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IntroductionWe investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.MethodsWe included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols.ResultsHigher sOB-R was associated with lower fractional anisotropy (FA, β = -0.114 ± 0.02, p

Background: Intervertebral disc (IVD) degeneration is the main cause of neck pain. Although conventional magnetic resonance imaging can detect morphological changes in intervertebral disc degeneration, it cannot provide accurate and objective evaluations. Magnetic resonance diffusion tensor imaging (DTI) reflects the microstructural changes in tissues by describing the diffusion of water molecules. It was initially applied to the evaluation of lumbar disc degeneration; however, no study has used DTI to evaluate cervical disc degeneration. Objective: To conduct a prospective study to evaluate the efficacy and feasibility of DTI in quantifying cervical disc degeneration by correlating the main parameters of axial DTI of intervertebral discs, namely fractional anisotropy (FA) and mean diffusivity (MD) values, using the Pfirrmann grade. Methods: The cervical discs of 30 symptomatic volunteers with neck pain and 20 asymptomatic volunteers were assessed using a 3.0 T magnetic resonance scanner. We evaluated intervertebral discs from C3/4 to C6/7 in each volunteer. The Pfirrmann grades, FA value, and MD value on the conventional magnetic resonance imaging were evaluated. The Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the FA and MD values of subjects with different degeneration levels. Results: Statistical analysis showed that the FA value of the nucleus pulposus in patients group was significantly higher than that in the asymptomatic volunteers, and the MD value of the nucleus pulposus was significantly lower than that in the asymptomatic volunteers, and the difference was significant (P < 0.05). In the study group, with an increase in cervical intervertebral disc grade, the FA value of the nucleus pulposus also showed a gradual upward trend, and this difference was significant (P < 0.05). The MD value of the nucleus pulposus showed a gradual downward trend, except between grades I and II, which indicates that the axial FA value can better show the early pathological changes of the cervical intervertebral disc. Conclusions: The FA and MD values of the cervical intervertebral disc can quantitatively evaluate the degree of degeneration of the cervical intervertebral disc; axial DTI imaging technology can provide a good theoretical basis for the imaging diagnosis of cervical intervertebral disc degeneration and has important clinical application value. [ABSTRACT FROM AUTHOR]

Background and Aims Microstructural disturbances underlie dysfunctional contraction and adverse left ventricular (LV) remodelling after ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) quantifies dynamic reorientation of sheetlets (E2A) from diastole to systole during myocardial thickening, and markers of tissue integrity [mean diffusivity (MD) and fractional anisotropy (FA)]. This study investigated whether microstructural alterations identified by biphasic DT-CMR: (i) enable contrast-free detection of acute myocardial infarction (MI); (ii) associate with severity of myocardial injury and contractile dysfunction; and (iii) predict adverse LV remodelling. Methods Biphasic DT-CMR was acquired 4 days (n = 70) and 4 months (n = 66) after reperfused STEMI and in healthy volunteers (HVOLs) (n = 22). Adverse LV remodelling was defined as an increase in LV end-diastolic volume ≥ 20% at 4 months. MD and FA maps were compared with late gadolinium enhancement images. Results Widespread microstructural disturbances were detected post-STEMI. In the acute MI zone, diastolic E2A was raised and systolic E2A reduced, resulting in reduced E2A mobility (all P <.001 vs. adjacent and remote zones and HVOLs). Acute global E2A mobility was the only independent predictor of adverse LV remodelling (odds ratio.77; 95% confidence interval.63–.94; P =.010). MD and FA maps had excellent sensitivity and specificity (all > 90%) and interobserver agreement for detecting MI presence and location. Conclusions Biphasic DT-CMR identifies microstructural alterations in both diastole and systole after STEMI, enabling detection of MI presence and location as well as predicting adverse LV remodelling. DT-CMR has potential to provide a single contrast-free modality for MI detection and prognostication of patients after acute STEMI. [ABSTRACT FROM AUTHOR]

Background/Objectives: Although multiple magnetic resonance imaging (MRI) indices are known to be sensitive to the noninvasive assessment of myelin integrity, their relative sensitivities have not been directly compared. This study aimed to identify the most sensitive MRI index for characterizing myelin composition in the spinal cord's gray matter (GM) and white matter (WM). Methods: MRI was performed on a deer's ex vivo cervical spinal cord. Quantitative indices known to be sensitive to myelin, including the myelin water fraction (MWF), magnetization transfer ratio (MTR), the signal ratio between T1- and T2-weighted images (T1W/T2W), fractional anisotropy (FA), mean diffusivity (MD), electrical conductivity (σ), and T1, T2, and T1ρ relaxation times were calculated. Their mean values were compared using repeated measures analysis of variance (ANOVA) and post hoc Bonferroni tests or Friedman and post hoc Wilcoxon tests to identify differences across GM and WM columns possessing distinct myelin distributions, as revealed by histological analysis. Relationships among the indices were examined using Spearman's rank-order correlation analysis. Corrected p < 0.05 was considered statistically significant. Results: All indices except σ differed significantly between GM and all WM columns. Two of the three WM columns had significantly different MWF, FA, MD, and T2, whereas one WM column had significantly different MTR, σ, T1, and T1ρ from the others. A significant moderate to very strong correlation was observed among most indices. Conclusions: The sensitivity of MRI indices in distinguishing spinal cord regions varied. A strategic combination of two or more indices may allow the accurate differentiation of spinal cord regions. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offsprings brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offsprings brain during in utero development. METHODS: We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity. RESULTS: High maternal pre-pregnancy BMI was associated with higher mean MD values in the infants left caudate nucleus. Results remained unchanged after the adjustment for covariates. CONCLUSIONS: In utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infants left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring.

BackgroundChildhood disadvantage is a prominent risk factor for cognitive and brain aging. Childhood disadvantage is associated with poorer episodic memory in late midlife and functional and structural brain abnormalities in the default mode network (DMN). Although age-related changes in DMN are associated with episodic memory declines in older adults, it remains unclear if childhood disadvantage has an enduring impact on this later-life brain-cognition relationship earlier in the aging process. Here, within the DMN, we examined whether its cortical microstructural integrity-an early marker of structural vulnerability that increases the risk for future cognitive decline and neurodegeneration-is associated with episodic memory in adults at ages 56-66, and whether childhood disadvantage moderates this association.MethodsCortical mean diffusivity (MD) obtained from diffusion magnetic resonance imaging was used to measure microstructural integrity in 350 community-dwelling men. We examined both visual and verbal episodic memory in relation to DMN MD and divided participants into disadvantaged and nondisadvantaged groups based on parental education and occupation.ResultsHigher DMN MD was associated with poorer visual memory but not verbal memory (β = -0.11, p = .040 vs β = -0.04, p = .535). This association was moderated by childhood disadvantage and was significant only in the disadvantaged group (β = -0.26, p = .002 vs β = -0.00, p = .957).ConclusionsLower DMN cortical microstructural integrity may reflect visual memory vulnerability in cognitively normal adults earlier in the aging process. Individuals who experienced childhood disadvantage manifested greater vulnerability to cortical microstructure-related visual memory dysfunction than their nondisadvantaged counterparts who exhibited resilience in the face of low cortical microstructural integrity.

