Lower Fractional Anisotropy Values Research Articles

Multimodal neural correlates of dispositional resilience among healthy individuals

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience’s neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.

Impacts of dioxin exposure on brain connectivity estimated by DTI analysis of MRI images in men residing in contaminated areas of Vietnam.

Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam. In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates. The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels. It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders.

Wallerian Degeneration Assessed by Multi-Modal Magnetic Resonance Imaging of Cervical Spinal Cord Is Associated With Neurological Impairment After Spinal Cord Injury.

While Wallerian degeneration (WD) is a crucial pathological process induced with spinal cord injury (SCI), its underlying mechanisms is still understudied. In this study, we aim to assess structural alterations and clinical significance of WD in the cervical cord following SCI using multi-modal magnetic resonance imaging (MRI), which combines T2*-weighted imaging and diffusion tensor imaging (DTI). T2*-weighted images allow segmentation of anatomical structures and the detection of WD on macrostructural level. DTI, on the other hand, can identify the reduction in neuroaxonal integrity by measuring the diffusion of water molecules on the microstructural level. In this prospective study, 35 SCI patients (19 paraplegic and 16 tetraplegic patients) and 12 healthy controls were recruited between July 2020 and May 2022. The hyperintensity voxels in the dorsal column was manually labeled as WD on T2*-weighted images. The mean cross-sectional area (CSA) and mean DTI indexes of WD at the C2 level were calculated and compared between groups. Correlation analysis was used to determine the associations of the magnitude of WD with lesion characteristics and clinical outcomes. Compared with controls, SCI patients showed evident hyperintensity (35/35) and decreased neuroaxonal integrity (p < 0.05) within the dorsal column at the C2 level. A higher neurological level of injury was associated with a larger mean CSA and reduction in neuroaxonal integrity within WD (p < 0.05). Smaller total and dorsal tissue bridges were related to greater mean CSA and lower fractional anisotropy values in WD (p < 0.05), respectively. Moreover, SCI participants with significantly larger CSAs and significantly lower microstructural integrity had worse sensory outcomes (p < 0.05). This comprehensive evaluation of WD can help us better understand the mechanisms of WD, monitor progression, and assess the effectiveness of therapeutic interventions after SCI.

Association of disruption of the right posterior arcuate fasciculus with spatial neglect.

Spatial neglect is a debilitating condition observed in patients with right-sided brain injuries in whom there is defective awareness of the contralesional space. Although classically considered a right parietal lobe deficit, there has been increasing interest in the specific white matter (WM) architecture subserving spatial neglect. Patients who have lesions associated with chronic disruptions in visuospatial networks are of significant relevance in elucidating the WM tracts associated with spatial attention. In this study, the authors used two independent analytical methods to examine the relationship between WM connectivity changes and spatial attention. Thirty patients with right-sided glioma underwent diffusion tensor imaging (DTI) tractography and neuropsychological testing prior to tumor resection. Spatial neglect was assessed using the Bells Test. Diffusion connectometry analysis was performed to calculate the probability of injury to 55 WM tracts. Next, quantitative DTI tractography was used to reconstruct 9 major WM tracts and obtain fractional anisotropy (FA) and streamline number values as indices of connectivity. Differences in connectivity were assessed between patients with neglect and controls. Of the WM tracts analyzed by diffusion connectometry, only the right posterior segment of the arcuate fasciculus (psAF) showed a higher probability of disconnection in patients with evidence of hemispatial neglect compared to tract reconstructions of previously published healthy controls (hemineglect: 42% ± 12.5%, vs control: 6.3% ± 4.8% [mean ± SEM]; p < 0.05). Of the WM tracts reconstructed by DTI tractography, only the right psAF demonstrated consistently lower indices of connectivity based on the mean streamline number (hemineglect: 550.35 ± 183.41, vs control: 1407.01 ± 319.93; p < 0.05) and FA value (hemineglect: 0.40 ± 0.013, vs control: 0.44 ± 0.0063; p < 0.05) in patients who demonstrated neglect compared to controls. The right long segment of the arcuate fasciculus, inferior frontooccipital fasciculus, and inferior longitudinal fasciculus also demonstrated a lower streamline number, but not a lower FA value, in patients with evidence of hemineglect. These findings suggest that parietotemporal networks mediated by the right psAF may play a critical role in visuospatial attention. This analysis may help to disentangle the organization of the visuospatial attention networks, predict deficits in patients with glioma, and optimize surgical planning.

