Fiber-bundle Cross-section Research Articles

Fixel-Based Analysis of White Matter Alterations in Facial Palsy.

Predicting individual prognosis is difficult despite various risk factor studies, due to the complex recovery involving peripheral nerve restoration and cerebral plasticity. This study uses fixel-based analysis (FBA) to better understand neural pathway alterations, hypothesizing that FBA can effectively link functional outcomes with diffusion metrics in the process of rehabilitation. The authors recruited 50 participants including 30 patients and 20 healthy controls into the study. All of them underwent assessment 3 months and 6 months after injury. Both whole-brain fixel-based analysis and tract of interest analysis were performed. The authors observed multiple regions including the superior corona radiata, posterior limb of the internal capsule, and cerebral peduncle displaying significant changes of FD (fiber density), FC (fiber-bundle cross-section), and FDC (fiber density and cross-section). Patients with unfavorable outcomes showed increased FD in the ipsilesional side and decreased FD in the contralesional side compared with patients with favorable outcomes. In addition, FD values of the contralesional side exhibited positive correlations with differences in FGS at 3 months and 6 months. Conversely, FD values in the ipsilesional side showed a negative correlation. Our findings suggest that FD metrics within the corticobulbar tract could serve as predictive biomarkers for symmetry outcomes. Thus, FBA holds promise for early estimation of behavioral outcomes in facial palsy, guiding more targeted interventions.

Music reward sensitivity is associated with greater information transfer capacity within dorsal and motor white matter networks in musicians.

There are pronounced differences in the degree to which individuals experience music-induced pleasure which are linked to variations in structural connectivity between auditory and reward areas. However, previous studies exploring the link between white matter structure and music reward sensitivity (MRS) have relied on standard diffusion tensor imaging methods, which present challenges in terms of anatomical accuracy and interpretability. Further, the link between MRS and connectivity in regions outside of auditory-reward networks, as well as the role of musical training, have yet to be investigated. Therefore, we investigated the relation between MRS and structural connectivity in a large number of directly segmented and anatomically verified white matter tracts in musicians (n = 24) and non-musicians (n = 23) using state-of-the-art tract reconstruction and fixel-based analysis. Using a manual tract-of-interest approach, we additionally tested MRS-white matter associations in auditory-reward networks seen in previous studies. Within the musician group, there was a significant positive relation between MRS and fiber density and cross section in the right middle longitudinal fascicle connecting auditory and inferior parietal cortices. There were also positive relations between MRS and fiber-bundle cross-section in tracts connecting the left thalamus to the ventral precentral gyrus and connecting the right thalamus to the right supplementary motor area, however, these did not survive FDR correction. These results suggest that, within musicians, dorsal auditory and motor networks are crucial to MRS, possibly via their roles in top-down predictive processing and auditory-motor transformations.

White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric concussion: a fixel-based analysis.

Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion. This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts. Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3). Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis.

Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states,physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured usingan immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aβ42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aβ42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.

White Matter Alterations of Visual Pathway in Thyroid Eye Disease: A Fixel-Based Analysis.

Thyroid eye disease (TED), particularly its sight-threatening complication, dysthyroid optic neuropathy (DON), profoundly impacts patients' visual health. The pathological changes in the white matter (WM) fibers within the intracranial visual pathway in TED have been infrequently studied. Understanding these changes holds crucial importance for exploring the pathogenesis and prognosis of TED. To utilize fixel-based analysis (FBA) to clarify the type of microstructural damage occurring in the visual pathway in TED. Prospective. 28 TED with DON patients (11 males and 17 females), 28 TED without DON (non-DON) patients (12 males and 16 females), and 28 healthy controls (HCs) (12 males and 16 females). 3 T; multishell diffusion MRI using echo planar imaging. Fiber density (FD) and fiber-bundle cross-section (FC) were calculated to characterize WM microstructural alteration in TED visual pathway. The correlations between FBA metrics and visual field index and mean deviation were examined. One-way analysis of variance, Kruskal-Wallis, t-tests, Mann-Whitney U, Chi-square, and Pearson correlation, were conducted with false discovery rate and family wise error corrections. Significance was set at P < 0.05. Both DON and non-DON groups showed significant FD loss in the right optic tract compared with HCs, with DON patients experiencing more severe FD loss. Only DON patients had FD loss in the right optic radiation (OR) compared with the non-DON patients and HCs, with no FC difference across groups. FD in DON patients' ORs significantly correlated with visual field index (r = 0.857) and mean deviation (r = 0.751). Both DON and non-DON affect the WM microstructure of the visual pathway to varying extents. Visual field metrics can reflect the severity of FD damage to the OR in the visual pathway of DON patients. 2. Stage 3.

