White Matter Alterations In Patients Research Articles

Interhemispheric and Corticothalamic White-Matter Dysfunction Underlies Affective Morbidity and Impaired Pain Modulation in Chronic Pain.

Although patients with chronic pain show behavioral signs of impaired endogenous pain modulation, responsible cerebral networks have yet to be anatomically delineated. We used diffusion tensor imaging (DTI) to examine the white-matter alterations in patients with chronic pain compared with healthy subjects. We further measured thermal pain modulatory responses using the offset analgesia (OA) paradigm. We tested whether the white-matter indices be associated with psychophysical parameters reflecting morbidity and modulatory responses of pain in patients, and whether they could serve as diagnostic biomarkers of chronic pain. Twenty-six patients with chronic pain and 18 age- and gender-matched healthy controls were enrolled. After completing psychophysical questionnaires, they underwent OA measurement and whole-brain DTI in a 3 Tesla magnetic resonance imaging scanner. Fractional anisotropy (FA) and radial diffusivity (RD) of the white-matter were computed and compared between the groups with tract-based spatial statistics using the FMRIB Software Library (FSL) software. Correlations were sought among white-matter indices, thermal pain responses, and psychophysical parameters. The white-matter indices and OA-related parameters were tested whether they distinguish patients from controls by receiver operating characteristic analysis. During OA, patients showed a shorter latency to the maximum (maximum visual analog scale [VAS] latency, 16.0 ± 3.7 vs 18.9 ± 3.1 second [mean ± standard deviation, SD]; P = .032) but a longer latency to the minimum pain (OA latency, 15.6 ± 3.5 vs 11.1 ± 4.2 seconds; P = .004) than controls. They showed a smaller mean FA (0.44 ± 0.12 vs 0.45 ± 0.11; P = .012) and a larger mean RD of the global white-matter (0.00057 ± 0.00002 vs 0.00056 ± 0.00002; P = .038) than controls, at specific areas including the corpus callosum, anterior thalamic radiation, and forceps major. FA of the splenium of the corpus callosum was associated with maximum VAS latency (r = 0.493) and OA latency (r = -0.552). The Pain Catastrophizing Scale scores showed strong negative correlations with FA across those specific areas (r = -0.405). Those latencies during OA and white-matter metrics distinguished patients from controls (P < .05). Patients with chronic pain showed dysfunction of the white matter concerned with interhemispheric communication of sensorimotor information as well as descending corticothalamic modulation of pain in association with affective morbidity and altered temporal dynamics of pain perception. We suggest that an impaired interhemispheric modulation of pain, through the corpus callosum, might be a novel cerebral mechanism in chronification of pain.

Cerebral blood flow and white matter alterations in adults with phenylketonuria

BackgroundPhenylketonuria (PKU) represents a congenital metabolic defect that disrupts the process of converting phenylalanine (Phe) into tyrosine. Earlier investigations have revealed diminished cognitive performance and changes in brain structure and function (including the presence of white matter lesions) among individuals affected by PKU. However, there exists limited understanding regarding cerebral blood flow (CBF) and its potential associations with cognition, white matter lesions, and metabolic parameters in patients with PKU, which we therefore aimed to investigate in this study. MethodArterial spin labeling perfusion MRI was performed to measure CBF in 30 adults with early-treated classical PKU (median age 35.5 years) and 59 healthy controls (median age 30.0 years). For all participants, brain Phe levels were measured with 1H spectroscopy, and white matter lesions were rated by two neuroradiologists on T2 weighted images. White matter integrity was examined with diffusion tensor imaging (DTI). For patients only, concurrent plasma Phe levels were assessed after an overnight fasting period. Furthermore, past Phe levels were collected to estimate historical metabolic control. On the day of the MRI, each participant underwent a cognitive assessment measuring IQ and performance in executive functions, attention, and processing speed. ResultsNo significant group difference was observed in global CBF between patients and controls (F (1, 87) = 3.81, p = 0.054). Investigating CBF on the level of cerebral arterial territories, reduced CBF was observed in the left middle and posterior cerebral artery (MCA and PCA), with the most prominent reduction of CBF in the anterior subdivision of the MCA (F (1, 87) = 6.15, p = 0.015, surviving FDR correction). White matter lesions in patients were associated with cerebral blood flow reduction in the affected structure. Particularly, patients with lesions in the occipital lobe showed significant CBF reductions in the left PCA (U = 352, p = 0.013, surviving FDR correction). Additionally, axial diffusivity measured with DTI was positively associated with CBF in the ACA and PCA (surviving FDR correction). Cerebral blood flow did not correlate with cognitive performance or metabolic parameters. ConclusionThe relationship between cerebral blood flow and white matter indicates a complex interplay between vascular health and white matter alterations in patients with PKU. It highlights the importance of considering a multifactorial model when investigating the impact of PKU on the brain.