Abstract To determine diagnostic value of diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients and investigate the association between DTI and neurofilaments (NFs), including serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). Forty-three clinically diagnosed ALS patients and 32 control subjects without neurological disorders underwent routine MRI (magnetic resonance imaging) and DTI scans. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) at axial levels of internal capsules and cerebral peduncles along the corticospinal tract (CST) were measured. The study compared the differences of DTI parameters between ALS patients and controls using the Mann-Whitney U test. Diagnostic efficacy of each DTI metric was evaluated using the receiver operating characteristic (ROC) curve. NFs (NFL and pNFH levels in serum and CSF) were measured by enzyme-linked immunosorbent assay. Correlation analyses were conducted between DTI parameters and NFs. Capsule-MD and Peduncle-MD in ALS patients were higher than those in controls; whereas Capsule-FA and Peduncle-FA in ALS patients were lower than those in controls (all, p

Introduction: This research aimed to investigate the pathophysiological mechanism of how drug-induced parkinsonism (DIP) affects the integrity of the white matter (WM) fiber microstructure as measured by magnetic resonance diffusion tensor image (DTI) fractional anisotropy (FA) and mean diffusivity (MD). Methods: We recruited 17 participants diagnosed with DIP, 20 Parkinson's disease (PD) patients, and 16 normal controls (NCs) with a similar age, gender, and years of education. Subsequently, all participants underwent DTI magnetic resonance imaging scanning. To analyze the data, we utilized the software packages Functional MRI of the Brain Centre (FMRIB) Diffusion Toolbox (FDT), developed by the FMRIB laboratory at Oxford University, and tract-based spatial statistics (TBSS). Results: The Argentina Hyposmia Rating Scale (AHRS) scores of patients in DIP group were markedly higher than those in PD patients group. Compared with the NC group, the FA values in the genu and body of the corpus callosum (CC), anterior limb of the right internal capsule, bilateral anterior corona radiata, bilateral superior corona radiata, right external capsule, and right superior fronto-occipital fasciculus (could be a part of the anterior internal capsule) were significantly decreased in the DIP group; however, no significant cluster was found in MD. Conclusions: The present study provides novel insights into the alterations in WM microstructure among DIP patients, suggesting that these methodologies have the potential to aid in the early diagnosis and treatment of DIP. [ABSTRACT FROM AUTHOR]

To determine diagnostic value of diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients and investigate the association between DTI and neurofilaments (NFs), including serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). Forty-three clinically diagnosed ALS patients and 32 control subjects without neurological disorders underwent routine MRI (magnetic resonance imaging) and DTI scans. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) at axial levels of internal capsules and cerebral peduncles along the corticospinal tract (CST) were measured. The study compared the differences of DTI parameters between ALS patients and controls using the Mann-Whitney U test. Diagnostic efficacy of each DTI metric was evaluated using the receiver operating characteristic (ROC) curve. NFs (NFL and pNFH levels in serum and CSF) were measured by enzyme-linked immunosorbent assay. Correlation analyses were conducted between DTI parameters and NFs. Capsule-MD and Peduncle-MD in ALS patients were higher than those in controls; whereas Capsule-FA and Peduncle-FA in ALS patients were lower than those in controls (all, p < 0.05). The area under curve (AUC) was 0.730 for Capsule-FA, 0.828 for Capsule-MD, 0.890 for Peduncle-FA, and 0.896 for Peduncle-MD. Capsule-FA was negatively correlated with CSF-NFL (r = − 0.813, p < 0.001), Serum-NFL (r = − 0.493, p = 0.001), CSF-pNFH (r = − 0.637, p < 0.001), and Serum-pNFH (r = − 0.672, p < 0.001); Peduncle-FA negatively with CSF-NFL (r = − 0.562, p < 0.001), CSF-pNFH (r = − 0.506, p = 0.001), and Serum-pNFH (r = − 0.488, p = 0.001); Peduncle-MD positively with CSF-NFL (r = 0.516, p < 0.001), CSF-pNFH (r = 0.494, p = 0.001). DTI had superior performance in identifying ALS patients and could serve as a reliable predictor. DTI parameters related to neurofilament markers, and Capsule-FA may become a robust surrogate biomarker indicating disease severity and progression rate for ALS patients. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. Methods: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. Results: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. Conclusion: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD. [ABSTRACT FROM AUTHOR]

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51-60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes.

BackgroundComposite scores of magnetic resonance imaging-derived metrics in brain regions associated with Alzheimer's disease (AD), commonly termed AD signatures, have been developed to distinguish early AD-related atrophy from normal age-associated changes. Diffusion-based gray matter signatures may be more sensitive to early AD-related changes compared with thickness/volume-based signatures, demonstrating their potential clinical utility. The timing of early (i.e., midlife) changes in AD signatures from different modalities and whether diffusion- and thickness/volume-based signatures each capture unique AD-related phenotypic or genetic information remains unknown.MethodsOur validated thickness/volume signature, our novel mean diffusivity (MD) signature, and a magnetic resonance imaging-derived measure of brain age were used in biometrical analyses to examine genetic and environmental influences on the measures as well as phenotypic and genetic relationships between measures over 12 years. Participants were 736 men from 3 waves of the Vietnam Era Twin Study of Aging (VETSA) (baseline/wave 1: mean age [years] = 56.1, SD = 2.6, range = 51.1-60.2). Subsequent waves occurred at approximately 5.7-year intervals.ResultsMD and thickness/volume signatures were highly heritable (56%-72%). Baseline MD signatures predicted thickness/volume signatures over a decade later, but baseline thickness/volume signatures showed a significantly weaker relationship with future MD signatures. AD signatures and brain age were correlated, but each measure captured unique phenotypic and genetic variance.ConclusionsCortical MD and thickness/volume AD signatures are heritable, and each signature captures unique variance that is also not explained by brain age. Moreover, results are in line with changes in MD emerging before changes in cortical thickness, underscoring the utility of MD as a very early predictor of AD risk.

Background: Major brain injuries in structural brain magnetic resonance imaging (MRI) at term affect concurrent diffusion tensor imaging (DTI) parameters in very preterm infants. White matter is known to gradually maturate along with increasing gestational age, which is characterized by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). Purpose: To study the difference between DTI parameters at term and 13 years in adolescents born very preterm with and without major pathologies in structural brain MRI at term. Material and Methods: Adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) in 2004–2006 at Turku University Hospital, Finland were included. We evaluated FA and MD at term and 13 years in 18 regions of interest using the JHU-neonate-SS atlas to compare the differences in these parameters between adolescents with and without major injuries identified on MRI at term. Results: A total of 24 adolescents underwent brain MRI including DTI both at term and 13 years. Adolescents with major brain injury pathologies (n = 6) in structural MRI at term had decreased FA in the left corpus callosum and right cingulate gyrus part, and increased MD in the left corpus callosum, right anterior limb of internal capsule, and right posterior limb of the internal capsule at 13 years, in comparison with adolescents without major brain injuries (n = 18) in structural MRI at term. Conclusion: Our findings suggest that major brain injuries identified on structural MRI at term affect brain maturation, with adverse effects in FA and MD still during adolescence. [ABSTRACT FROM AUTHOR]

Background: Growing evidence of neuroimaging has indicated brain microstructural abnormalities in comitant strabismus. Nonetheless, few studies have investigated neuropathological alterations in patients with intermittent exotropia (IXT). This study aimed at examining the characteristics of brain microstructure along major fiber tracts in IXT patients using an automated fiber quantification analysis. Methods: A total of 25 patients with IXT as well as 25 healthy participants matched for age and gender finished the diffusion tensor imaging scanning and the ophthalmic examination. Automated fiber quantification analysis of 20 major fiber tracts was carried out for IXT patients and healthy subjects, respectively. Diffusion metrics of 100 equidistant nodes resampled along each tract were measured for every subject and compared between two groups. Effect size analysis was performed to identify the most affected fiber tracts in IXT. Results: Widely declined mean diffusivity was noted in IXT along major tracts containing bilateral thalamic radiations, bilateral corticospinal fasciculi, bilateral cingulum cingulate, left inferior fronto-occipital fasciculus, right arcuate fasciculus and superior longitudinal fasciculus. Local reduction in fractional anisotropy was observed in IXT along left cingulum hippocampus, right inferior longitudinal fasciculus and right uncinate fasciculus, in contrast to the regionally increased fractional anisotropy along bilateral thalamic radiation, left corticospinal tract and left arcuate fasciculus. Among the tracts with significantly changed diffusion metrics in IXT, right inferior longitudinal fasciculus was the most affected one in fractional anisotropy while left thalamic radiation was the most influenced one in mean diffusivity. Conclusions: Abnormalities in microstructural properties along visual-related fiber tracts are likely to contribute to difficulties in visual information processing in IXT patients, which could serve as the neural basis of underlying pathological mechanism of IXT.