Sleep disturbances, altered brain microstructure and chronic headache in youth.

Chronic headache (persistent or recurrent headache for 3-months or longer) is highly prevalent among youth. While sleep disturbances have been associated with headache, their inter-relationship with brain connectivity remains unknown. This observational study examined whether self-report and actigraphy measures of sleep were associated with alterations to white matter tracts (i.e., uncinate fasciculus and cingulum) in youth with chronic headache versus healthy controls. Thirty youth aged 10-18 years with chronic headache and thirty controls underwent an MRI. Diffusion tensor images were obtained and mean fractional anisotropy values of the cingulum and uncinate were extracted. One-week prior to their MRI, youth wore an actigraph to obtain sleep duration, wake after sleep onset and sleep efficiency measures. Moreover, they completed questionnaires regarding their sleep quality and pain symptomatology. Linear regression was applied to examine the relationships between sleep (self-report and actigraphy), fractional anisotropy, and number of headache days per month. Self-report and actigraphy measures of sleep did not differ between patients and controls. However, poorer self-reported sleep quality was associated with lower fractional anisotropy values in the left uncinate (P = 0.05). Lower left uncinate fractional anisotropy was related to increased headache frequency (P = 0.002) in youth with chronic headache. Therefore, alterations to connectivity may be associated with the relationship between altered perceptions of sleep and headache chronicity.

Microstructural abnormality of white matter tracts in rheumatoid arthritis

BackgroundStructural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. ObjectivesTo automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. MethodsThis single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. ResultsCompared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. ConclusionsWe report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

The relationship between blast-related mild traumatic brain injury and executive function is moderated by white matter integrity.

Blast-related mild traumatic brain injury (BR mTBI) is a critical research area in recent combat veterans due to increased prevalence of survived blasts. Post-BR mTBI outcomes are highly heterogeneous and defining neurological differences may help in discrimination and prediction of cognitive outcomes. This study investigates whether white matter integrity, measured with diffusion tensor imaging (DTI), could influence how remote BR mTBI history is associated with executive control. The sample included 151 Veterans from the Minneapolis Veterans Affairs Medical Center who were administered a clinical/TBI assessment, neuropsychological battery, and DTI scan as part of a larger battery. From previous research, six white matter tracts were identified as having a putative relationship with blast severity: the cingulum, hippocampal cingulum, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and uncinate. Fractional anisotropy (FA) of the a priori selected white matter tracts and report of BR mTBI were used as predictors of Trail-Making Test B (TMT-B) performance in a multiple linear regression model. Statistical analysis revealed that FA of the hippocampal cingulum moderated the association between report of at least one BR mTBI and poorer TMT-B performance (p < 0.008), such that lower FA value was associated with worse TMT-B outcomes in individuals with BR mTBI. No significant moderation existed for other selected tracts, and the effect was not observed with predictors aside from history of BR mTBI. Investigation at the individual-tract level may lead to a deeper understanding of neurological differences between blast-related and non-blast related injuries.

Large-scale investigation of white matter structural differences in bilingual and monolingual children: An adolescent brain cognitive development data study.

Emerging research has provided valuable insights into the structural characteristics of the bilingual brain from studies of bilingual adults; however, there is a dearth of evidence examining brain structural alterations in childhood associated with the bilingual experience. This study examined the associations between bilingualism and white matter organization in bilingual children compared to monolingual peers leveraging the large-scale data from the Adolescent Brain Cognitive Development (ABCD) Study. Then, 446 bilingual children (ages 9-10) were identified from the participants in the ABCD data and rigorously matched to a group of 446 monolingual peers. Multiple regression models for selected language and cognitive control white matter pathways were used to compare white matter fractional anisotropy (FA) values between bilinguals and monolinguals, controlling for demographic and environmental factors as covariates in the models. Results revealed significantly lower FA values in bilinguals compared to monolinguals across established dorsal and ventral language network pathways bilaterally (i.e., the superior longitudinal fasciculus and inferior frontal-occipital fasciculus) and right-hemispheric pathways in areas related to cognitive control and short-term memory (i.e., cingulum and parahippocampal cingulum). In contrast to the enhanced FA values observed in adult bilinguals relative to monolinguals, our findings of lower FA in bilingual children relative to monolinguals may suggest a protracted development of white matter pathways associated with language and cognitive control resulting from dual language learning in childhood. Further, these findings underscore the need for large-scale longitudinal investigation of white matter development in bilingual children to understand neuroplasticity associated with the bilingual experience during this period of heightened language learning.