Pretreatment Brain White Matter Integrity Associated With Neuropathic Pain Relief and Changes in Temporal Summation of Pain Following Ketamine

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis of diffusion-weighted imaging data to evaluate WM microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent magnetic resonance imaging and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1 month after treatment; those with ≥30% pain relief were considered responders (n = 18), or otherwise as nonresponders (n = 17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from nonresponders. However, pretreatment FD in the anterior limb of the internal capsule correlated with pain relief (r=.48). Moreover, pretreatment FD in the DMN (left mPFC-precuneus/posterior cingulate cortex; r=.52) and mPFC-PAG (r=.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PerspectiveWe used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pretreatment WM microstructure associated with ketamine outcomes, including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with NP.

Differential influences of rest tremor on brain fiber architecture in essential tremor and Parkinson's disease

BackgroundRest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear. MethodsThis study included 57 ET patients (40 without rest tremor (ETWR), 17 with rest tremor (ETRT)), 68 PD patients (34 without rest tremor (PDWR), 34 with rest tremor (PDRT)), and 62 normal controls (NC). Fixel-based analysis was used to evaluate the structural changes of white matter in rest tremor in these different diseases. ResultsThe fiber-bundle cross-section (FC) of the right non-decussating dentato-rubro-thalamic tract and several fibers outside the dentato-rubro-thalamic pathway in ETWR were significantly higher than that in NC. The fiber density and cross-section of the left nigro-pallidal in PDWR is significantly lower than that in NC, while the FC of bilateral nigro-pallidal in PDRT is significantly lower than that in NC. ConclusionET patients with pure action tremor showed over-activation of fiber tracts. However, when superimposed with rest tremor, ET patients no longer exhibited over-activation of fiber tracts, but rather showed a trend of fiber tract damage. Except for the nigro-pallidal degeneration in all PD, PDRT will not experience further deterioration in fiber organization. These results provide important insights into the unique effects of rest tremor on brain fiber architecture in ET and PD.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. Prospective. Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2). Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

Progressive white matter degeneration in patients with spinocerebellar ataxia type 2.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder characterized by cerebellar atrophy. However, studies to elucidate the longitudinal progression of the neuropathology are limited. We sought to identify brain macrostructural and microstructural alterations in patients with SCA2 using fixel-based analysis (FBA) to better understand its distribution patterns and progression. We enrolled 9 patients with SCA2 and 16 age- and gender-matched controls. Longitudinal clinical and imaging data were collected at baseline, and 3.5 years later. Fiber density (FD), fiber-bundle cross-section (FC), and a combination of FD and FC (FDC) were calculated. The paired t-test was used to examine longitudinal differences. The associations between fixel-based metrics and clinical variables were explored in SCA2 patients. At baseline, patients with SCA2 displayed multiple white matter tracts with significantly decreased FD, FC, and FDC in the corticospinal tract, cerebellar peduncles, brainstem, corpus callosum, thalamus, striatum, and prefrontal cortex, compared to controls. Over time, many of these macrostructural and microstructural alterations progressed, manifesting lower FD, FC, and FDC in corticospinal tract, middle cerebellar peduncle, brainstem, striatum, fornix, and cingulum. No significant brain white matter alterations were found in the healthy controls over time. There was no association between the FBA-derived metrics and clinical variables in SCA2. This study provides evidence of brain macrostructural and microstructural alterations and of progression over time in SCA2. The FBA-derived metrics may serve as potential biomarkers of SCA2 progression.