Introduction: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. Methods: 187 participants were included in this study who were either healthy controls (HC; n = 50) or had early mild cognitive impairment (EMCI; n = 50), late MCI (LMCI; n = 37), or AD (n = 50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. Results: NBM volume was smallest in AD followed by LMCI (p

Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m2 ; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m2 ; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.

Abstract Background Smartphones provide various functions that facilitate our communication, organization, and entertainment in different situations. Diffusion tensor imaging (DTI) is a method measuring tissue microstructure as well as white matter integrity of the brain and detecting early changes. Several research studies recently aim to utilize conventional MRI for assessing brain structural alterations among smartphone users, but our study was aimed at identifying the DTI value while assessing white matter alterations in Egyptian youth with smartphone dependence. Results Our prospective case–control study involved fifty-three individuals with smart phone dependence (SPD group) as well as twenty-five volunteers who represented the control group. SPD individuals and controls were right-handed. The SPD group mean age exhibited 20.54 ± 1.56 years, while controls exhibited 26.8 ± 15.1 years. When utilizing smart phone addiction scale-short version, SPD group median total score exhibited 33. The diagnostic performance of fornix (fractional anisotropy) FA and external capsule fractional anisotropy (EC FA) regarding area under curve (AUC) exhibited significant increase as opposed to all other tested regions, with a sensitivity of 90.6% as well as a specificity of 96%. While regarding the mean diffusivity (MD), the greatest (AUC) was for EC (0.927, p

Diffusion tensor imaging (DTI) is a promising technique for the visualization of the cervical spinal cord (CSC) in vivo. It provides information about the tissue structure of axonal white matter, and it is thought to be more sensitive than other MR imaging techniques for the evaluation of damage to tracts in the spinal cord. The purpose of this study was to determine the within-participants reliability and error magnitude of measurements of DTI metrics in healthy human CSC. A total of twenty healthy controls (10 male, mean age: 33.9 ± 3.5 years, 10 females, mean age: 47.5 ± 14.4 years), with no family history of any neurological disorders or a contraindication to MRI scanning were recruited over a period of two months. Each participant was scanned twice with an MRI 3 T scanner using standard DTI sequences. Spinal Cord Toolbox (SCT) software was used for image post-processing. Data were first corrected for motion artefact, then segmented, registered to a template, and then the DTI metrics were computed. The within-participants coefficients of variation (CV%), the single and average within-participants intraclass correlation coefficients (ICC) and Bland-Altman plots for WM, VC, DC and LC fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for the cervical spinal cord (between the 2nd and 5th cervical vertebrae). DTI metrics showed poor to excellent within-participants reliability for both single and average ICC and moderate to high reproducibility for CV%, all variation dependent on the location of the ROI. The BA plots showed good within-participants agreement between the scan-rescan values. Results from this reliability study demonstrate that clinical trials using the DTI technique are feasible and that DTI, in particular regions of the cord is suitable for use for the monitoring of degenerative WM changes. • DTI measures reveals poor and excellent within-participants reliability, depending on the ROI. • Within-participants variability of DTI metrics are generally acceptable <20% showing moderate to high reproducibility. • Using an automated segmentation software such as SCT is useful and provides atlas-based information. [ABSTRACT FROM AUTHOR]

Physical activity is a protective factor against brain atrophy, while loss of brain volume could also be a determinant of physical activity. Therefore, we aimed to explore the bidirectional association of physical activity with brain structures in middle-aged and older adults from the UK Biobank. Overall, 3027 participants (62.45 ± 7.27 years old, 51.3% females) had data at two time points. Hippocampal volume was associated with total (β=0.048, p FDR =0.016) and household (β=0.075, p FDR <0.001) physical activity. Global fractional anisotropy (β=0.042, p FDR =0.028) was also associated with household physical activity. In the opposite direction, walking was negatively associated with white matter volume (β=-0.026, p FDR =0.008). All these associations were confirmed by the linear mixed models. Interestingly, sports at baseline were linked to hippocampal and frontal cortex volumes at follow-up but these associations disappeared after adjusting for multiple comparisons (p all >0.104). In conclusion, we found more consistent evidence that a healthier brain structure predicted higher physical activity levels than for the inverse, more established relationship. • The association between brain structure and physical activity seems more consistent. • Hippocampal, and global fractional anisotropy linked to housework at follow-up. • Sports were borderline linked to hippocampal and frontal volumes at follow-up. [ABSTRACT FROM AUTHOR]

Background: Smartphones provide various functions that facilitate our communication, organization, and entertainment in different situations. Diffusion tensor imaging (DTI) is a method measuring tissue microstructure as well as white matter integrity of the brain and detecting early changes. Several research studies recently aim to utilize conventional MRI for assessing brain structural alterations among smartphone users, but our study was aimed at identifying the DTI value while assessing white matter alterations in Egyptian youth with smartphone dependence. Results: Our prospective case–control study involved fifty-three individuals with smart phone dependence (SPD group) as well as twenty-five volunteers who represented the control group. SPD individuals and controls were right-handed. The SPD group mean age exhibited 20.54 ± 1.56 years, while controls exhibited 26.8 ± 15.1 years. When utilizing smart phone addiction scale-short version, SPD group median total score exhibited 33. The diagnostic performance of fornix (fractional anisotropy) FA and external capsule fractional anisotropy (EC FA) regarding area under curve (AUC) exhibited significant increase as opposed to all other tested regions, with a sensitivity of 90.6% as well as a specificity of 96%. While regarding the mean diffusivity (MD), the greatest (AUC) was for EC (0.927, p < 0.001), in which the MD value = 0.825 was the cutoff value and able to diagnose the smart phone dependency with a sensitivity of 92.5% as well as a specificity of 76%. Conclusions: Quantitative DTI parameters (FA, MD) in different white matter regions can diagnose and detect white matter changes in excessive smartphone users even when conventional MRI data are normal. This study demonstrates the recent noninvasive MRI technique value while revealing covered brain white matter alterations in Egyptian youth due to smartphone overuse. [ABSTRACT FROM AUTHOR]

Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity is still not fully understood. Default Mode Network (DMN) areas have been recently demonstrated as selectively involved in sCJD, and functional connectivity has never been investigated in prion diseases. We analyzed the grey matter involvement using a quantitatively multi-parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age-matched healthy controls with a group-wise approach. Differences in mean diffusivity were also examined between the cortical (MM(V)1, MM(V)2C, and VV1) and subcortical (VV2 and MV2K) subgroups of sCJD for those with autopsy data available (n = 27, 73%). We also assessed resting-state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs-fMRI dataset available (n = 17). Decreased diffusivity was predominantly present in posterior cortical regions of the DMN, but also outside of the DMN in temporal areas and in a few limbic and frontal areas, in addition to extensive deep nuclei involvement. Both subcortical and cortical sCJD subgroups showed decreased diffusivity subcortically, whereas only the cortical type expressed significantly decreased diffusivity cortically, mainly in parietal, occipital, and medial-inferior temporal cortices bilaterally. Interestingly, we found abnormally increased connectivity in both dorsal and ventral components of the DMN in sCJD subjects compared with healthy controls. The significance and possible utility of functional imaging as a biomarker for tracking disease progression in prion disease needs to be explored further.

Abstract Background It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring’s brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring’s brain during in utero development. Methods We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity. Results High maternal pre-pregnancy BMI was associated with higher mean MD values in the infant’s left caudate nucleus. Results remained unchanged after the adjustment for covariates. Conclusions In utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infant’s left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring.

