlet air temperature (IAT), pump speed (PS), maltodextrin percentage (MD), and needle speed (NS) in the ranges of 160–200°C, 3–9 mL/min, 10–30%, and 5–9 s, respectively. The encapsulation efficiency (EE) ranged between 89.30 and 81.57%. The EPA and DHA retentions were in the ranges of 2.19–1.87 g/100 g and 3.20–2.75 g/100 g, respectively. The highest results for responses were observed on the following conditions: IAT was 160°C, PS was 9 mL/min, MD was 30%, and NS was 9 s, respectively; the minimum values of response factors were obtained on the following conditions: IAT was 200°C, PS was 3 mL/min, MD was 10%, and NS was 5 s, respectively. The percent losses of EPA and DHA were noted in the range of 2–18%. The IAT was observed as main factor for FA reduction in SDP samples. The SDP samples were stable, and low rate of peroxide values was noted. Overall, spray drying can be potentially used to incorporate the essential fatty acids in milk to produce stable SDP for food applications.

Extra-motor manifestations in post-polio syndrome (PPS): fatigue, cognitive symptoms and radiological features.

There is a paucity of cerebral neuroimaging studies in post-polio syndrome (PPS), despite the severity of neurological and neuropsychological sequelae associated with the condition. Fatigue, poor concentration, limited exercise tolerance, paraesthesia and progressive weakness are frequently reported, but the radiological underpinnings of these symptoms are poorly characterised. The aim of this study is to evaluate cortical and subcortical alterations in a cohort of adult polio survivors to explore the anatomical substrate of extra-motor manifestations. Thirty-six patients with post-polio syndrome, a disease-control group with amyotrophic lateral sclerosispatients and a cohort of healthy individuals were included in a prospective neuroimaging study with a standardised clinical and radiological protocol. Validated clinical instruments were utilised to assess mood, cognitive and behavioural domains and specific aspects of fatigue. Cortical thickness analyses, subcortical volumetry, brainstem segmentation and region-of-interest(ROI) white matter analyses were undertaken to assess regional grey and white matter alterations. A high proportion of PPS patients exhibited apathy, verbal fluency deficits and reported self-perceived fatigue. On ROI analyses, cortical atrophy was limited to the cingulate gyrus, and the temporal pole and subcortical atrophy were only detected in the left nucleus accumbens. No FA reductions were noted to indicate white matter degeneration in any of the lobes. Despite the high incidence of extra-motor manifestations in PPS, only limited cortical, subcortical and white matter degeneration was identified. Our findings suggest that non-structural causes, such as polypharmacy and poor sleep, may contribute to the complex symptomatology of post-polio syndrome.

Impairments of white matter tracts and connectivity alterations in five cognitive networks of patients with multiple sclerosis

IntroductionMS is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention, memory, and speed of information processing. Here, we analyzed the white matter damage and topological organization of white matter tracts in specific brain regions responsible for cognition in MS. MethodsBrain DTI, rs-fMRI, T1, T2, and T2-FLAIR were acquired for 22 MS subjects and 22 healthy controls. Automatic brain parcellation was performed on T1-weighted images. Skull-stripped T1-weighted intensity inverted images were co-registered to the b0 image. Diffusion-weighted images were processed to perform whole brain tractography. The rs-fMRI data were processed, and the connectivity matrixes were analyzed to identify significant differences in the network of nodes between the two groups using NBS analysis. In addition, diffusion entropy maps were produced from DTI data sets using in-house software. ResultsMS subjects exhibited significantly reduced mean FA and entropy in 38 and 34 regions, respectively, out of a total of 54 regions. The connectivity values in both structural and functional analyses were decreased in most regions of the default mode network and in four other cognitive networks in MS subjects compared to healthy controls. MS also induced significant reduction in the normalized hippocampus and corpus callosum volumes; the normalized hippocampus volume was significantly correlated with EDSS scores. ConclusionMS subjects have significant white matter damage and reduction of FA and entropy in various brain regions involved in cognitive networks. Structural and functional connectivity within the default mode network and an additional four cognitive networks exhibited significant changes compared with healthy controls.