A fixel-based analysis of white matter reductions early detects Parkinson disease with mild cognitive impairment

BackgroundWhite matter (WM) tract alterations are early signs of cognitive impairment in Parkinson disease (PD) patients. Fixel-based analysis (FBA) has advantages over traditional diffusion tensor imaging in managing complex and crossing fibers. We used FBA to measure fiber-specific changes in patients with PD mild cognitive impairment (PD-MCI) and PD normal cognition (PD-NC). MethodsSeventy-one patients with PD without dementia were included: 39 PD-MCI and 32 PD-NC. All underwent diffusion-weighted imaging, clinical examinations, and tests to evaluate their cognitive function globally and in five cognitive domains. FBA was used to investigate fiber-tract alterations and compare PD-MCI with PD-NC subjects. Correlations with each cognitive test were analyzed. ResultsPatients with PD-MCI were significantly older (p = 0.044), had a higher male-to-female ratio (P = 0.006) and total Unified Parkinson's Disease Rating Scale score (P = 0.001). All fixel-based metrics were significantly reduced within the body of the corpus callosum and superior corona radiata in PD-MCI patients (family-wise error-corrected P value < 0.05) compared with PD-NC patients. The cingulum, superior longitudinal fasciculi, and thalamocortical circuit exhibited predominantly fiber-bundle cross-section (FC) changes. In regression analysis, reduced FC values in cerebellar circuits were associated with poor motor function in PD-MCI patients and poor picture-naming ability in PD-NC patients. ConclusionsPD-MCI patients have significant WM alterations compared with PD-NC patients. FBA revealed these changes in various bundle tracts, helping us to better understand specific WM changes that are functionally implicated in PD cognitive decline. FBA is potentially useful in detecting early cognitive decline in PD.

Fiber-Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations.

Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD). The objective of this study was to investigate fiber-specific white matter (WM) differences in nonmedicated patients with early-stage GBA-PD and iPD using fixel-based analysis, a novel technique to assess tract-specific WM microstructural and macrostructural features comprehensively. Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA-PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses. Patients with GBA-PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal-thalamo-cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal-thalamo-cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA-PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α-synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores. We report reduced fiber-specific WM density and bundle cross-sectional size in patients with GBA-PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α-synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Fiber-specific white matter alterations in Parkinson’s disease patients with freezing of gait

Freezing of gait (FOG) is a gait disorder that usually occurs in advanced stages of Parkinson's disease (PD). Understanding the underlying mechanism of FOG is important for treatment and prevention. Previous studies have investigated white matter (WM) structure to explore the pathology of FOG. However, the pathology is still unclear, possibly due to the methodological limitation in identifying specific fiber tracts. This study aimed to investigate tract-specific WM structural changes in FOG patients and their relationships with clinical characteristics. We enrolled 19 PD patients with FOG (PD-FOG), 19 without FOG (PD-woFOG) and 21 controls. Fixel-based analysis is a novel framework to avoid the effect of crossing fibers, which provides the metrics to assess WM morphology. By combining a method for segmenting fibers, we identified abnormalities in the specific fiber tracts. Compared to PD-woFOG, PD-FOG showed significant increased fiber-bundle cross-section (FC) in the corpus callosum (CC), fornix (FX), inferior longitudinal fasciculus (ILF), striato-premotor (ST_PREM), superior thalamic radiation (STR), thalamo-premotor (T_PREM), increased fiber density and cross-section (FDC) in the STR, and decreased fiber density (FD) in the CC and ILF. Additionally, the ILF was correlated with motor, cognition and memory, the CC was correlated with anxiety, and the T_PREM was also correlated with cognition. In conclusion, in addition to impairments of WM found in PD-FOG, we found enhancements in WM, which may imply compensatory mechanisms. Furthermore, multiple fiber tracts were correlated with clinical characteristics, especially the ILF, validating the involvement of transmission circuits of multiple distinct information in mechanisms of FOG.