Diffusion tensor imaging in pediatric patients with dystonia

Background: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia.Methods: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies.Results: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus.Conclusion: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

53 Does the Corpus Callosum Recover from Concussion? Longitudinal Evidence from a Diffusion Tensor Imaging Study

Objective:Given that at least 75% of traumatic brain injuries in the U.S. are mild, concussions are a serious public health concern that cause significant neurological damage and negatively impact individuals’ quality of life. Due to the rotational forces that occur during a concussion, immediate damage to the corpus callosum is common, resulting in neurological and behavioral deficits. However, the longitudinal damage to the integrity of the corpus callosum is unclear and may differ across sections of the corpus callosum. Our primary aim was to compare the white matter integrity across eight corpus callosum tracts in concussed individuals to healthy controls 3-4 weeks after injury and at a 10-month follow-up.Participants and Methods:Seventeen concussed participants completed a diffusion tensor imaging (DTI) scan 3-4 weeks after receiving a concussion and again 10 months after injury. Nineteen control participants completed a single DTI scan. DTI data were analyzed using the automated fiber quantification (AFQ) pipeline, which extracts fractional anisotropy (FA) values from 100 nodes in eight tracts of the corpus callosum (listed anterior to posterior): orbital frontal, anterior frontal, superior frontal, motor, superior parietal, posterior parietal, occipital, and temporal. Given the non-linearity, high multicollinearity, and large number of data points, a cubic smoothing spline was used to fit a penalized regression to the FA values in each tract, allowing us to compare the FA values of each node in each tract between groups and across time. To assess acute damage, a spline model for the concussed participants at 3-4 weeks was compared to a spline model for the control participants in each tract. To assess longitudinal damage, a spline model of the FA difference value (10-month minus acute visit) in concussed participants was compared to a spline model of the FA difference value for controls (zero, representative of a theoretical no change in FA values). Significant nodes were defined as p-values less than 0.006 (alpha of .05/8, given 8 tracts).Results:Acutely following injury, concussed participants showed lower FA values than controls in the anterior frontal, posterior parietal, occipital, and temporal tracts. In the orbital frontal tract, concussed participants had higher FA values on the left, but decreased FA values compared to controls in the middle. Longitudinally, concussed participants showed continued decreased white matter integrity in the orbital frontal, superior parietal, and occipital tracts, but improved white matter integrity in the anterior frontal and superior frontal tracts. The motor, posterior parietal, and temporal tracts showed mixed longitudinal results of decreased or improved white matter integrity within each tract.Conclusions:Concussed individuals show decreased white matter integrity across the corpus callosum acutely after injury. Longitudinally, the most anterior and posterior portions of the corpus callosum (i.e., genu and splenium) show continued damaged while the more medial sections of the corpus callosum may show some recovery. Results suggest the corpus callosum displays differential patterns of damage acutely and longitudinally following concussion, with some tracts improving while others continue to deteriorate.

Altered White Matter Structural Network Connectivity Associated with Cognitive Declines in Psychogenic Erectile Dysfunction.

It has been reported that individuals with psychogenic erectile dysfunction (pED) potentially suffer from cognitive declines. Despite that increasing neuroimaging studies have demonstrated abnormalities of cerebral structural changes in pED, the association between altered white matter (WM) structural network and cognitive impairments remains unclear. Hence, this study aimed to explore the relationship between WM structural network connectivity and cognitive performance in patients with pED. Forty pED patients and 33 healthy controls (HCs) were recruited to perform cognitive assessments, and diffusion tensor imaging scans. We firstly constructed the WM structural network and applied the machine learning method to identify the important features. Then, we examined group differences in cognitive assessments, WM structural network connectivity within the identified features, and associations between altered WM structural network connectivity and cognitive scores in pED patients. From 26,896 features of DTI data, 24 important features were identified by K-Nearest Neighbor classification with a satisfactory accuracy (78%). Compared with HCs, we found that pED patients showed higher fractional anisotropy (FA) values between left transverse temporal sulcus and left supramarginal gyrus, and lower FA values between left suborbital sulcus and left para-hippocampal part of the medial occipito-temporal gyrus in pED patients. Furthermore, the increased FA between left transverse temporal sulcus and left supramarginal gyrus was observed to be negatively associated with impaired delayed memory. Overall, our findings provide new insights into WM network alterations associated with impaired cognitive functions in pED, which may unravel the potential neural mechanisms underlying the cognitive impairments of pED patients.