Interrogation of chemical changes on, and through, the bacterial envelope of Escherichia coli FabF mutant using time‐of‐flight secondary ion mass spectrometry

Time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) using a primary ion beam of (CO2)6k+ was used to analyse chemical changes in the bacterial envelope of a fabF knock‐out Escherichia coli strain. fabF is the gene coding for FabF, the enzyme involved in the elongation of FA(16:1) to FA(18:1) and has been associated with plasmid transfer that can lead to acquired multiantibiotic resistance. Comparison of the membrane composition between fabF mutant E. coli and wild type E. coli during the logarithmic and stationary growth phases at two culture temperatures (37°C and 30°C) revealed substantial depletion of FA(18:1) in the fabF mutant during logarithmic growth that resulted in a correlated reduction in FA(cp19:0) during stationary phase. While no clear temperature dependence on the effect of the fabF mutation was found, a reduction in cyclopropanation was observed at lower culture temperature in the wild type strain. Additionally, depth profile analysis revealed a ‘thickening’ of the lipid A layer on the surface of the bacteria during stationary phase and also the appearance of cyclic enterobacterial common antigen (ECACYC) below the surface of the bacteria upon the shift from logarithmic to stationary growth phase.

White Matter Integrity According to the Stage of Mental Disorder in Youth

The present study investigated differences in white matter (WM) integrity between 96 young people with affective and/or psychotic symptoms classified at an early stage of mental disorder (i.e. ‘attenuated syndrome’; stage 1b), 85 young people classified at a more advanced stage of mental disorder (i.e. ‘discrete disorder’; stage 2), and 81 demographically matched healthy controls using diffusion tensor imaging. The relationship between WM integrity (indexed by fractional anisotropy; FA) across the tracts and neuropsychological functioning was also investigated. A significant reduction in FA was identified in those with more advanced disorder in the body of the corpus callosum. Clinical stage groups were associated with significant neuropsychological impairment, which was significantly greater in those with discrete disorders. Compared to those in the earlier stage of disorder, participants at the later clinical stage showed decreased FA in the body of the corpus callosum that was associated with worse performance in attentional set formation maintenance, shifting and flexibility. These results provide further support for clinical staging of mental disorder and highlight the potential for utilising neuroanatomical biomarkers to support the classification of stages of mental disorder in the future.

Macrophage maturation from blood monocytes is altered in people with HIV, and is linked to serum lipid profiles and activation indices: A model for studying atherogenic mechanisms.

People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Proportions of vascular homing monocytes are enriched in PWH; however, little is known regarding monocyte-derived macrophages (MDMs) that may drive atherosclerosis in this population. We isolated PBMCs from people with and without HIV, and cultured these cells for 5 days in medium containing autologous serum to generate MDMs. Differential gene expression (DGE) analysis of MDMs from PWH identified broad alterations in innate immune signaling (IL-1β, TLR expression, PPAR βδ) and lipid processing (LXR/RXR, ACPP, SREBP1). Transcriptional changes aligned with the functional capabilities of these cells. Expression of activation markers and innate immune receptors (CD163, TLR4, and CD300e) was altered on MDMs from PWH, and these cells produced more TNFα, reactive oxygen species (ROS), and matrix metalloproteinases (MMPs) than did cells from people without HIV. MDMs from PWH also had greater lipid accumulation and uptake of oxidized LDL. PWH had increased serum levels of free fatty acids (FFAs) and ceramides, with enrichment of saturated FAs and a reduction in polyunsaturated FAs. Levels of lipid classes and species that are associated with CVD correlated with unique DGE signatures and altered metabolic pathway activation in MDMs from PWH. Here, we show that MDMs from PWH display a pro-atherogenic phenotype; they readily form foam cells, have altered transcriptional profiles, and produce mediators that likely contribute to accelerated ASCVD.

White matter disruption in obsessive-compulsive disorder revealed by meta-analysis of tract-based spatial statistics.