White matter alterations in pediatric brainstem glioma: An national brain tumor registry of China study.

BackgroundPrevious studies have identified alterations in structural connectivity of patients with glioma. However, white matter (WM) integrity measured by diffusion kurtosis imaging (DKI) in pediatric patients with brainstem glioma (BSG) was lack of study. Here, the alterations in WM of patients with BSG were assessed through DKI analyses.Materials and methodsThis study involved 100 patients with BSG from the National Brain Tumor Registry of China (NBTRC) and 50 age- and sex-matched healthy controls from social recruitment. WM tracts were segmented and reconstructed using U-Net and probabilistic bundle-specific tracking. Next, automatic fiber quantitative (AFQ) analyses of WM tracts were performed using tractometry module embedded in TractSeg.ResultsWM quantitative analysis identified alterations in DKI-derived values in patients with BSG compared with healthy controls. WM abnormalities were detected in the projection fibers involved in the brainstem, including corticospinal tract (CST), superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP) and inferior cerebellar peduncle (ICP). Significant WM alterations were also identified in commissural fibers and association fibers, which were away from tumor location. Statistical analyses indicated the severity of WM abnormality was statistically correlated with the preoperative Karnofsky Performance Scale (KPS) and symptom duration of patients respectively.ConclusionThe results of this study indicated the widely distributed WM alterations in patients with BSG. DKI-derived quantitative assessment may provide additional information and insight into comprehensively understanding the neuropathological mechanisms of brainstem glioma.

Dose-dependent early white matter alterations in patients with brain metastases after radiotherapy.

Previous diffusion tensor imaging (DTI) studies have mainly focused on dose-dependent white matter (WM) alterations 1month to 1year after radiation therapy (RT) with a tract-average method. However, WM alterations immediately after RT are subtle, resulting in early WM alterations that cannot be detected by tract-average methods. Therefore, we performed a study with an along-tract method in patients with brain metastases to explore the early dose-response pattern of WM alterations after RT. Sixteen patients with brain metastases underwent DTI before and 1-3days after brain RT. DTI metrics, such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were calculated. Along-tract statistics were then used to resample WM fibre streamlines and generate a WM skeleton fibre tract. DTI metric alterations (post_RT-pre_RT DTI metrics) and the planned doses (max or mean doses) were mapped to 18 WM tracts. A linear fixed model was performed to analyse the main effect of dose on DTI metric alterations. AD alterations in the left hemispheric uncinated fasciculus (UNC_L) were associated with max doses, in which decreased AD alterations were associated with higher doses. Our findings may provide pathological insight into early dose-dependent WM alterations and may contribute to the development of max dose-constrained RT techniques to protect brain microstructure in the UNC_L.

Microstructural white matter changes in chronic migraine patients with liver-yang hyperactivity and qi-blood deficiency syndrome: a diffusion tensor imaging study.