Hypothalamic Injury and Clinical Outcomes in Patients with Post-Traumatic Hyponatremia: A Diffusion Tensor Imaging Case-Control Study.

BACKGROUND Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) method used to identify changes in microstructures in the brain's white matter. Severe brain injuries after trauma are associated with disorders of consciousness (DOC) and may result in hyponatremia due to damage to the hypothalamus. This case-control study aimed to use DTI to evaluate the hypothalamus in 36 patients with hyponatremia and DOC due to severe brain injuries. MATERIAL AND METHODS Thirty-six patients with DOC after traumatic brain injury (TBI) and 36 healthy control subjects were enrolled in this study. The diagnosis of DOC was based on the coma recovery scale-revised (CRS-R). The 36 patients were divided into 2 groups: Group A (18 with hyponatremia, serum sodium level <135 mmol/L) and group B (18 without hyponatremia). The DTI scans were conducted using a 6-channel head coil on a 1.5T Philips Gyroscan Intera scanner. Among the DTI data, fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the hypothalamus were analyzed. RESULTS Patient group A had a lower FA value (P=0.044) and higher ADC value (P=0.004) of the hypothalamus and showed a longer length of hospital stay (P=0.03), lower CRS-R score at discharge (P=0.01), and less change in CRS-R score (P=0.004) compared to patient group B. The improvements in the CRS-R score revealed a moderate negative correlation (r=-0.467) with the severity of the hyponatremia (P=0.004). CONCLUSIONS Post-traumatic hyponatremia was associated with hypothalamic injury and the presence and severity of hyponatremia were associated with poor clinical outcomes in DOC patients.

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate β values and 95% CI. After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (β -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend < .05), except for FA values in projection fibers. These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.

Use of Support Vector Machines Approach via ComBat Harmonized Diffusion Tensor Imaging for the Diagnosis and Prognosis of Mild Traumatic Brain Injury: A CENTER-TBI Study.

The prediction of functional outcome after mild traumatic brain injury (mTBI) is challenging. Conventional magnetic resonance imaging (MRI) does not do a good job of explaining the variance in outcome, as many patients with incomplete recovery will have normal-appearing clinical neuroimaging. More advanced quantitative techniques such as diffusion MRI (dMRI), can detect microstructural changes not otherwise visible, and so may offer a way to improve outcome prediction. In this study, we explore the potential of linear support vector classifiers (linearSVCs) to identify dMRI biomarkers that can predict recovery after mTBI. Simultaneously, the harmonization of fractional anisotropy (FA) and mean diffusivity (MD) via ComBat was evaluated and compared for the classification performances of the linearSVCs. We included dMRI scans of 179 mTBI patients and 85 controls from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a multi-center prospective cohort study, up to 21 days post-injury. Patients were dichotomized according to their Extended Glasgow Outcome Scale (GOSE) scores at 6 months into complete (n = 92; GOSE = 8) and incomplete (n = 87; GOSE <8) recovery. FA and MD maps were registered to a common space and harmonized via the ComBat algorithm. LinearSVCs were applied to distinguish: (1) mTBI patients from controls and (2) mTBI patients with complete from those with incomplete recovery. The linearSVCs were trained on (1) age and sex only, (2) non-harmonized, (3) two-category-harmonized ComBat, and (4) three-category-harmonized ComBat FA and MD images combined with age and sex. White matter FA and MD voxels and regions of interest (ROIs) within the John Hopkins University (JHU) atlas were examined. Recursive feature elimination was used to identify the 10% most discriminative voxels or the 10 most discriminative ROIs for each implementation. mTBI patients displayed significantly higher MD and lower FA values than controls for the discriminative voxels and ROIs. For the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD voxel-wise linearSVC provided significantly higher classification scores (81.4% accuracy, 93.3% sensitivity, 80.3% F1-score, and 0.88 area under the curve [AUC], p < 0.05) compared with the classification based on age and sex only and the ROI approaches (accuracies: 59.8% and 64.8%, respectively). Similar to the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD maps voxelwise approach yields statistically significant prediction scores between mTBI patients with complete and those with incomplete recovery (71.8% specificity, 66.2% F1-score and 0.71 AUC, p < 0.05), which provided a modest increase in the classification score (accuracy: 66.4%) compared with the classification based on age and sex only and ROI-wise approaches (accuracy: 61.4% and 64.7%, respectively). This study showed that ComBat harmonized FA and MD may provide additional information for diagnosis and prognosis of mTBI in a multi-modal machine learning approach. These findings demonstrate that dMRI may assist in the early detection of patients at risk of incomplete recovery from mTBI.