Research and modelling of fiber deformation mechanism of 3D four-direction preform under compression loading

In order to investigate further the compaction characteristics of the three-dimensional four-direction preform of carbon/carbon composite, a model of three-dimensional four-direction numerical preform at the micro-scale was established using the programming language in Python based on the ABAQUS simulation platform more realistically to reflect the micro-structure of the preform. A model of three-dimensional fiber numerical growth was built to describe the changes of fiber bundle cross-section under compressive load considering the random distribution, deflection, bending and the physical characteristics of fibers not penetrating each other in three-dimensional space. In addition to exploring the characteristics of the fiber bundle compaction process in the inter-laminar dimension, the interaction between laminated fibers of the preform was analyzed; the method of finite element was employed to construct a compaction model of the three-dimensional four-direction preform; the deformation of inter-laminar fibers under compressive load was studied by the numerical simulation method; the nonlinear mapping relationship between compressive load and compaction height consistent with the preform compaction experiment was obtained. The results demonstrated that the deflection coefficient of the numerical model was 0.32, which was most consistent with the actual result.

Longitudinal Trajectories of White Matter Development in Attention-Deficit/Hyperactivity Disorder

BackgroundFew longitudinal studies have investigated whether white matter development reflects differential outcomes for children with and without attention-deficit/hyperactivity disorder (ADHD). To examine whether deviations from typical trajectories of white matter development were associated with the persistence or remission of ADHD symptoms, this study examined microstructural and morphological properties of 71 white matter tracts from 390 high angular diffusion scans acquired prospectively for 62 children with persistent ADHD, 37 children remitted from ADHD, and 85 children without ADHD. MethodsParticipants (mean age at wave 1 = 10.39 years, scan interval = 18 months) underwent up to 3 magnetic resonance imaging assessments. White matter tracts were reconstructed using TractSeg, a semiautomated method. For each tract, we derived measures of fiber density (microstructure) and fiber bundle cross-section (morphology) using fixel-based analysis. Linear mixed models were used to compare trajectories of fiber development between the persistent ADHD, remitted ADHD, and non-ADHD groups. ResultsCompared with the non-ADHD group, the remitted and persistent ADHD groups showed accelerated fiber development in thalamic pathways, striatal pathways, and the superior longitudinal fasciculus. In the remitted ADHD group, accelerated fiber development in corticospinal, frontopontine, striatal-premotor, and thalamo-premotor pathways was associated with greater reductions in ADHD symptom severity. The persistent ADHD group showed ongoing white matter alterations along sensorimotor pathways. ConclusionsThese results suggest that variations in white matter development are associated with different clinical trajectories in ADHD. The findings advance our understanding of the neurobiological mechanisms underpinning ADHD symptom progression and provide novel evidence in support of developmental models of ADHD.

Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke.

Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions. Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract-specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error-corrected p < 0.05, nonparametric testing over 5,000 permutations). We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory. We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment. ClinicalTrails.gov NCT02205424.

Fatigue life prediction of 3D braided carbon/carbon composites with braided angle variation at elevated temperature

The braiding angle of 3D braided carbon/carbon composites (C/CCs) will change during high temperature fatigue loading, which will affect the fatigue properties of 3D braided C/CCs. In order to realize this dynamic simulation in the high temperature fatigue life prediction of 3D braided C/CCs and further improve the prediction accuracy of high temperature fatigue life of 3D braided C/CCs, a high temperature fatigue life prediction model of 3D braided C/CCs considering the change of braiding angle with fatigue cycle number was established. The establishment of the prediction model mainly includes: a meso-scale representative volume elements (RVEs) of 3D braided C/CCs considering yarn direction and fiber bundle cross-section shape is established at the meso-scale; the high temperature residual stiffness and residual strength models of fiber bundles considering high temperature and stress level are established. Based on the experimental data characteristics of high temperature fatigue residual stiffness of 3D braided C/CCs, a mathematical model of cycle number/braided angles (CN/BAs) is established. The fatigue life prediction model was used to predict the 3D braided C/CCs at 700°C and stress levels of 87% and 85%. The results showed that the prediction error of single flower node was less than 5%. The fatigue life prediction error is less than two times the tolerance.

