Fractional Anisotropy Changes Research Articles

White Matter Microstructure Organization Across the Transition to Fatherhood

The transition to parenthood remains an understudied window of potential neuroplasticity in the adult brain. White matter microstructural (WMM) organization, which reflects structural connectivity in the brain, has shown plasticity across the lifespan. No studies have examined how WMM organization changes from the prenatal to postpartum period in men becoming fathers. This study investigates WMM organization in men transitioning to first-time fatherhood. We performed diffusion-weighted imaging to identify differences in WMM organization, as indexed by fractional anisotropy (FA). We also investigated whether FA changes were associated with fathers’ postpartum mental health. Associations between mental health and WMM organization have not been rarely examined in parents, who may be vulnerable to mental health problems. Fathers exhibited reduced FA at the whole-brain level, especially in the cingulum, a tract associated with emotional regulation. Fathers also displayed reduced FA in the corpus callosum, especially in the forceps minor, which is implicated in cognitive functioning. Postpartum depressive symptoms were linked with increases and decreases in FA, but FA was not correlated with perceived or parenting stress. Findings provide novel insight into fathers’ WMM organization during the transition to parenthood and suggest postpartum depression may be linked with fathers’ neuroplasticity during the transition to parenthood.

Heading during the season and its potential impact on brain structure and neurocognitive performance in high-level male football players: an observational study

ObjectiveTo investigate potential effects of heading on the neurocognitive performance and the white matter (WM) of the brain in high-level adult male football players. DesignProspective longitudinal. MethodFootball players engaging in the highest football leagues in Germany were included. Neurocognitive performance tests and diffusion tensor imaging (DTI) were executed before and after the observation period. Video recordings of each training session and each match play during the observation period were analyzed regarding heading exposure and characteristics. Four DTI measures from tract-based spatial statistics (fractional anisotropy, mean, axial, and radial diffusivity) were investigated. Associations between heading variables and DTI and neurocognitive parameters were tested subsequently. Results8052 headers of 22 players (19.9 ± 2.7 years) were documented in a median of 16.9 months. The individual total heading number ranged from 57 to 943 (median: 320.5). Header characteristics differed between training sessions and matches. Neurocognitive performance (n = 22) and DTI measures (n = 14) showed no significant differences from pre- to post-test. After correction for multiple comparisons, no significant correlations with the total heading number were found. However, the change in fractional anisotropy in the splenium of the corpus callosum correlated significantly with the total amount of long-distance headers (Pearson's r = −0.884; p < 0.0001). ConclusionOver the median observation period of 16.9 months, DTI measures and neurocognitive performance remained unchanged. To elucidate the meaning of the association between individual change in fractional anisotropy and long-distance headers further investigations with larger samples, longer observations, and various cohorts regarding age and level of play are required.

190 Do Fractional Anisotropy and Apparent Diffusion Coefficient From Diffusion Tensor Imaging Correlate to Symptoms of Radiculopathy? A Case Series From BACPAC MRI

INTRODUCTION: Quantitative diffusion tensor imaging (DTI) parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are used to detect axonal pathology in nerve injuries. METHODS: Ganglia of the lumbar plexus nerves (L1-5) were input as seeds to track the nerve fibers using Constant Solid Angle reconstruction. Fiber tracts and values of FA and ADC were extracted along the lumbar plexus nerve profiles. Change in pain (VAS) and disability (ODI) after interlaminar epidural steroid injection at site of compression was compared to the changes in FA and ADC values. RESULTS: Five exams from three patients with bilateral L4-5 foraminal narrowing were included in this study. Two patients were imaged at two time points, three months apart. The average age of the cohort was 62.6 ± 5.3 years. Mean FA values were lowest at L3 (left: 0.32 ± 0.08; right: 0.35 ± 0.05) and L4 (left: 0.39 ± 0.06; right: 0.38 ± 0.03). Correspondingly, mean ADC values were highest at L3 (left: 0.0017 ± 0.0002; right: 0.0016 ± 0.0001) and L4 (left: 0.0.0013 ± 0.0001; right: 0.0015 ± 0.0002). For one patient, pain did not change in severity and ODI improved from severe to moderate disability after steroid injection: FA increased with no significant change in ADC. For another patient, pain increased from moderate to severe and ODI stayed the same after injection: FA decreased and ADC did not significantly change. CONCLUSIONS: The tractography generated from the segmentation model demonstrated lowest FA and highest ADC values corresponding to the level of compression. For patient outcomes, the FA values were observed to be more sensitive to changes in pain and disability compared to the ADC values.

Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P < 0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

Correlation between postoperative microstructural changes in cerebral white matter and early postoperative cognitive function in patients undergoing meningioma resection

Objective: To analyze the correlation between microstructure changes in cerebral white matter before and after surgery and early postoperative cognitive function in patients undergoing meningioma resection. Methods: A total of 17 patients who underwent their first meningioma resection at Xuanwu Hospital of Capital Medical University from April 2022 to April 2023 were prospectively included as observation group, with 5 males and 12 females, aged (56.4±7.3) years. Another 15 age- and education-matched patients with cerebral benign tumor were recruited as control group during the same period, with 5 males and 10 females, aged (55.2±8.0) years. Neuropsychological tests (NST), mainly including auditory verbal learning test of Huashan version (AVLT-H), the Montreal cognitive assessment-basic (MoCA-B), clock drawing task-30 (CDT-30), shape trails test-B (STT-B) and animal fluence test (AFT), were conducted at 1 day before surgery, 1 day and within 3-4 days after surgery in the observation group. Simultaneously, magnetic resonance imaging (MRI) scans were performed to collect diffusion tensor imaging (DTI) images at 1 day before surgery and within 3-4 days after surgery. The same NST were conducted at 1 day, 3 days and 6 days after admission in the control group to adjust for learning effects from repeated tests. The microstructure changes of the whole brain white matter were evaluated at the group level by using tract-based spatial statistics (TBSS) technology, including changes of fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD). Then, correlation was performed between DTI indicators with statistically significant and cognitive function. Results: After adjusting for the learning effects, the AVLT-H (R), MoCA-B, and CDT-30 scores decreased, and the evaluation time of STT-B prolonged after surgery in patients with meningioma. And their perioperative decreased values were -0.78 (95%CI:-3.28--0.28) points, -2.22 (95%CI:-4.22--0.72) points, -2.74 (95%CI:-5.29--0.19) points, and 61.49 (95%CI: 5.71-117.27) seconds, respectively, with statistically significant differences (all P<0.05). Group level analysis of TBSS based on DTI images showed decreased FA mainly in the right superior cerebellar peduncle, left posterior limb of internal capsule and genu of corpus callosum, and increased RD mainly in the left anterior corona radiata in patients undergoing meningioma resection, with statistically significant differences (all PFWE<0.05). Linear correlation showed that the perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle were positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects (r=0.72, 0.52, all PFWE<0.05). Conclusions: Patients undergoing meningioma resection are at risk of postoperative cognitive decline. Perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle based on DTI images are positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects.

Subtle microstructural alterations in white matter tracts involved in socio-emotional processing after very preterm birth

Children born very preterm (VPT, < 32 weeks of gestation) have an increased risk of developing socio-emotional difficulties. Possible neural substrates for these socio-emotional difficulties are alterations in the structural connectivity of the social brain due to premature birth. The objective of the current study was to study microstructural white matter integrity in VPT versus full-term (FT) born school-aged children along twelve white matter tracts involved in socio-emotional processing. Diffusion MRI scans were obtained from a sample of 35 VPT and 38 FT 8-to-12-year-old children. Tractography was performed using TractSeg, a state-of-the-art neural network-based approach, which offers investigation of detailed tract profiles of fractional anisotropy (FA). Group differences in FA along the tracts were investigated using both a traditional and complementary functional data analysis approach. Exploratory correlations were performed between the Social Responsiveness Scale (SRS-2), a parent-report questionnaire assessing difficulties in social functioning, and FA along the tract. Both analyses showed significant reductions in FA for the VPT group along the middle portion of the right SLF I and an anterior portion of the left SLF II. These group differences possibly indicate altered white matter maturation due to premature birth and may contribute to altered functional connectivity in the Theory of Mind network which has been documented in earlier work with VPT samples. Apart from reduced social motivation in the VPT group, there were no significant group differences in reported social functioning, as assessed by SRS-2. We found that in the VPT group higher FA values in segments of the left SLF I and right SLF II were associated with better social functioning. Surprisingly, the opposite was found for segments in the right IFO, where higher FA values were associated with worse reported social functioning. Since no significant correlations were found for the FT group, this relationship may be specific for VPT children. The current study overcomes methodological limitations of previous studies by more accurately segmenting white matter tracts using constrained spherical deconvolution based tractography, by applying complementary tractometry analysis approaches to estimate changes in FA more accurately, and by investigating the FA profile along the three components of the SLF.