Abstract Background Patients with chronic kidney disease (CKD) are at risk of a many of central nervous system complications such as stroke and cognitive impairment. Studies based on diffusion tensor imaging (DTI) confirmed that the integrity of white matter in CKD patients has changed and these alterations can be observed before tissue morphological changes occurring on conventional MRI. Early use of DTI in CKD patients can distinguish early individuals with normal cognitive system function and will develop cognitive impairment in later stages. Results As compared with controls, patients with CKD showed increased MD and decreased FA values in different brain regions with frontal, parietal regions and genu of corpus callosum more affected more than the occipital regions. For combined FA and MD in differentiating cases with CKD, there was statistically significant difference in both thalami, internal capsule, CC, cingulum, ILF and CST as p value

The pathophysiology of migraine remains to be elucidated. We have recently shown that interictal migraineurs exhibit reduced fractional anisotropy (FA) in the root entry zone of the trigeminal nerve when compared to controls, but it is not known if this altered nerve anatomy is associated with changes within the brainstem or higher cortical brain regions. Diffusion tensor imaging of the brain was used to calculate regional measures of structure, including mean diffusivity (MD), axial diffusivity (AX) and radial diffusivity (RD) in addition to voxel-based morphometry of T1-weighted anatomical images. Linear relationships between trigeminal nerve anatomy (FA) and MD throughout the brainstem and/or higher cortical regions were determined in both controls (n = 31, brainstem; n = 38, wholebrain) and interictal migraineurs (n = 32, brainstem; n = 38, wholebrain). Additionally, within the same brain areas, relationships of AX and RD with nerve FA were determined. We found that in both interictal migraine and control participants, decreasing trigeminal nerve FA was associated with significantly increased MD in brainstem regions including the spinal trigeminal nucleus and midbrain periaqueductal gray matter (PAG), and in higher brain regions such as the hypothalamus, insula, posterior cingulate, primary somatosensory and primary visual (V1) cortices. Whereas, both control and migraineur groups individually displayed significant inverse correlations between nerve FA and MD, in migraineurs this pattern was disrupted in the areas of the PAG and V1, with only the control group displaying a significant linear relationship (PAG controls r = -0.58, p = 0.003; migraineurs r = -0.25, p = 0.17 and V1 controls r = -0.52, p = 0.002; migraineurs r = -0.10, p = 0.55). Contrastingly, we found no gray matter volume changes in brainstem or wholebrain areas. These data show that overall, trigeminal nerve anatomy is significantly related to regional brain structure in both controls and migraineurs. Importantly, the PAG showed a disruption of this relationship in migraineurs suggesting that the anatomy and possibly the function of the PAG is uniquely altered in episodic migraine, which may contribute to altered orofacial pain processing in migraine.

Background: Multiple sclerosis (MS) is an important cause of acquired neurological disability in young adults, characterized by multicentric inflammation, demyelination, and axonal damage. Objective: The objective is to investigate white matter (WM) damage progression in a Brazilian MS patient cohort, using diffusion tensor imaging (DTI) post-processed by tract-based spatial statistics (TBSS). Methods: DTI scans were acquired from 76 MS patients and 37 sex-and-age matched controls. Patients were divided into three groups based on disease duration. DTI was performed along 30 non-collinear directions by using a 1.5T imager. For TBSS analysis, the WM skeleton was created, and a 5000 permutation-based inference with a threshold of p <.05 was used, to enable the identification of abnormalities in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Results: Decreased FA and increased RD, MD, and AD were seen in patients compared to controls and a decreased FA and increased MD and RD were seen, predominantly after the first 5 years of disease, when compared between groups. Conclusion: Progressive WM deterioration is seen over time with a more prominent pattern after 5 years of disease onset, providing evidence that the early years might be a window to optimize treatment and prevent disability. [ABSTRACT FROM AUTHOR]

Organophosphate-based chemical agents (OP), including nerve agents and certain pesticides such as paraoxon, are potent acetylcholinesterase inhibitors that cause severe convulsions and seizures, leading to permanent central nervous system (CNS) damage if not treated promptly. The current treatment regimen for OP poisoning is intramuscular injection of atropine sulfate with an oxime such as pralidoxime (2-PAM) to mitigate cholinergic over-activation of the somatic musculature and autonomic nervous system. This treatment does not provide protection against CNS cholinergic overactivation and therefore convulsions require additional medication. Benzodiazepines are the currently accepted treatment for OP-induced convulsions, but the convulsions become refractory to these GABAA agonists and repeated dosing has diminishing effectiveness. As such, adjunct anticonvulsant treatments are needed to provide improved protection against recurrent and prolonged convulsions and the associated excitotoxic CNS damage that results from them. Previously we have shown that brief, 4-min administration of 3%–5% isoflurane in 100% oxygen has profound anticonvulsant and CNS protective effects when administered 30 min after a lethal dose of paraoxon. In this report we provide an extended time course of the effectiveness of 5% isoflurane delivered for 5 min, ranging from 60 to 180 min after a lethal dose of paraoxon in rats. We observed substantial effectiveness in preventing neuronal loss as shown by Fluoro-Jade B staining when isoflurane was administered 1 h after paraoxon, with diminishing effectiveness at 90, 120 and 180 min. In vivo magnetic resonance imaging (MRI) derived T2 and mean diffusivity (MD) values showed that 5-min isoflurane administration at a concentration of 5% prevents brain edema and tissue damage when administered 1 h after a lethal dose of paraoxon. We also observed reduced astrogliosis as shown by GFAP immunohistochemistry. Studies with continuous EEG monitoring are ongoing to demonstrate effectiveness in animal models of soman poisoning. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) are at risk of a many of central nervous system complications such as stroke and cognitive impairment. Studies based on diffusion tensor imaging (DTI) confirmed that the integrity of white matter in CKD patients has changed and these alterations can be observed before tissue morphological changes occurring on conventional MRI. Early use of DTI in CKD patients can distinguish early individuals with normal cognitive system function and will develop cognitive impairment in later stages. Results: As compared with controls, patients with CKD showed increased MD and decreased FA values in different brain regions with frontal, parietal regions and genu of corpus callosum more affected more than the occipital regions. For combined FA and MD in differentiating cases with CKD, there was statistically significant difference in both thalami, internal capsule, CC, cingulum, ILF and CST as p value < 0.05. Conclusions: DTI with fiber tractography can present the mainstay of imaging in evaluating the white matter integrity in CKD patient has normal conventional MRI with better diagnostic accuracy in differentiation between healthy and altered white matters. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential of 3 T magnetic resonance diffusion kurtosis imaging (DKI) in assessing the renal damage in early-stage of chronic kidney disease (CKD) patients with normal or slightly changed functional index, using histopathology as reference standard. Methods: 49 CKD patients and 18 healthy volunteers were recruited in this study. CKD patients were divided into two groups based on estimated glomerular filtration rate (eGFR): Study group I (eGFR ≥ 90 ml/min/1.73 m2 [n = 20]) and Study group II (eGFR < 90 ml/min/1.73 m2 [n = 29]). DKI was performed in all participants. The DKI parameters (mean kurtosis [MK], mean diffusivity [MD], fractional anisotropy [FA]) of renal cortex and medulla were measured. The differences of parenchymal MD, MK and FA values among the different groups were compared. The correlations between DKI parameters and clinicopathological characteristics were assessed. Diagnostic performance of DKI to assess renal damage in early-stage of CKD was analyzed. Results: The cortex MD and MK showed significant difference among three groups (P < 0.05): trend of cortex MD: Study group II < Study group I < control group; trend of cortex MK: control group < Study group I < Study group II. The cortex MD and MK and medulla FA were correlated with eGFR and Interstitial fibrosis/Tubular atrophy score (0.3 < r < 0.5). Cortex MD and MK yielded an AUC of 0.752 for differentiating healthy volunteers from CKD patients with eGFR ≥ 90 ml/min/1.73 m2. Conclusion: DKI shows potential in non-invasive and multi-parameter quantitative assessment of renal damage in early-stage of CKD patients and provide additional information for changes in renal function and histopathology. [ABSTRACT FROM AUTHOR]