Microbiota from Preterm Infants Who Develop Necrotizing Enterocolitis Drives the Neurodevelopment Impairment in a Humanized Mouse Model.

Necrotizing enterocolitis (NEC) is the leading basis for gastrointestinal morbidity and poses a significant risk for neurodevelopmental impairment (NDI) in preterm infants. Aberrant bacterial colonization preceding NEC contributes to the pathogenesis of NEC, and we have demonstrated that immature microbiota in preterm infants negatively impacts neurodevelopment and neurological outcomes. In this study, we tested the hypothesis that microbial communities before the onset of NEC drive NDI. Using our humanized gnotobiotic model in which human infant microbial samples were gavaged to pregnant germ-free C57BL/6J dams, we compared the effects of the microbiota from preterm infants who went on to develop NEC (MNEC) to the microbiota from healthy term infants (MTERM) on brain development and neurological outcomes in offspring mice. Immunohistochemical studies demonstrated that MNEC mice had significantly decreased occludin and ZO-1 expression compared to MTERM mice and increased ileal inflammation marked by the increased nuclear phospho-p65 of NFκB expression, revealing that microbial communities from patients who developed NEC had a negative effect on ileal barrier development and homeostasis. In open field and elevated plus maze tests, MNEC mice had worse mobility and were more anxious than MTERM mice. In cued fear conditioning tests, MNEC mice had worse contextual memory than MTERM mice. MRI revealed that MNEC mice had decreased myelination in major white and grey matter structures and lower fractional anisotropy values in white matter areas, demonstrating delayed brain maturation and organization. MNEC also altered the metabolic profiles, especially carnitine, phosphocholine, and bile acid analogs in the brain. Our data demonstrated numerous significant differences in gut maturity, brain metabolic profiles, brain maturation and organization, and behaviors between MTERM and MNEC mice. Our study suggests that the microbiome before the onset of NEC has negative impacts on brain development and neurological outcomes and can be a prospective target to improve long-term developmental outcomes.

Association of cognitive-linguistic deficits to diffusion tensor imaging parameters in moderate to severe traumatic diffuse axonal injury

Cognitive-linguistic functions are an essential part of adequate communication competence. Cognitive-linguistic deficits are common after traumatic diffuse axonal injury (DAI). We aimed to examine the integrity of perisylvian white matter tracts known to be associated with linguistic functions in individuals with DAI and their eventual association with poor cognitive-linguistic outcomes. Diffusion tensor imaging (DTI) results of 44 adults with moderate-to-severe DAI were compared with those of 67 controls. Fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF), arcuate fasciculus (AF), SLF with frontal connections to the lower parietal cortex, and AF with temporal connections to the lower parietal cortex were measured using tractography. The associations between white matter integrity FA values and cognitive-linguistic deficits were studied in the DAI group. Cognitive-linguistic deficits were determined based on our earlier study using the novel KAT test. No previous studies have examined the associations between white matter integrity and cognitive-linguistic deficits determined using the KAT test. Patients with DAI showed lower FA values in all left-side tracts than the controls. Unexpectedly, the poor cognitive-linguistic outcome in the language comprehension and production domains was associated with high FA values of several tracts. After excluding five cases with the poorest cognitive-linguistic performance, but with the highest values in the DTI variables, no significant associations with DTI metrics were found. The association between white matter integrity and cognitive-linguistic functioning is complex in patients with DAI of traumatic origin, probably reflecting the heterogeneity of TBI.

More extensive white matter disruptions present in untreated obstructive sleep apnea than we thought: A large sample diffusion imaging study.