ANISOTROPIA FRACIONADA NO PROGNÓSTICO DE CIRURGIA DE ESTENOSE CERVICAL DEGENERATIVA: REVISÃO SISTEMÁTICA

ABSTRACT Cervical spondylotic myelopathy (CSM) is a common disease with an increased anticipated burden to health systems worldwide. Methods to predict outcomes in these patients are needed so physicians can provide more effective care. Fractional anisotropy (FA) analysis is a promising technique used to quantify how preserved the diffusion is in neural pathways. A systematic review and meta-analysis were performed using the PRISMA guidelines. Full articles available online were searched for correlation coefficients between FA values and mJOA scores. Average FA values, preoperative mJOA, and postoperative mJOA scores were gathered to perform a correlation analysis. A total of 5 articles presented correlations between FA and mJOA change and were included in the correlation meta-analysis. Correlation coefficients varied from -0.42 and 0.55. The number of patients in each study varied from 15 to 95. The Random effects model resulted in a non-significant correlation coefficient of 0.1315 (95% CI: -0.2575 to 0.4839; p= 0.5124). Spearman's correlation analysis was significant for preoperative vs postoperative mJOA (r = 0.79, p = 0.02), while preoperative FA did not correlate significantly with preoperative or postoperative mJOA. At this point, the data available in the literature is insufficient to determine a real correlation between FA and mJOA scores. More studies are necessary for a better understanding of this matter. Level of Evidence III; Study Review.

Quantitative magnetic resonance neurography in chronic inflammatory demyelinating polyradiculoneuropathy: A longitudinal study over 6 years.

To evaluate magnetic resonance neurography (MRN) for the longitudinal assessment of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Prospective examination of twelve CIDP patients by neurological assessment, MRN, and nerve conduction studies in 2016 and 6 years later in 2022. Imaging parameters were compared with matched healthy controls and correlated with clinical and electrophysiological markers. The MRN protocol included T2-weighted imaging, diffusion tensor imaging (DTI), T2 relaxometry, and magnetization transfer imaging (MTI). Nerve cross-sectional area (CSA) was increased in CIDP patients compared to controls (plexus: p = 0.003; sciatic nerve: p < 0.001). Over 6 years, nerve CSA decreased in CIDP patients, most pronounced at the lumbosacral plexus (p = 0.015). Longitudinally, changes in CSA correlated with changes in the inflammatory neuropathy cause and treatment validated overall disability sum score (INCAT/ODSS) (p = 0.006). High initial nerve CSA was inversely correlated with changes in the INCAT/ODSS over 6 years (p < 0.05). The DTI parameter fractional anisotropy (FA) showed robust correlations with electrodiagnostic testing both cross-sectionally and longitudinally (p < 0.05). MTI as a newly added imaging technique revealed a significantly reduced magnetization transfer ratio (MTR) in CIDP patients (p < 0.01), suggesting underlying changes in macromolecular tissue composition, and correlated significantly with electrophysiological parameters of demyelination (p < 0.05). This study provides evidence that changes in nerve CSA and FA reflect the clinical and electrophysiological course of CIDP patients. Initial nerve hypertrophy might predict a rather benign course or better therapy response.

Diffusion tensor-based analysis of white matter in dogs with idiopathic epilepsy.

The understanding of epileptic seizure pathogenesis has evolved over time, and it is now generally accepted that not only are cortical and subcortical areas involved but also the connection of these regions in the white matter (WM). Recent human neuroimaging studies confirmed the involvement of the WM in several epilepsy syndromes. Neuroimaging studies investigating WM integrity with diffusion tensor imaging (DTI) in canine idiopathic epilepsy are lacking. This study aimed to test the hypothesis that WM diffusion changes can be found in dogs affected by idiopathic epilepsy. Twenty-six dogs with idiopathic epilepsy (15 Border Collies and 11 Greater Swiss Mountain dogs) and 24 healthy controls (11 Beagle dogs, 5 Border Collies, and 8 Greater Swiss Mountain dogs) were prospectively enrolled. Most dogs with idiopathic epilepsy (17/26) were enrolled within 3 months after seizure onset. Diffusion tensor imaging of the brain with 32 diffusion directions (low b value = 0 s/mm2; maximal b value = 800 s/mm2) was performed in a 3 Tesla scanner. Tract-based spatial statistics (TBSS), a voxel-based approach, was used to investigate changes in fractional anisotropy (FA) and mean diffusivity (MD) in the idiopathic epilepsy group compared to the healthy control group. Additionally, FA and MD were investigated in the region of corpus callosum and cingulate white matter in both groups. We observed subtle changes in WM DTI between the idiopathic epilepsy group and the healthy control group limited to cingulate WM, with a significantly lower FA in the idiopathic epilepsy group compared to the healthy control group in the region of interest (ROI) approach (p = 0.027). No significant changes were found between the idiopathic epilepsy group and the healthy control group in the TBSS analysis and in the corpus callosum in the ROI approach. This study supports the cingulate area as a target structure in canine epilepsy. The subtle changes only might be explained by the short duration of epilepsy, small sample sizes, and the higher variability in canine brain anatomy. Furthermore, all included dogs showed generalized tonic-clonic seizures, possibly affected by generalized epilepsy syndrome, which are also associated with less pronounced DTI changes in humans than focal epilepsy syndromes.