Neuroimaging signatures based on composite scores of cortical thickness and hippocampal volume predict progression from mild cognitive impairment to Alzheimer's disease. However, little is known about the ability of these signatures among cognitively normal adults to predict progression to mild cognitive impairment. Towards that end, a signature sensitive to microstructural changes that may predate macrostructural atrophy should be useful. We hypothesized that: (i) a validated MRI-derived Alzheimer's disease signature based on cortical thickness and hippocampal volume in cognitively normal middle-aged adults would predict progression to mild cognitive impairment; and (ii) a novel grey matter mean diffusivity signature would be a better predictor than the thickness/volume signature. This cohort study was part of the Vietnam Era Twin Study of Aging. Concurrent analyses compared cognitively normal and mild cognitive impairment groups at each of three study waves (ns = 246-367). Predictive analyses included 169 cognitively normal men at baseline (age = 56.1, range = 51-60). Our previously published thickness/volume signature derived from independent data, a novel mean diffusivity signature using the same regions and weights as the thickness/volume signature, age, and an Alzheimer's disease polygenic risk score were used to predict incident mild cognitive impairment an average of 12 years after baseline (follow-up age = 67.2, range = 61-71). Additional analyses adjusted for predicted brain age difference scores (chronological age minus predicted brain age) to determine if signatures were Alzheimer-related and not simply ageing-related. In concurrent analyses, individuals with mild cognitive impairment had higher (worse) mean diffusivity signature scores than cognitively normal participants, but thickness/volume signature scores did not differ between groups. In predictive analyses, age and polygenic risk score yielded an area under the curve of 0.74 (sensitivity = 80.00%; specificity = 65.10%). Prediction was significantly improved with addition of the mean diffusivity signature (area under the curve = 0.83; sensitivity = 85.00%; specificity = 77.85%; P = 0.007), but not with addition of the thickness/volume signature. A model including both signatures did not improve prediction over a model with only the mean diffusivity signature. Results held up after adjusting for predicted brain age difference scores. The novel mean diffusivity signature was limited by being yoked to the thickness/volume signature weightings. An independently derived mean diffusivity signature may thus provide even stronger prediction. The young age of the sample at baseline is particularly notable. Given that the brain signatures were examined when participants were only in their 50 s, our results suggest a promising step towards improving very early identification of Alzheimer's disease risk and the potential value of mean diffusivity and/or multimodal brain signatures.

Abstract Background Low back pain (LBP) is one of the most common musculoskeletal complaints and considered as the most disabling condition among general population. Magnetic resonance imaging (MRI) is the preferred modality in imaging of LBP. Diffusion tensor imaging (DTI) is a version of MRI that can detect tissue microstructure changes occurring in different pathologies. The commonly used parameters are fractional anisotropy (FA) and mean diffusivity (MD). We aimed in this study to evaluate the role of DTI in the assessment of back muscles in young adults with chronic LBP with no major neurological or orthopedic disorders. Results There was a statistically significant difference in MD values of back muscles between patients and control groups. At the ROC curve, for psoas muscle, the AUC was 0.906 with a cutoff point of 0.951. Sensitivity and specificity were 89.2% and 90.9% with accuracy 89.8%. For multifidus muscle, the AUC was 0.919 with a cutoff point of 1.29. Sensitivity and specificity were 91.9% and 90.9% with accuracy 91.4%. For erector spinae muscle, the AUC was 0.834 with a cutoff point of 1.224. Sensitivity and specificity were 81.1% and 72.7% with accuracy 77.9%. There was a statistically significant difference in FA values of back muscles between the patients and control groups. At the ROC curve, for psoas muscle, the AUC was 0.840 with a cutoff point of 0.546. Sensitivity and specificity were 81.1% and 72.7% with accuracy 77.97%. For multifidus muscle, the AUC was 0.875 with a cutoff point of 0.415. Sensitivity and specificity were 81.1% and 90.9% with accuracy 84.7%. For erector spinae muscle, the AUC was 0.805 with a cutoff point of 0.437. Sensitivity and specificity were 81.1% and 77.3% with accuracy 79.7%. Conclusions DTI is a valuable promising noninvasive tool in the assessment of back muscles quality in patient with chronic low back pain, with no detected neurological or orthopedic pathologies. This is due to its sensitivity to microscopic intracellular changes that could not be detected on conventional imaging, allowing better tissue characterization.

Purpose: To quantitatively investigate the microstructural properties of the optic nerve (ON) in vivo using diffusion magnetic resonance imaging (dMRI) tractography in an elderly population and to determine the differences between the ON diffusion properties stratified by basic demographics. Methods: We measured fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of the intraorbital ON in cognitively normal controls selected from the Alzheimer's Disease Neuroimaging Initiative 3 database (n =104; mean age = 73. 8 ± 8.1 years) using dMRI probabilistic tractography and evaluated the correlation between diffusion parameters and demographic factors. Diffusion parameters were measured in 20 equidistant nodes along the tract, and the data from proximal 70% (14 nodes) of the intraorbital ON were averaged. Results: The mean FA of the intraorbital ON was 0.392 ± 0.063, and the mean MD was 1.163 ± 0.165 μm2/s. The mean RD was 0.882 ± 0.152 μm2/s, and the mean AD was 1.693 ± 0.183 μm2/s. The multiple linear regression model showed a negative correlation between FA and age. FA in females was significantly higher than males, whereas RD in female was significantly lower. Conclusions: We measured the diffusion properties of the intraorbital ON using dMRI tractography in an elderly cognitively normal population. The diffusion properties detected by dMRI tractography may substantially reflect the microstructure of the ON.

Diffusion imaging is very useful for the diagnosis of sporadic Creutzfeldt-Jakob disease, but it has limitations in tracking disease progression as mean diffusivity changes non-linearly across the disease course. We previously showed that mean diffusivity changes across the disease course follow a quasi J-shaped curve, characterized by decreased values in earlier phases and increasing values later in the disease course. Understanding how MRI metrics change over-time, as well as their correlations with clinical deficits are crucial steps in developing radiological biomarkers for trials. Specifically, as mean diffusivity does not change linearly and atrophy mainly occurs in later stages, neither alone is likely to be a sufficient biomarker throughout the disease course. We therefore developed a model combining mean diffusivity and Volume loss (MRI Disease-Staging) to take into account mean diffusivity's non-linearity. We then assessed the associations between clinical outcomes and mean diffusivity alone, Volume alone and finally MRI Disease-Staging. In 37 sporadic Creutzfeldt-Jakob disease subjects and 30 age- and sex-matched healthy controls, high angular resolution diffusion and high-resolution T1 imaging was performed cross-sectionally to compute z-scores for mean diffusivity (MD) and Volume. Average MD and Volume were extracted from 41 GM volume of interest (VOI) per hemisphere, within the images registered to the Montreal Neurological Institute (MNI) space. Each subject's volume of interest was classified as either "involved" or "not involved" using a statistical threshold of ± 2 standard deviation (SD) for mean diffusivity changes and/or -2 SD for Volume. Volumes of interest were MRI Disease-Staged as: 0 = no abnormalities; 1 = decreased mean diffusivity only; 2 = decreased mean diffusivity and Volume; 3 = normal ("pseudo-normalized") mean diffusivity, reduced Volume; 4 = increased mean diffusivity, reduced Volume. We correlated Volume, MD and MRI Disease-Staging with several clinical outcomes (scales, score and symptoms) using 4 major regions of interest (Total, Cortical, Subcortical and Cerebellar gray matter) or smaller regions pre-specified based on known neuroanatomical correlates. Volume and MD z-scores correlated inversely with each other in all four major ROIs (cortical, subcortical, cerebellar and total) highlighting that ROIs with lower Volumes had higher MD and vice-versa. Regarding correlations with symptoms and scores, higher MD correlated with worse Mini-Mental State Examination and Barthel scores in cortical and cerebellar gray matter, but subjects with cortical sensory deficits showed lower MD in the primary sensory cortex. Volume loss correlated with lower Mini-Mental State Examination, Barthel scores and pyramidal signs. Interestingly, for both Volume and MD, changes within the cerebellar ROI showed strong correlations with both MMSE and Barthel. Supporting using a combination of MD and Volume to track sCJD progression, MRI Disease-Staging showed correlations with more clinical outcomes than Volume or MD alone, specifically with Mini-Mental State Examination, Barthel score, pyramidal signs, higher cortical sensory deficits, as well as executive and visual-spatial deficits. Additionally, when subjects in the cohort were subdivided into tertiles based on their Barthel scores and their percentile of disease duration/course ("Time-Ratio"), subjects in the lowest (most impaired) Barthel tertile showed a much greater proportion of more advanced MRI Disease-Stages than the those in the highest tertile. Similarly, subjects in the last Time-Ratio tertile (last tertile of disease) showed a much greater proportion of more advanced MRI Disease-Stages than the earliest tertile. Therefore, in later disease stages, as measured by time or Barthel, there is overall more Volume loss and increasing MD. A combined multiparametric quantitative MRI Disease-Staging is a useful tool to track sporadic Creutzfeldt-Jakob- disease progression radiologically.