White matter and sustained attention in children with attention/deficit-hyperactivity disorder: A longitudinal fixel-based analysis.

Sustained attention is a cognitive function with known links to academic success and mental health disorders such as attention/deficit-hyperactivity disorder (ADHD). Several functional networks are critical to sustained attention, however the association between white matter maturation in tracts linking functional nodes and sustained attention in typical and atypical development is unknown. 309 diffusion-weighted imaging scans were acquired from 161 children and adolescents (80 ADHD, 81 control) at up to three timepoints over ages 9-14. A fixel-based analysis approach was used to calculate mean fiber density and fiber-bundle cross section in tracts of interest. Sustained attention was measured using omission errors and response time variability on the out-of-scanner sustained attention to response task. Linear mixed effects models examined associations of age, group and white matter metrics with sustained attention. Greater fiber density in the bilateral superior longitudinal fasciculus (SLF) I and right SLF II was associated with fewer attention errors in the control group only. In ADHD and control groups, greater fiber density in the left ILF and right thalamo-premotor pathway, as well as greater fiber cross-section in the left SLF I and II and right SLF III, was associated with better sustained attention. Relationships were consistent across the age span. Results suggest that greater axon diameter or number in the dorsal and middle SLF may facilitate sustained attention in neurotypical children but does not assist those with ADHD potentially due to disorder-related alterations in this region. Greater capacity for information transfer across the SLF was associated with attention maintenance in 9-14-year-olds regardless of diagnostic status, suggesting white matter macrostructure may also be important for attention maintenance. White matter and sustained attention associations were consistent across the longitudinal study, according with the stability of structural organization over this time. Future studies can investigate modifiability of white matter properties through ADHD medications.

Fiber-Specific Measures of White Matter Microstructure and Macrostructure Are Associated With Internalizing and Externalizing Symptoms in Children Born Very Preterm and Full-term

BackgroundTensor-based investigations suggest that delayed or disrupted white matter development may relate to adverse behavioral outcomes in individuals born very preterm (VP); however, metrics derived from such models lack specificity. Here, we applied a fixel-based analysis framework to examine white matter microstructural and macrostructural correlates of concurrent internalizing and externalizing problems in VP and full-term (FT) children at 7 and 13 years. MethodsDiffusion imaging data were collected in a longitudinal cohort of VP and FT individuals (130 VP and 29 FT at 7 years, 125 VP and 44 FT at 13 years). Fixel-based measures of fiber density, fiber-bundle cross-section, and fiber density and cross-section were extracted from 21 white matter tracts previously implicated in psychopathology. Internalizing and externalizing symptoms were assessed using the Strengths and Difficulties Questionnaire parent report at 7 and 13 years. ResultsAt age 7 years, widespread reductions in fiber-bundle cross-section and fiber density and cross-section and tract-specific reductions in fiber density were related to more internalizing and externalizing symptoms irrespective of birth group. At age 13 years, fixel-based measures were not related to internalizing symptoms, while tract-specific reductions in fiber density, fiber-bundle cross-section, and fiber density and cross-section measures were related to more externalizing symptoms in the FT group only. ConclusionsAge-specific neurobiological markers of internalizing and externalizing problems identified in this study extend previous tensor-based findings to inform pathophysiological models of behavior problems and provide the foundation for investigations into novel preventative and therapeutic interventions to mitigate risk in VP and other high-risk infant populations.