Within-person changes in the aging white matter microstructure and their modifiers: A meta-analysis and systematic review of longitudinal diffusion tensor imaging studies

Abstract This meta-analysis and systematic review synthesized data from 30 longitudinal diffusion tensor imaging (DTI) studies on the magnitude, direction, spatial patterns, and modifiers of naturally occurring within-person changes in healthy adult white matter (WM) microstructure. Results revealed: (1) significant within-person declines in fractional anisotropy (FA) in the whole WM (d = -0.12), genu (d = -0.16), and splenium (d = -0.13); (2) greater declines in FA associated with older age, longer follow-up times, and female sex; (3) a possible yet inconclusive vulnerability of late-myelinating WM (the “development-to-degeneration” gradient); and (4) factors decelerating (e.g., physical activity and social activities) and accelerating (e.g., vascular risk factors, biomarkers for Alzheimer’s disease, and alcohol consumption) age-related FA changes. Our findings encourage the consideration of WM as a new target for treatments and interventions against cognitive decline and lay the foundation for studying the plastic and regenerative potential of adult WM in clinical trials. Individual differences in WM changes could aid in the preclinical diagnosis of dementia, opening a window for earlier, more effective treatments.

Features of changes in fractional anisotropy of different brain parts during the progression of Parkinson's disease

BACKGROUND: Parkinson's disease is a neurodegenerative disease, in second place in terms of incidence in the world after Alzheimer's disease. It is currently believed that the presymptomatic stages of Parkinson's disease are mainly associated with degeneration of the subcortical and vegetetive nervous systems, and lesions of the cerebral cortex appear on later stages of the disease, however, it is of interest to study in more detail the involvement of the pathways of the brain in the pathological process in depending the disease progression.&#x0D; OBJECTIVE: to study features of damage to the brain pathways during the progression of Parkinson's disease by magnetic resonance tractography.&#x0D; MATERIAL AND METHODS: 88 patients with Parkinson's disease were examined (stage II disease — 42 people, stage III — 46 people according to the Hoehn and Yahr scale). The control group consisted of 35 people who did not differ in gender. All patients included in the study underwent a neurological examination, as well as magnetic resonance imaging of the brain with diffusion tensor imaging.&#x0D; RESULTS: We found that with increasing stage of Parkinson's disease, there was a significant increase in fractional anisotropy in the hippocampus, insular cortex, and inferior and superior temporal sulcus cortex in patients with Parkinson's disease; we also noted a significant decrease in putamen fractional anisotropy.&#x0D; CONCLUSION: the tractography study of the brain pathways during disease progression is a promising method that allows us to clarify in the pathogenesis of Parkinson's disease, including the role of extra-nigral pathology in the development of some non-motor disorders.

Hippocampus‐associated tract degradation follows differential DTI patterns and is influenced by amyloid in MCI patients