Organophosphate-based chemical agents (OP), including nerve agents and certain pesticides such as paraoxon, are potent acetylcholinesterase inhibitors that cause severe convulsions and seizures, leading to permanent central nervous system (CNS) damage if not treated promptly. The current treatment regimen for OP poisoning is intramuscular injection of atropine sulfate with an oxime such as pralidoxime (2-PAM) to mitigate cholinergic over-activation of the somatic musculature and autonomic nervous system. This treatment does not provide protection against CNS cholinergic overactivation and therefore convulsions require additional medication. Benzodiazepines are the currently accepted treatment for OP-induced convulsions, but the convulsions become refractory to these GABAA agonists and repeated dosing has diminishing effectiveness. As such, adjunct anticonvulsant treatments are needed to provide improved protection against recurrent and prolonged convulsions and the associated excitotoxic CNS damage that results from them. Previously we have shown that brief, 4-min administration of 3%-5% isoflurane in 100% oxygen has profound anticonvulsant and CNS protective effects when administered 30 min after a lethal dose of paraoxon. In this report we provide an extended time course of the effectiveness of 5% isoflurane delivered for 5 min, ranging from 60 to 180 min after a lethal dose of paraoxon in rats. We observed substantial effectiveness in preventing neuronal loss as shown by Fluoro-Jade B staining when isoflurane was administered 1 h after paraoxon, with diminishing effectiveness at 90, 120 and 180 min. In vivo magnetic resonance imaging (MRI) derived T2 and mean diffusivity (MD) values showed that 5-min isoflurane administration at a concentration of 5% prevents brain edema and tissue damage when administered 1 h after a lethal dose of paraoxon. We also observed reduced astrogliosis as shown by GFAP immunohistochemistry. Studies with continuous EEG monitoring are ongoing to demonstrate effectiveness in animal models of soman poisoning. [ABSTRACT FROM AUTHOR]

BACKGROUND:There is histological evidence of microstructural changes in the zygomaticotemporal branch of the trigeminal nerve in migraineurs. This raises the possibility that altered trigeminal nerve properties contribute to migraine pathophysiology. Whilst it is not possible to explore the anatomy of small trigeminal nerve branches it is possible to explore the anatomy of the trigeminal root entry zone using magnetic resonance imaging in humans. The aim of this investigation is to assess the microstructure of the trigeminal nerve in vivo to determine if nerve alterations occur in individuals with episodic migraine. METHODS:In 39 migraineurs and 39 matched controls, T1-weighted anatomical images were used to calculate the volume (mm3) and maximal cross-sectional area of the trigeminal nerve root entry zone; diffusion tensor images were used to calculate fractional anisotropy, mean diffusion, axial diffusion and radial diffusion. RESULTS:There were significant differences between the left and right nerve of controls and migraineurs with respect to volume and not cross-sectional area. Migraineurs displayed reduced axial diffusion in the right nerve compared to the left nerve, and reduced fractional anisotropy in the left nerve compared to left controls. Furthermore, although there were no differences in mean diffusion or radial diffusion, regional analysis of the nerve revealed significantly greater radial diffusion in the middle and rostral portion of the left trigeminal nerve in migraineurs compared with controls. CONCLUSIONS:Migraine pathophysiology is associated with microstructural abnormalities within the trigeminal nerve that are consistent with histological evidence of altered myelin and/or organization. These peripheral nerve changes may provide further insight into migraine pathophysiology and enable a greater understanding for targeted treatments of pain alleviation.

Abstract Objective High‐resolution (1 mm isotropic) diffusion tensor imaging (DTI) of the hippocampus in temporal lobe epilepsy (TLE) patients has shown patterns of hippocampal subfield diffusion abnormalities, which were consistent with hippocampal sclerosis (HS) subtype on surgical histology. The objectives of this longitudinal imaging study were to determine the stability of focal hippocampus diffusion changes over time in TLE patients, compare diffusion and quantitative T2 abnormalities of the sclerotic hippocampus, and correlate presurgical mean diffusivity (MD) and T2 maps with postsurgical histology. Methods Nineteen TLE patients and 19 controls underwent two high‐resolution (1 mm isotropic) DTI and 1.1 × 1.1 × 1 mm3 T2 relaxometry scans (in a subset of 16 TLE patients and 9 controls) of the hippocampus at 3T, with a 2.6 ± 0.8 year inter‐scan interval. Within‐participant hippocampal volume, MD and T2 were compared between the scans. Contralateral hippocampal changes 2.3 ± 1.0 years after surgery and ipsilateral preoperative MD maps versus postoperative subfield histopathology were evaluated in eight patients who underwent surgical resection of the hippocampus. Results Reduced volume and elevated MD and T2 of sclerotic hippocampi remained unchanged between longitudinal scans. Focal regions of elevated MD and T2 in bilateral hippocampi of HS TLE were detected consistently at both scans. Regions of high MD and T2 correlated and remained consistent over time. Volume, MD, and T2 remained unchanged in postoperative contralateral hippocampus. Regional elevations of MD identified subfield neuron loss on postsurgical histology with 88% sensitivity and 88% specificity. Focal T2 elevations identified subfield neuron loss with 75% sensitivity and 88% specificity. Significance Diffusion and T2 abnormalities in ipsilateral and contralateral hippocampi remained unchanged between the scans suggesting permanent microstructural alterations. MD and T2 demonstrated good sensitivity and specificity to detect hippocampal subfield neuron loss on postsurgical histology, supporting the potential that high‐resolution hippocampal DTI and T2 could be used to diagnose HS subtype before surgery.

Abstract Background Cortical and subcortical microstructural modifications are critical to understanding the pathogenic changes in frontotemporal lobar degeneration (FTLD) subtypes. In this study, we investigated cortical and subcortical microstructure underlying cognitive and language impairments across behavioral variant of frontotemporal dementia (bvFTD), semantic variant of primary progressive aphasia (svPPA), and nonfluent variant of primary progressive aphasia (nfvPPA) subtypes. Methods The current study characterized 170 individuals with 3 T MRI structural and diffusion-weighted imaging sequences as portion of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study: 41 bvFTD, 35 nfvPPA, 34 svPPA, and 60 age-matched cognitively unimpaired controls. To determine the severity of the disease, clinical dementia rating plus national Alzheimer’s coordinating center behavior and language domains sum of boxes scores were used; other clinical measures, including the Boston naming test and verbal fluency test, were also evaluated. We computed surface-based cortical thickness and cortical and subcortical microstructural metrics using tract-based spatial statistics and explored their relationships with clinical and cognitive assessments. Results Compared with controls, those with FTLD showed substantial cortical mean diffusivity alterations extending outside the regions with cortical thinning. Tract-based spatial statistics revealed that anomalies in subcortical white matter diffusion were widely distributed across the frontotemporal and parietal areas. Patients with bvFTD, nfvPPA, and svPPA exhibited distinct patterns of cortical and subcortical microstructural abnormalities, which appeared to correlate with disease severity, and separate dimensions of language functions. Conclusions Our findings imply that cortical and subcortical microstructures may serve as sensitive biomarkers for the investigation of neurodegeneration-associated microstructural alterations in FTLD subtypes. Graphical Abstract Flowchart of the study design (see materials and methods for detailed description).