Exploring white matter (WM) microstructural alterations is a momentous step for gaining insights about underlying mechanisms of obsessive-compulsive disorder (OCD) and improving the efficacy of therapies for this condition. Many tract-based spatial statistics (TBSS) studies have revealed abnormalities of fractional anisotropy (FA; an index of WM integrity) in OCD. However, research works have not drawn robust conclusions. Therefore, we integrated the findings of TBSS studies to identify the most consistent FA changes in OCD using meta-analytical approach. Online databases were systematically searched for all TBSS studies comparing FA between patients with OCD and controls. A coordinate-based meta-analysis was performed using anisotropic effect size version of the seed-based d mapping software. Meanwhile, meta-regression was used to explore the potential association of clinical characteristics with regional FA abnormalities. Our meta-analysis included 488 OCD patients and 519 controls across 17 datasets. FA reductions were identified in the genu of the corpus callosum and the left orbitofrontal WM in OCD patients relative to controls. Metaregression analyses showed that the FA in the left orbitofrontal WM was negatively and independently correlated with symptom severity and illness duration in patients withOCD. The current study provides a quantitative overview of TBSS findings in OCD and demonstrates the most prominent and replicable WM abnormalities in OCD are in the anterior part of the brain including interhemispheric connection and orbitofrontal region. Additionally, our findings suggest that FA reduction in the orbitofrontal WM might be a potential biomarker in predicting disease severity and progression in patients with OCD.

What can DTI add in acute ischemic stroke patients?

BackgroundCerebrovascular stroke is one of the leading causes of death worldwide. Imaging with conventional MR techniques cannot provide reliable information as regard the integrity of the white matter tracts and therefore limiting its ability to predict the clinical outcome. While prediction of the motor outcome becomes more crucial for determining the specific rehabilitation strategies and final clinical outcomes, the purpose of this study was to assess the value of diffusion tensor MR imaging in patients with acute ischemic stroke as a prognostic imaging modality to predict the clinical outcome.ResultsA significant statistical association was found between the tractography findings and the clinical score at admission (p 0.0005) and the clinical recovery after 3 months (p 0.001). Residual neurological deficits were found in patients with disrupted tracts; on the other hand, near complete clinical recovery was found in patients with non-disrupted tracts. Also, significant statistical association was found between the degree of FA reduction in the affected tracts and the clinical score at admission (p 0.001) and the clinical recovery after 3 months (p 0.01). Correlation between the FA values at the site of infarctions and the corresponding area of the brain on the contralateral side revealed significant statistical difference.ConclusionDTI offers a potential tool for prediction of the clinical outcome of acute stroke patients as it can detect the microstructural changes in the white matter tracts affected by the ischemic lesions which cannot be detected by conventional MRI and therefore can help in determining the rehabilitation strategy

Voxel-based diffusion tensor imaging in focal epilepsies: comparative analyses of microstructural damage in pharmacoresponse of mesial temporal lobe epilepsy and frontal lobe epilepsy

The diffusion tensor image (DTI) is an MRI technique that allows noninvasive evaluation of white matter (WM). It describes the magnitude (mean diffusivity-MD) and directionality (fractional anisotropy-FA) of the movement of water molecules. Widespread WM changes measured by DTI has been described in focal epilepsies, however their relation to the etiology and pharmacological response is unclear. To analyze DTI images in pharmacoresponsive or pharmacoresistant patients with mesial temporal lobe epilepsy (gMTLE and rMTLE, respectively), all with hippocampal sclerosis (HS), frontal lobe epilepsy (FLE) with focal cortical dysplasia (FCD) and normal controls. We enrolled 97 patients (29 with gMTLE, 48 with rMTLE, 20 with FLE-FCD) and 70 controls. MRI was performed on a Phillips 3.0 T scanner. The DTI images were processed using MRICloud.org. We applied Kruskall-Wallis with Dunn-Bonferroni post-hoc comparisons to examine FA and MD values in regions-of-interest (ROI). We set p<0.05 as significant, corrected for false discovery rate. We found a significant reduction in ipsilateral and contralateral FA, and an increase of MD in both groups of patients with MTLE in almost all ROIs compared to controls. Patients with FLE-FCD had less diffuse DTI changes, consisting mainly by bilateral FA reduction in corpus callosum compared to controls (Table 1). WM microstructural are more widespread in patients with MTLE-HS than in FLE-FCD. gMTLE and rMTLE patients presented similar patterns of abnormalities. However, rMTLE patients had WM more intense changes in limbic tracts.

Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis

Extracellular β-amyloid (Aβ) plaque deposits and inflammatory immune activation are thought to alter various aspects of tissue microstructure, such as extracellular free water, fractional anisotropy and diffusivity, as well as the density and geometric arrangement of axonal processes. Quantifying these microstructural changes in Alzheimer’s disease and related neurodegenerative dementias could serve to monitor or predict disease course. In the present study we used high-field diffusion magnetic resonance imaging (dMRI) to investigate the effects of Aβ and inflammatory interleukin-6 (IL6), alone or in combination, on in vivo tissue microstructure in the TgCRND8 mouse model of Alzheimer’s-type Aβ deposition. TgCRND8 and non-transgenic (nTg) mice expressing brain-targeted IL6 or enhanced glial fibrillary protein (EGFP controls) were scanned at 8 months of age using a 2-shell, 54-gradient direction dMRI sequence at 11.1 T. Images were processed using the diffusion tensor imaging (DTI) model or the neurite orientation dispersion and density imaging (NODDI) model. DTI and NODDI processing in TgCRND8 mice revealed a microstructure pattern in white matter (WM) and hippocampus consistent with radial and longitudinal diffusivity deficits along with an increase in density and geometric complexity of axonal and dendritic processes. This included reduced FA, mean, axial and radial diffusivity, and increased orientation dispersion (ODI) and intracellular volume fraction (ICVF) measured in WM and hippocampus. IL6 produced a ‘protective-like’ effect on WM FA in TgCRND8 mice, observed as an increased FA that counteracted a reduction in FA observed with endogenous Aβ production and accumulation. In addition, we found that ICVF and ODI had an inverse relationship with the functional connectome clustering coefficient. The relationship between NODDI and graph theory metrics suggests that currently unknown microstructure alterations in WM and hippocampus are associated with diminished functional network organization in the brain.

SIRT1 negatively regulates invasive and angiogenic activities of the extravillous trophoblast

Dysregulation of extravillous trophoblast (EVT) invasion leads to pregnancy complications, such as pre-eclampsia, fetal growth restriction, and placenta accreta. The aim of this study was to explore the role of SIRT1 in EVT invasion and its underlying mechanism. SIRT1-specific siRNA was transfected into Swan 71 cells, an immortalized first trimester trophoblast cell line. The Boyden chamber invasion assay, the scratch wound healing assay, and cell proliferation assay were performed. The expression levels of epithelial-to-mesenchymal transition (EMT) markers, matrix metalloproteinase-2 (MMP-2), MMP-9, p-Akt, Akt, p-p38MAPK, p38MAPK, p-ERK, ERK, p-JNK, JNK, Fas, and Fas ligand (FasL) were examined by western blot. Tube formation assay was conducted by using Matrigel. SIRT1 knockdown by siRNA significantly enhanced invasion and migration as well as the expression of MMP-2, MMP-9, and EMT markers in Swan 71 cells, but reduced proliferation. The effects of SIRT1 knockdown on invasion, migration, proliferation, and endothelial-like tube formation in Swan 71 cells were reversely regulated by blockade of Akt and p38MAPK signaling. In addition, SIRT1 knockdown markedly promoted colocalization of Swan 71 cells to human umbilical vein endothelial cell (HUVEC) networks and induced reduction in Fas and enhancement of FasL. Conditioned media of SIRT1 knockdown-Swan 71 cells caused reduction in cell proliferation and augmentation of cytotoxicity along with increased Fas expression in HUVECs. Our results suggest that SIRT1 may be associated with placental development by controlling EVT invasion and spiral artery remodeling via modulation of EMT, MMP-2, MMP-9, Akt/p38MAPK signaling, and Fas/FasL.