Obstructive sleep apnea (OSA) may lead to white mater (WM) disruptions and cognitive deficits. However, no studies have investigated the full extent of the brain WM, and its associations with cognitive deficits in OSA remain unclear. We thus applied diffusion tensor imaging (DTI) tractography with multi-fiber models and used atlas-based bundle-specific approach to investigate the WM abnormalities for various tracts of the cerebral cortex, thalamus, brainstem, and cerebellum in patients with untreated OSA. We enrolled 100 OSA patients and 63 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values mapped on 33 regions of interest including WM tracts of cortex, thalamus, brainstem, and cerebellum were obtained from tractography-based reconstructions. We compared FA/MD values between groups and correlated FA/MD with clinical data in the OSA group after controlling for age and body mass index. OSA patients showed significantly lower FA values in multiple WM fibers including corpus callosum, inferior fronto-occipital fasciculus, middle/superior longitudinal fasciculi, thalamic radiations, and uncinate (FDR <0.05). Higher FA values were found in medial lemniscus of patients compared to controls (FDR <0.05). Lower FA values of rostrum of corpus callosum correlated with lower visual memory performance in OSA group (p < .005). Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism.

Structural and microstructural neuroimaging signature of C9orf72-associated ALS: A multiparametric MRI study

BackgroundALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker. ObjectiveThe objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations. MethodsAtlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients‘ data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed. ResultsThe whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter. ConclusionsThis study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.

Applicability of automated tractography during acute care stroke rehabilitation.

[Purpose] To assess the clinical applicability of a novel automated tractography tool named XTRACT during acute stroke rehabilitation. [Participants and Methods] Three patients with left hemisphere stroke were sampled. Diffusion tensor images were acquired on the second week, and automated tractography was then applied. Tractography images and fractional anisotropy (FA) values in the corticospinal tract (CST) and arcuate fasciculus (AF) were assessed in relation to hemiparesis and aphasia. [Results] Patient 1 was nearly asymptomatic; FA in the left CST was 0.610 and that in the AF was 0.509. Patient 2 had severe hemiparesis and mild motor aphasia. Tractography images of the CST and AF were blurred; FA in the left CST was 0.295 and that in the AF was 0.304. Patient 3 showed no hemiparesis or aphasia at initial assessment. Tractography image of the CST was intact but that of the AF was less clear; FA in the left CST was 0.586 and that in the AF was 0.338. Considering the less clear images of the AF and lower FA value in Patients 2 and 3, further examinations for aphasia were performed, which revealed agraphia. [Conclusion] Visualization and quantification of neural fibers using automated tractography promoted planning acute care rehabilitative treatment in patients with stroke.

Diffusion Tensor MRI of Brain in Healthy Adult Population: Normative Fractional Anisotropy Values at 3 Tesla MRI

Introduction: Diffusion Tensor Imaging (DTI) technique and its clinical application are increasing in clinical routine practice, still very less normative data is available. Awareness regarding regional differences in Fractional Anisotropy (FA) measurements is very important when routinely DTI is used in clinical Magnetic Resonance Imaging (MRI). Aim: To determine the normative FA values data at 3 Tesla (3T) MRI and to determine the degradation of FA values in various regions of brain values with age. Materials and Methods: This cross-sectional study involved a total of 52 participants without any abnormal findings ( presence of tumour, stroke, infarct, degeneration, etc) and whose brain scanning was performed at 3T MRI, in the Department of Radiodiagnosis, Shree Krishna Hospital, and Pramukhswami Medical College, Karamsad, Anand, Gujarat, India. A DTI protocol was set for the healthy patient’s brain scanning. The colour-coded DTI brain images were postprocessed carefully to draw a circular Region of Interest (ROI) in the required areas of white matter and FA values were noted. Descriptive statistics were used to find out the normative data in 11 regions of the brain on right and left side. Pearson correlation was used to check the correlation of FA values with age. Results: There were 52 patients in the present study, with a male to female ratio of 1.7:1 and a mean age of 52 years. The highest FA values were observed in the splenium (0.809), genu (0.767), the body of the corpus callosum (0.627), and the posterior limb of the internal capsule (0.721), rest areas showed moderate to low FA values. Pearson correlation was used to find the variation in the FA values with age in three age groups 18-40, 41-60 and &gt;60 years, where moderate changes in FA values with age were seen in a few regions of the brain such as genu (right side) with p-value=0.003 and foramen magnum at CVJ level (right side) with a p-value of 0.001. Conclusion: Generally, FA values intend to change with the presence of multiple tract areas, field strength, coil sensitivity, and partial volume averaging. FA values were also found to be affected with respect to increasing age.