Abstract Background Epilepsy is a common neurological disorder especially in pediatric population. Patients with non-lesional epilepsy have normal conventional MRI findings. In the recent era of advances in neuroimaging studies, diffusion tensor imaging (DTI) and MR spectroscopy (MRS) can assess the tissue microstructure. Also, arterial spin labeling (ASL) is a noninvasive modality that evaluates cerebral blood flow. Multiple recent publications aimed at use of single or two new modalities in lateralization of epileptogenic focus in epilepsy, but the current study aimed to evaluate the added value of combined (DTI, ASL and MRS) in vivo localization of interactable epilepsy with negative conventional MRI findings. Results This prospective case control study was carried out in the period from January 1st, 2022 to October 1st, 2022 after approval of local ethical committee in our institution. Written informed consent was obtained from patients and healthy volunteers who were enrolled in this study. The current study included 46 patients with temporal lobe epilepsy and 20 age- and sex-matched healthy volunteers as a control group. The mean age in the patient group was 22.3 ± 12.2 years, and in the control group, it was 23.8 ± 15.1 years. The highest area under the curve (AUC) was for spectroscopy (0.913), the difference in NAA/Cr showed sensitivity of 94.1% and a specificity of 90%, while NAA/Cho + Cr showed a sensitivity of 91.8% and a specificity of 88%, the difference in rCBF showed an AUC of 0.89, with a cutoff value of 3.815 had a sensitivity of 80.4% and a specificity of 85%. As regards DTI, the changes in DTI parameters show sensitivity of 79.6% and a specificity of 80% in lateralization of the epileptic focus. The difference in FA only showed an AUC of 0.86, with a cutoff value of 0.01 had a sensitivity of 77% and a specificity of 75% and the difference in MD only showed an AUC of 0.771, with a cutoff value of 0.545 had a sensitivity of 67.4% and a specificity of 70%. The diagnostic performance of MRS in terms of the AUC was significantly higher than ASL parameters (difference in NAA/Cr, p = 0.033 and difference in NAA/Cho + Cr, p = 0.044), and MD (p = 0.02). No other statistically significant differences were shown between the studied parameters. When the three methods were combined, all patients’ epileptogenic foci were correctly localized and lateralized. Conclusions Combining ASL, DTI and H-MRS provided excellent diagnostic performance in localization and lateralization of the epileptogenic focus. If this combination is not applicable in clinical practice, ASL could provide a considerably accurate and feasible method in this context. The present study supported the value of the new noninvasive MRI techniques in the elaboration of hidden brain pathology.

Background: Although changes in diffusion characteristics of the brain parenchyma in neurological disorders are widely studied and used in clinical practice, the change in diffusivity in the cerebrospinal fluid (CSF) system is rarely reported. In this study, free water diffusion in the subarachnoid cisterns and ventricles of the rat brain was examined using diffusion magnetic resonance imaging (MRI), and the effects of neurological disorders on diffusivity in CSF system were investigated. Methods: Diffusion MRI and T2-weighted images were obtained in the intact rats, 24 h after ischemic stroke, and 50 days after mild traumatic brain injury (mTBI). We conducted the assessment of diffusivity in the rat brain in the subarachnoid cisterns around the midbrain, as well as the lateral ventricles. One-way ANOVA and Kruskal–Wallis test were used to evaluate the change in mean diffusivity (MD) and MD histogram, respectively, in CSF system following different neurological disease. Results: A significant decrease in the mean MD value of the subarachnoid cisterns was observed in the stroke rats compared with the intact and mTBI rats (p

Advanced neuroimaging techniques show promise as a biomarker for mild traumatic brain injury (mTBI). However, little research has evaluated cerebral hemodynamics or its relation to white matter microstructure post-mTBI in children. This novel pilot study examined differences in cerebral hemodynamics, as measured using functional near-infrared spectroscopy (fNIRS), and its association with diffusion tensor imaging (DTI) metrics in children with mTBI or mild orthopedic injury (OI) to address these gaps. Children 8.00?16.99 years of age with mTBI (n?=?9) or OI (n?=?6) were recruited in a pediatric emergency department, where acute injury characteristics were assessed. Participants completed DTI twice, post-acutely (2?33 days) and chronically (3 or 6 months), and fNIRS ?1 month post-injury. Automated deterministic tractography was used to compute DTI metrics. There was reduced absolute phase globally and coherence in the dorsolateral pre-frontal cortex (DLPFC) after mTBI compared to the OI group. Coherence in the DLPFC and absolute phase globally showed distinct associations with fractional anisotropy in interhemispheric white matter pathways. Two fNIRS metrics (coherence and absolute phase) differentiated mTBI from OI in children. Variability in cerebral hemodynamics related to white matter microstructure. The results provide initial evidence that fNIRS may have utility as a clinical biomarker of pediatric mTBI.

Organophosphate-based chemical agents (OP), including nerve agents and certain pesticides such as paraoxon, are potent acetylcholinesterase inhibitors that cause severe convulsions and seizures, leading to permanent central nervous system (CNS) damage if not treated promptly. The current treatment regimen for OP poisoning is intramuscular injection of atropine sulfate with an oxime such as pralidoxime (2-PAM) to mitigate cholinergic over-activation of the somatic musculature and autonomic nervous system. This treatment does not provide protection against CNS cholinergic overactivation and therefore convulsions require additional medication. Benzodiazepines are the currently accepted treatment for OP-induced convulsions, but the convulsions become refractory to these GABAA agonists and repeated dosing has diminishing effectiveness. As such, adjunct anticonvulsant treatments are needed to provide improved protection against recurrent and prolonged convulsions and the associated excitotoxic CNS damage that results from them. Previously we have shown that brief, 4-min administration of 3%–5% isoflurane in 100% oxygen has profound anticonvulsant and CNS protective effects when administered 30 min after a lethal dose of paraoxon. In this report we provide an extended time course of the effectiveness of 5% isoflurane delivered for 5 min, ranging from 60 to 180 min after a lethal dose of paraoxon in rats. We observed substantial effectiveness in preventing neuronal loss as shown by Fluoro-Jade B staining when isoflurane was administered 1 h after paraoxon, with diminishing effectiveness at 90, 120 and 180 min. In vivo magnetic resonance imaging (MRI) derived T2 and mean diffusivity (MD) values showed that 5-min isoflurane administration at a concentration of 5% prevents brain edema and tissue damage when administered 1 h after a lethal dose of paraoxon. We also observed reduced astrogliosis as shown by GFAP immunohistochemistry. Studies with continuous EEG monitoring are ongoing to demonstrate effectiveness in animal models of soman poisoning.

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51–60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes. [ABSTRACT FROM AUTHOR]