AbstractBackgroundDiffusion tensor imaging (DTI) has been leveraged to understand microstructural alterations to limbic and cortico‐cortical tracts in Alzheimer’s disease (AD). However, investigation into the key changes and patterns of fractional anisotropy (FA) and mean diffusivity (MD) metrics in the early stages of MCI has not been widely investigated. This study aimed to establish whether the early DTI white matter tract changes in MCI patients are decoupled and whether amyloid positivity (Aβ+/Aβ‐) is associated with early tract degradation.Method171 participants (103 MCI &amp; 73 CN) were recruited from the AD Neuroimaging Initiative (ADNI; adni.loni.usc.edu) database. For each participant, FA and MD maps were obtained at their baseline scan and voxel wise analysis was carried out using FSL (https://fsl.fmrib.ox.ac.uk/fsl/) and Tract‐Based Spatial Statistics (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS). Students t‐tests were conducted on the FA and MD changes in hippocampal WM tracts, previously identified as areas of potential early degradation. Comparisons between CN and MCI groups were made along Aβ+ and Aβ‐ groups.ResultWe found evidence for WM degradation, indicated by lower FA scores in MCI participants compared with controls, in the specific regions of interest of the fornix (p = 0.004) and tapetum (p = 0.012). Mean diffusivity was increased in the MCI group compared to CN in areas of the fornix (p &lt; 0.001), consistent with FA alterations, yet differed from areas identified in FA changes owing to changes in the uncinate fasciculus (p = 0.022) and cingulum (p = 0.003). Comparison of DTI metrics in the fornix between amyloid status groups revealed that Aβ+ participants had significantly lower FA compared to Aβ‐ participants (p = 0.047), but MD did not significantly differ.ConclusionThese results confirm the notion that WM tract integrity degradation in the tract apparatus surrounding the hippocampus occur early in the AD trajectory. However, results indicate that FA alterations occur in different patterns to that of MD and that amyloid may influence these patterns. This supports the idea that efforts to develop therapeutics which maintain WM tract integrity early may be key to slowing AD progression.

Altered Endogenous Expression of Alzheimer’s Risk Genes impacts Neural Morphology in a Large Cohort of Healthy study Participants

AbstractBackgroundDysregulation of white matter tracts (WMTs) in the brain is a common feature of Alzheimer’s Disease (AD) and is associated with declining cognitive function. Two neuroimaging measures, Fractional Anisotropy (FA) and isometric volume fraction (ISOVF) represent WM integrity through quantifying organization of axon bundles and changes in extracellular fluid within the fiber tracts (as occurs in inflammation or degeneration) respectively. Previous work examining the genetic basis of WMT changes in AD largely focused on SNP‐level associations. Here, we leverage transcriptome wide association studies (TWAS) and Mendelian randomization (MR) to interrogate the expression‐mediated influence of AD genes on WMT integrity.MethodWe first perform a multi‐tissue TWAS for AD by applying JTI‐PrediXcan to summary statistics from the largest AD GWAS meta‐analysis (Bellenguez, 2022). This approach leverages tissue‐specific eQTL models trained on data from the Genotype‐Tissue Expression project and enriched via Joint Tissue imputation to identify associations between genetically regulated gene expression (GReX) and AD (Barbeira, 2018). We apply prediction performance thresholds and correct for multiple testing. We perform similar TWAS using JTI‐PrediXcan on neuroimaging data from 33,000 participants in the UK Biobank to identify tissue‐specific associations between GReX and WMTs (FA and ISOVF) (Smith, 2021). We integrate these studies to identify AD‐associated genes associated with changes in FA or ISOVF. We quantify the GReX causal effect on WMTs through the MR protocol, MR‐JTI, which assumes gene expression as the exposure (Zhou, 2020).ResultOur AD TWAS identifies 59 genes. 14 occur at the APOE locus and we replicate 2 additional genes prioritized in the initial GWAS. FUMA analysis of our gene set implicates the brain as the primary tissue of downregulation (Watanabe, 2017). Neuroimaging analysis of these genes highlights 5 WMTs and 2 genes. GReX of CR1 is causally associated with ISOVF of the right acoustic radiation and superior longitudinal fasciculus. GReX of INO80E is causally associated with FA of the left inferior longitudinal fasciculus and the bilateral superior thalamic radiations.ConclusionBy integrating TWAS of AD and neuroimaging data, we identify multiple significant, tissue‐specific, causal associations between AD‐associated GReX and the integrity of key WMTs associated with cognitive function.

Baseline Amyloid and Tau Deposition Predict Distinct Patterns of Longitudinal White Matter Degeneration: A Diffusion MRI Investigation