White matter fiber-specific degeneration in older adults with metabolic syndrome

ObjectiveMetabolic syndrome (MetS) is defined as a complex of interrelated risk factors for type 2 diabetes and cardiovascular disease, including glucose intolerance, abdominal obesity, hypertension, and dyslipidemia. Studies using diffusion tensor imaging (DTI) have reported white matter (WM) microstructural abnormalities in MetS. However, interpretation of DTI metrics is limited primarily due to the challenges of modeling complex WM structures. The present study used fixel-based analysis (FBA) to assess the effect of MetS on the fiber tract-specific WM microstructure in older adults and its relationship with MetS-related measurements and cognitive and locomotor functions to better understand the pathophysiology of MetS. MethodsFixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross-section (FC), and a combination of FD and FC (FDC), were evaluated in 16 healthy controls (no components of MetS; four men; mean age, 71.31 ± 5.06 years), 57 individuals with premetabolic syndrome (preMetS; one or two components of MetS; 29 men; mean age, 72.44 ± 5.82 years), and 46 individuals with MetS (three to five components of MetS; 27 men; mean age, 72.15 ± 4.97 years) using whole-brain exploratory FBA. Tract of interest (TOI) analysis was then performed using TractSeg across 14 selected WM tracts previously associated with MetS. The associations between fixel-based metrics and MetS-related measurements, neuropsychological, and locomotor function tests were also analyzed in individuals with preMetS and MetS combined. In addition, tensor-based metrics (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) were compared among the groups using tract-based spatial statistics (TBSS) analysis. ResultsIn whole-brain FBA, individuals with MetS showed significantly lower FD, FC, and FDC compared with healthy controls in WM areas, such as the splenium of the corpus callosum (CC), corticospinal tract (CST), middle cerebellar peduncle (MCP), and superior cerebellar peduncle (SCP). Meanwhile, in fixel-based TOI, significantly reduced FD was observed in individuals with preMetS and MetS in the anterior thalamic radiation, CST, SCP, and splenium of the CC compared with healthy controls, with relatively greater effect sizes observed in individuals with MetS. Compared with healthy controls, significantly reduced FC and FDC were only demonstrated in individuals with MetS, including regions with loss of FD, inferior cerebellar peduncle, inferior fronto-occipital fasciculus, MCP, and superior longitudinal fasciculus part I. Furthermore, negative correlations were observed between FD and Brinkman index of cigarette consumption cumulative amount and between FC or FDC and the Trail Making Test (parts B–A), which is a measure of executive function, waist circumference, or low-density lipoprotein cholesterol. Finally, TBSS analysis revealed that FA and MD were not significantly different among all groups. ConclusionsThe FBA results demonstrate that substantial axonal loss and atrophy in individuals with MetS and early axonal loss without fiber-bundle morphological changes in those with preMetS within the WM tracts are crucial to cognitive and motor function. FBA also clarified the association between executive dysfunction, abdominal obesity, hyper-low-density lipoprotein cholesterolemia, smoking habit, and compromised WM neural tissue microstructure in MetS.

Advanced diffusion-weighted imaging models better characterize white matter neurodegeneration and clinical outcomes in multiple sclerosis.

White matter (WM) atrophy is relevant in multiple sclerosis (MS), but the methods of analysis currently used are not specific for microstructural changes. The aims of this study were to assess the use of advanced diffusion-weighted imaging (DWI) techniques proposed as measures of baseline and longitudinal WM atrophy in MS and to analyze whether these measures helped explain MS clinical disability (including cognitive impairment) better than volumetric and diffusion tensor (DT)-derived measures. 3DT1-weighted and DWI sequences were applied to 86 MS and 55 healthy controls (HC) at baseline and after one-year. Intra-cellular volume (vic) maps were computed from neurite orientation dispersion and density imaging model. Voxel-wise fiber-bundle cross-section (FCS) atrophy in MS compared to HC was estimated. Maps of fractional anisotropy and mean diffusivity were also obtained from DWI for a comparison with the proposed advanced DW-derived measures (vic and FCS). Both at baseline and after 1-year, only FCS measure showed a significant atrophy in relapsing-remitting (RR) MS compared to HC and in progressive MS compared to RRMS, mainly located in specific WM tracts (corticospinal tract, splenium of the corpus callosum, left optic radiation, bilateral cingulum, middle cerebellar peduncle and anterior commissure, p value < 0.05). Global baseline FCS and vic were the selected predictors of clinical (R-sq = 0.33, p = 0.007) and cognitive scores (R-sq = 0.29, p = 0.0014) in a linear regression model. Voxel-based FCS was able to detect WM tracts atrophy in MS clinical phenotypes with greater anatomical specificity compared to other measures (volumetric and DT-derived measures of WM damage). FCS and vic measured at baseline in the WM were the best predictors of clinical disability and cognitive impairment.