Microdissection testicular sperm extraction (mTESE) is the first-line treatment plan for nonobstructive azoospermia (NOA). However, studies reported that the overall sperm retrieval rate (SRR) was 43% to 63% among men with NOA, implying that nearly half of the patients fail sperm retrieval. This study aimed to evaluate the diagnostic performance of parameters derived from diffusion tensor imaging (DTI) in predicting SRR in patients with NOA. Seventy patients diagnosed with NOA were enrolled and classified into two groups based on the outcome of sperm retrieval during mTESE: success (29 patients) and failure (41 patients). Scrotal magnetic resonance imaging was performed, and the DTI parameters, including mean diffusivity and fractional anisotropy, were analyzed between groups. The results showed that there was a significant difference in mean diffusivity values between the two groups, and the area under the curve for mean diffusivity was calculated as 0.865, with a sensitivity of 72.2% and a specificity of 97.5%. No statistically significant difference was observed in fractional anisotropy values and sex hormone levels between the two groups. This study demonstrated that the mean diffusivity value might serve as a useful noninvasive imaging marker for predicting the SRR of NOA patients undergoing mTESE. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is one of the most common musculoskeletal complaints and considered as the most disabling condition among general population. Magnetic resonance imaging (MRI) is the preferred modality in imaging of LBP. Diffusion tensor imaging (DTI) is a version of MRI that can detect tissue microstructure changes occurring in different pathologies. The commonly used parameters are fractional anisotropy (FA) and mean diffusivity (MD). We aimed in this study to evaluate the role of DTI in the assessment of back muscles in young adults with chronic LBP with no major neurological or orthopedic disorders. Results: There was a statistically significant difference in MD values of back muscles between patients and control groups. At the ROC curve, for psoas muscle, the AUC was 0.906 with a cutoff point of 0.951. Sensitivity and specificity were 89.2% and 90.9% with accuracy 89.8%. For multifidus muscle, the AUC was 0.919 with a cutoff point of 1.29. Sensitivity and specificity were 91.9% and 90.9% with accuracy 91.4%. For erector spinae muscle, the AUC was 0.834 with a cutoff point of 1.224. Sensitivity and specificity were 81.1% and 72.7% with accuracy 77.9%. There was a statistically significant difference in FA values of back muscles between the patients and control groups. At the ROC curve, for psoas muscle, the AUC was 0.840 with a cutoff point of 0.546. Sensitivity and specificity were 81.1% and 72.7% with accuracy 77.97%. For multifidus muscle, the AUC was 0.875 with a cutoff point of 0.415. Sensitivity and specificity were 81.1% and 90.9% with accuracy 84.7%. For erector spinae muscle, the AUC was 0.805 with a cutoff point of 0.437. Sensitivity and specificity were 81.1% and 77.3% with accuracy 79.7%. Conclusions: DTI is a valuable promising noninvasive tool in the assessment of back muscles quality in patient with chronic low back pain, with no detected neurological or orthopedic pathologies. This is due to its sensitivity to microscopic intracellular changes that could not be detected on conventional imaging, allowing better tissue characterization. [ABSTRACT FROM AUTHOR]

Objectives Age-related cognitive changes can be influenced by both brain maintenance (BM), which refers to the relative absence over time of changes in neural resources or neuropathologic changes, and cognitive reserve (CR), which encompasses brain processes that allow for better-than-expected behavioral performance given the degree of life-course-related brain changes. This study evaluated the effects of age, BM, and CR on longitudinal changes over 2 visits, 5 years apart, in 3 cognitive abilities that capture most of age-related variability. Methods Participants included 254 healthy adults aged 20–80 years at recruitment. Potential BM was estimated using whole-brain cortical thickness and white matter mean diffusivity at both visits. Education and intelligence quotient (IQ; estimated with American National Adult Reading Test) were tested as moderating factors for cognitive changes in the 3 cognitive abilities. Results Consistent with BM—after accounting for age, sex, and baseline performance—individual differences in the preservation of mean diffusivity and cortical thickness were independently associated with relative preservation in the 3 abilities. Consistent with CR—after accounting for age, sex, baseline performance, and structural brain changes—higher IQ, but not education, was associated with reduced 5-year decline in reasoning (β = 0.387, p =.002), and education was associated with reduced decline in speed (β = 0.237, p =.039). Discussion These results demonstrate that both CR and BM can moderate cognitive changes in healthy aging and that the 2 mechanisms can make differential contributions to preserved cognition. [ABSTRACT FROM AUTHOR]

Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse. We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability. CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models. As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability. While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation. Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608. • Psychomotor disturbance (PMD) is common in psychotic depression. • PMD is associated with relapse in this patient group. • We examined whether white matter microstructure (WM) explains this relationship. • Both PMD and WM were associated with relapse in our study group. • However, WM did not account for the relationship between PMD and relapse. [ABSTRACT FROM AUTHOR]

Having a first-degree relative with bipolar I disorder (BD) in conjunction with prodromal attention deficit/hyperactivity disorder (ADHD) may represent a unique phenotype that confers greater risk for developing BD than ADHD alone. However, underlying neuropathoetiological mechanisms remain poorly understood. This cross-sectional study compared regional microstructure in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC). A total of 140 (high-risk, n = 44; low-risk, n = 49; and HC, n = 47) youth (mean age: 14.1 ± 2.5 years, 65 % male) were included in the analysis. Diffusion tensor images were collected and fractional anisotropy (FA) and mean diffusivity (MD) maps were calculated. Both tract-based and voxel-based analyses were performed. Correlations between clinical ratings and microstructural metrics that differed among groups were examined. No significant group differences in major long-distance fiber tracts were observed. The high-risk ADHD group exhibited predominantly higher FA and lower MD in frontal, limbic, and striatal subregions compared with the low-risk ADHD group. Both low-risk and high-risk ADHD groups exhibited higher FA in unique and overlapping regions compared with HC subjects. Significant correlations between regional microstructural metrics and clinical ratings were observed in ADHD groups. Prospective longitudinal studies will be required to determine the relevance of these findings to BD risk progression. Psychostimulant-free ADHD youth with a BD family history exhibit different microstructure alterations in frontal, limbic, and striatal regions compared with ADHD youth without a BD family history, and may therefore represent a unique phenotype relevant to BD risk progression. • High-risk ADHD exhibit different regional microstructural abnormalities compared with low-risk ADHD. • Low- and high-risk groups exhibited unique and overlapping microstructural abnormalities compared with healthy controls. • Significant correlations with clinical scores were detected in ADHD groups. [ABSTRACT FROM AUTHOR]

We evaluated white matter microstructure integrity in perinatally HIV-infected (PHIV) youths receiving cART compared to age- and gender-matched healthy youths through DTI metrics using voxel-based morphometry (VBM). We investigated 14 perinatally HIV-infected patients (age 17.9 ± 2.5 years) on cART and 17 healthy youths (HC) (age 18.0 ± 3.0 years) using a 3T MRI scanner. Four DTI-derived metrics were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Statistical analysis was done with voxel-based analysis of covariance (ANCOVA), with age and gender as covariates. Region-of-interest secondary analyses in statistically significant regions were also performed. Regional increases in FA in the PHIV youths were found in left middle frontal gyrus, right precuneus, right lingual gyrus, and left supramarginal gyrus. Increased MD was found in the right precentral gyrus while decreased MD was found in the white matter of the right superior parietal lobule and right inferior temporal gyrus/fusiform gyrus. Regions of increased/decreased RD overlapped with regions of increased/decreased MD. Both increased and decreased AD were found in three to four regions respectively. The regional FA, MD, RD, and AD values were consistent with the voxel-based analysis findings. The findings are mostly consistent with previous literature, but increased FA has not been previously reported for perinatally HIV-infected youths. Potentially early and prolonged therapy in our population may have contributed to this new finding. Both toxicity of antiretroviral therapy and indolent infection must be considered as causative factors in the DTI metric changes that we have observed.

Recent research found that the combination of masculine gender identity and gynephilia was associated with cortical T1 relaxation time, which is considered to reflect gray matter density. We hypothesized that mean diffusivity (MD), a diffusion tensor imaging metric that reflects the degree to which water movement is free versus constrained, in combination with T1 relaxation time would provide further insight regarding cortical tissue characteristics. MD and T1 relaxation time were measured in 76 cortical regions in 15 adolescents assigned female at birth who experience gender dysphoria (GD AFAB) and were not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12–17 years). Sexual orientation was represented by the degree of androphilia–gynephilia and the strength of sexual attraction. In multivariate analyses, cortical T1 relaxation time showed a weak but statistically significant positive association with MD across the cortex, suggesting that macromolecule-rich cortical tissue also tends to show water movement that is somewhat more constrained. In further multivariate analyses, in several left frontal, parietal, and temporal regions, the combination of shorter T1 relaxation time and faster MD was associated with older age and greater gynephilia in GD AFAB individuals and cisgender boys and with stronger attractions in cisgender boys only. Thus, for these cortical regions in these groups, older age, gynephilia, and stronger attractions (cisgender boys only) were associated with macromolecule-rich tissue in which water movement was freer—a pattern that some prior research suggests is associated with greater cell density and size. Overall, this study indicates that investigating T1 relaxation time and MD together can further inform how cortical gray matter tissue characteristics relate to age and psychosexuality. [ABSTRACT FROM AUTHOR]