AbstractBackgroundNeuritic plaques with fibrillar beta‐amyloid (Aβ) peptides and tau‐protein neurofibrillary tangles are hallmark features of Alzheimer’s disease (AD) pathology. While concomitant differences in white matter (WM) integrity were found in association with Aβ deposition or tau pathology, a unique effect of each pathology on WM integrity remains unknown. In this study, we examined the unique effects of AD pathologies on WM integrity both cross‐sectionally and longitudinally.MethodA total of 334 participants (188 cognitively normal (CN), 114 mild cognitive impairment, and 32 AD) was selected from the ADNI database, based on the availability of two timepoints of diffusion MRI (dMRI) data, and baseline amyloid and tau PET data. The dMRI data were processed using FSL’s TBSS pipeline to quantify the degree of fractional anisotropy (FA) and annualized FA change maps were created to measure voxel‐wise WM change over time. Baseline global amyloid SUVR values were converted to a centiloid scale. Baseline tau SUVRs were evaluated by Braak staging (I‐entorhinal, II‐hippocampal, III/IV‐limbic, V/VI‐neocortex). The associations between AD pathologies and cross‐sectional and longitudinal WM integrity were assessed by FSL’s randomise and cluster‐level correction, controlling for age and sex.ResultCross‐sectionally, baseline tau burden in Braak stages I, III/IV, and V/VI related to lower WM integrity, independent of Aβ, while there was no association between baseline Aβ and WM integrity, independent of tau. Longitudinally, limbic and neocortical tau at baseline uniquely predicted WM integrity loss across widespread regions, including left superior longitudinal fasciculus and the body and splenium of corpus callosum. Moreover, baseline Aβ burden significantly related to WM integrity loss across widespread regions, only when entorhinal and hippocampal tau was controlled for. Similar, but weaker, patterns of the associations between baseline AD pathology and longitudinal WM integrity loss were also found only within CN group.ConclusionThese findings suggest distinctive associations between AD pathology and WM degeneration such that Aß exerts widespread deleterious effects on WM integrity primarily early in AD pathophysiology, whereas, once spreading to the neocortex, tau burden drives WM neurodegeneration. The distinctive downstream pathways associated with each AD pathology may underlie differential cognitive profiles across the disease stages.

The Effects of Sex and APOE4 Genotype on Longitudinal Changes in White Matter Integrity Differ by Diagnostic Group Along the Spectrum of Alzheimer’s Disease

AbstractBackgroundSex and APOE ε4 (APOE4) are well‐established risk factors for Alzheimer’s disease (AD), with female ε4‐carriers at greatest risk. Uncovering the neurobiological substrates of sex and genetic effects in AD is critical to improve prevention, intervention, and treatment monitoring. While changes to white matter (WM) integrity are commonly noted in the progression of AD, it is unclear if these changes are further modulated by sex and APOE4 status. In the current study, we examined the effects of sex and APOE4 carrier status on WM integrity, both cross‐sectionally and longitudinally, across the AD continuum.MethodA total of 457 participants (233 cognitively normal (CN), 167 mild cognitive impairment (MCI), and 57 AD; 223 females; 187 APOE ε4‐carriers) was selected from the ADNI database, based on the availability two diffusion MRI (dMRI) sessions. The dMRI data were processed using FSL’s TBSS pipeline to quantify the degree of fractional anisotropy (FA). Annualized FA change maps were created to measure voxel‐wise WM change over time. The effect of sex, APOE4‐carrier status, diagnosis, and their interactions, on cross‐sectional and longitudinal WM integrity were assessed by FSL’s randomise and cluster‐level correction, controlling for age.ResultAt baseline, females exhibited greater FA than males in the fornix, right inferior fronto‐occipital fasciculus, left inferior and superior longitudinal fasciculus, while males showed greater FA in the left corticospinal tract. Additionally, there were widespread differences across the skeleton by diagnosis, with FA decreasing stepwise across the continuum (CN&gt;MCI&gt;AD). There were no APOE4‐related differences in baseline WM integrity. Longitudinally, a three‐way interaction between diagnosis, APOE4, and sex emerged within the corpus collasum, left anterior thalamic radiation, left corticospinal tract, left uncinate fasciculus, and left inferior and superior longitudinal fasciculus. Posthoc analyses revealed that within the AD group, but not CN or MCI groups, females underwent greater WM degeneration than males among nonε4‐carriers, while males showed greater WM degeneration than females among ε4‐carriers.ConclusionThese findings suggest that increased risk associated with sex and APOE4 genotype may change and interact with the progression of AD. Future studies are warranted to examine the contribution of cerebrovascular risk factors to AD progression in male ε4‐carriers.

Tau pathology relates to regional microstructural alterations of cerebral white matter in older adults with diverse cognitive spectrum

AbstractBackgroundGrowing evidences suggest that degeneration of cerebral white matter (WM) occurs in Alzheimer’s disease (AD) independently of cerebrovascular risks or injury. Previous studies using diffusion tensor imaging (DTI) have reported a loss of WM microstructural integrity in the corpus callosum (CC) and cingulum (CG) in AD dementia and mild cognitive impairment (MCI). However, only limited information is available for the relationship of in vivo AD‐specific pathologies including beta‐amyloid (Aβ) and tau accumulation with WM microstructal alterations. Thus, we aimed to examine the association between in vivo AD pathologies and microstructural integrity of the CC and CG through cross‐sectional and longitudinal approaches.MethodA total of 170 (74 cognitively normal, 58 MCI, and 38 AD dementia) older adults from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease cohort were included. All participants underwent comprehensive clinical assessment and multi‐modal brain imaging including [11C]‐Pittsburgh‐Compound‐B‐positron emission tomography (PET), 18F‐AV‐1451 PET, and DTI. The mean fractional anisotropy (FA) values were obtained for 2 regions of interests, the CC and CG on DTI. The data was analyzed using linear regression model adjusted for age, sex, APOE4 positivity, and vascular risk factor score. Regression‐based mediation analysis was also conducted to assess the mediation of tau for the relationship between Aβ and FA.ResultIn cross‐sectional analyses for baseline data, global tau deposition had a significant negative association with both CC and CG FA (β = ‐0.013, p = 0.004 and β = ‐0.011, p = 0.002), while global Aβ retention showed a negative association with only CG FA (β = ‐0.015, p = 0.004). Longitudinal analyses revealed that higher tau deposition at baseline was associated with both greater reduction of both CC and CG FA over 2 years (β = ‐0.010, p = 0.001 and β = ‐0.005, p = 0.046), whereas Aβ was associated with neither CC nor CG FA change over the period. Additional mediation analysis demonstrated that the cross‐sectional association between Aβ and CG FA was mediated by tau deposition, while there was no direct relationship between the two.ConclusionOur findings suggest that regional alterations of WM microstructural integrity in MCI and AD dementia, which occurs independently of vascular risks, are mainly related with tau pathology rather than amyloid pathology.

Total-Body Irradiation Alters White Matter Volume and Microstructural Integrity in Rhesus Macaques

Long-term survivors of brain irradiation can suffer from irreversible injury and cognitive impairment. T1-weighted and diffusion tensor magnetic resonance imaging are used to evaluate brain volumes and white matter (WM) microstructure in neurodevelopmental and neurodegenerative conditions. The goal of this study was to evaluate the long-term effects of single-dose total-body irradiation (TBI) or TBI with 5% partial-body sparing on brain volumetrics and WM integrity in macaques. We utilized MRI scans from a cohort of male rhesus macaques (age range: 3.6-22.8 years), to compare global and regional brain volumes and WM diffusion in survivors of TBI (T1w: n=137, DTI: n=121, dose range: 3.5-10 Gy) against unirradiated controls (T1w: n=48, DTI: n=38). In all ROIs, radiation affected the age-related changes in fractional anisotropy (FA); in general, FA increased across age in both groups, but to a lesser extent in the irradiated group (interaction p-values <0.01). Depending on the ROI, mean diffusivity (MD) decreased or remained the same across age in unirradiated animals, while it increased or did not change in irradiated animals. The increases in MD were driven by changes in radial diffusivity (RD) which followed similar trends across age. Axial diffusivity (AD) did not differ by irradiation status. Age-related changes in relative volumes in controls reflected normal trends in humans with increasing WM and decreasing gray matter (GM) until middle age. Cerebrospinal fluid (CSF) volume did not differ across age in controls. WM volume was lower and CSF volume was higher in young, irradiated macaques. WM volume was similar between groups and CSF volume reduced in older irradiated macaques. GM volume was unaffected by radiation. TBI results in delayed WM expansion and long-term disruption of WM integrity. Diffusion changes suggest that myelin injury in WM is a hallmark of late-delayed radiation induced brain injury.

Characterizing microstructural development in the fetal brain using diffusion MRI from 23 to 36weeks of gestation.

We utilized motion-corrected diffusion tensor imaging (DTI) to evaluate microstructural changes in healthy fetal brains during the late second and third trimesters. Data were derived from fetal magnetic resonance imaging scans conducted as part of a prospective study spanning from 2013 March to 2019 May. The study included 44 fetuses between the gestational ages (GAs) of 23 and 36weeks. We reconstructed fetal brain DTI using a motion-tracked slice-to-volume registration framework. Images were segmented into 14 regions of interest (ROIs) through label propagation using a fetal DTI atlas, with expert refinement. Statistical analysis involved assessing changes in fractional anisotropy (FA) and mean diffusivity (MD) throughout gestation using mixed-effects models, and identifying points of change in trajectory for ROIs with nonlinear trends. Results showed significant GA-related changes in FA and MD in all ROIs except in the thalamus' FA and corpus callosum's MD. Hemispheric asymmetries were found in the FA of the periventricular white matter (pvWM), intermediate zone, and subplate and in the MD of the ganglionic eminence and pvWM. This study provides valuable insight into the normal patterns of development of MD and FA in the fetal brain. These changes are closely linked with cytoarchitectonic changes and display indications of early functional specialization.

MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up.

There is mounting evidence of the long-term effects of COVID-19 on the central nervous system, with patients experiencing diverse symptoms, often suggesting brain involvement. Conventional brain MRI of these patients shows unspecific patterns, with no clear connection of the symptomatology to brain tissue abnormalities, whereas diffusion tensor studies and volumetric analyses detect measurable changes in the brain after COVID-19. Diffusion MRI exploits the random motion of water molecules to achieve unique sensitivity to structures at the microscopic level, and new sequences employing generalized diffusion encoding provide structural information which are sensitive to intravoxel features. In this observational study, a total of 32 persons were investigated: 16 patients previously hospitalized for COVID-19 with persisting symptoms of post-COVID condition (mean age 60 years: range 41-79, all male) at 7-month follow-up and 16 matched controls, not previously hospitalized for COVID-19, with no post-COVID symptoms (mean age 58 years, range 46-69, 11 males). Standard MRI and generalized diffusion encoding MRI were employed to examine the brain white matter of the subjects. To detect possible group differences, several tissue microstructure descriptors obtainable with the employed diffusion sequence, the fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, microscopic anisotropy, orientational coherence (Cc) and variance in compartment's size (CMD) were analysed using the tract-based spatial statistics framework. The tract-based spatial statistics analysis showed widespread statistically significant differences (P < 0.05, corrected for multiple comparisons using the familywise error rate) in all the considered metrics in the white matter of the patients compared to the controls. Fractional anisotropy, microscopic anisotropy and Cc were lower in the patient group, while axial diffusivity, radial diffusivity, mean diffusivity and CMD were higher. Significant changes in fractional anisotropy, microscopic anisotropy and CMD affected approximately half of the analysed white matter voxels located across all brain lobes, while changes in Cc were mainly found in the occipital parts of the brain. Given the predominant alteration in microscopic anisotropy compared to Cc, the observed changes in diffusion anisotropy are mostly due to loss of local anisotropy, possibly connected to axonal damage, rather than white matter fibre coherence disruption. The increase in radial diffusivity is indicative of demyelination, while the changes in mean diffusivity and CMD are compatible with vasogenic oedema. In summary, these widespread alterations of white matter microstructure are indicative of vasogenic oedema, demyelination and axonal damage. These changes might be a contributing factor to the diversity of central nervous system symptoms that many patients experience after COVID-19.

Changes in cardiovascular health and white matter integrity with aerobic exercise, cognitive and combined training in physically inactive healthy late-middle-aged adults: the “Projecte Moviment” randomized controlled trial

IntroductionThis is a 12-weeks randomized controlled trial examining the effects of aerobic exercise (AE), computerized cognitive training (CCT) and their combination (COMB). We aim to investigate their impact on cardiovascular health and white matter (WM) integrity and how they contribute to the cognitive benefits.Methods109 participants were recruited and 82 (62% female; age = 58.38 ± 5.47) finished the intervention with > 80% adherence. We report changes in cardiovascular risk factors and WM integrity (fractional anisotropy (FA); mean diffusivity (MD)), how they might be related to changes in physical activity, age and sex, and their potential role as mediators in cognitive improvements.ResultsA decrease in BMI (SMD = − 0.32, p = 0.039), waist circumference (SMD = − 0.42, p = 0.003) and diastolic blood pressure (DBP) (SMD = − 0.42, p = 0.006) in the AE group and a decrease in BMI (SMD = − 0.34, p = 0.031) and DBP (SMD = − 0.32, p = 0.034) in the COMB group compared to the waitlist control group was observed. We also found decreased global MD in the CCT group (SMD = − 0.34; p = 0.032) and significant intervention-related changes in FA and MD in the frontal and temporal lobes in the COMB group.ConclusionsWe found changes in anthropometric measures that suggest initial benefits on cardiovascular health after only 12 weeks of AE and changes in WM microstructure in the CCT and COMB groups. These results add evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them.Clinical Trial RegistrationClinicalTrials.gov NCT031123900.