White matter alterations in patients with chronic migraine (CM) have been reported. Traditional Chinese medicine (TCM) syndromes are clinical syndromes proposed by TCM doctors based on long-term clinical observation and classification of the clinical symptoms and signs of CM patients. This study aimed to analyze the whole-brain diffusion tensor imaging (DTI) data of CM patients with different types of TCM syndromes. Sixteen CM patients diagnosed with liver-yang hyperactivity (LH) syndrome and 16 CM patients with qi-blood deficiency (QD) syndrome were recruited in this study. Thirty-one healthy controls (HCs) were also enrolled. All subjects underwent DTI and T1-weighted MRI acquisition. Thirty HCs and 30 CM patients (LH group: n = 15; QD group: n = 15) were included in the final analysis. No significant difference was observed in the DTI indexes between CM patients and HCs, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The mean FAs of the left tapetum and the mean MD values for the right medial lemniscus and the right inferior cerebellar peduncle were significantly different in the LH and HC groups. The mean AD values for the right cingulate gyrus and the left uncinate fasciculus, as well as the mean RD for the right inferior cerebellar peduncle and the left tapetum, were also significantly different between these two groups. CM patients with LH and QD syndrome showed altered FA and diffusivity in comparison to healthy controls, suggesting that there may be significant white matter microstructural alterations in these patients.

Relationship of white matter hyperintensities with clinical features of seizures in patients with epilepsy.

Although epilepsy is primarily known as a cortical disorder, there is growing body of research demonstrating white matter alterations in patients with epilepsy. To investigate the prevalence of white matter hyperintensities (WMH) and its association with seizure characteristics in patients with epilepsy. The prevalence of WMH in 94 patients with epilepsy and 41 healthy controls were compared. Within the patient sample, the relationship between the presence of WMH and type of epilepsy, frequency of seizures, duration of disease and the number of antiepileptic medications were investigated. The mean age and sex were not different between patients and healthy controls (p>0.2). WMH was present in 27.7% of patients and in 14.6% of healthy controls. Diagnosis of epilepsy was independently associated with the presence of WMH (ß=3.09, 95%CI 1.06-9.0, p=0.039). Patients with focal epilepsy had higher prevalence of WMH (35.5%) than patients with generalized epilepsy (14.7%). The presence of WMH was associated with older age but not with seizure characteristics. WMH is more common in patients with focal epilepsy than healthy controls. The presence of WMH is associated with older age, but not with seizure characteristics.

Widespread White Matter Alterations in Patients With Visual Snow Syndrome.

Background: Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant binocular flickering or pixilation of the whole visual field. The underlying neurophysiological and structural alterations remain elusive.Methods: In this study, we included patients (final n = 14, five dropouts; five females, mean age: 32 years) with visual snow syndrome (VSS) and age- and sex-matched controls (final n = 20, 6 dropouts, 13 females, mean age: 28.2 years). We applied diffusion tensor imaging to examine possible white matter (WM) alterations in patients with VSS.Results: The patient group demonstrated higher (p-corrected < 0.05, adjusted for age and sex) fractional anisotropy (FA) and lower mean diffusivity (MD) and radial diffusivity (RD) compared to controls. These changes were seen in the prefrontal WM (including the inferior fronto-occipital fascicle), temporal and occipital WM, superior and middle longitudinal fascicle, and sagittal stratum. When additionally corrected for migraine or tinnitus—dominant comorbidities in VSS—similar group differences were seen for FA and RD, but less pronounced.Conclusions: Our results indicate that patients with VSS present WM alterations in parts of the visual cortex and outside the visual cortex. As parts of the inferior fronto-occipital fascicle and sagittal stratum are associated with visual processing and visual conceptualisation, our results suggest that the WM alterations in these regions may indicate atypical visual processing in patients with VSS. Yet, the frequent presence of migraine and other comorbidities such as tinnitus in VSS makes it difficult to attribute WM disruptions solely to VSS.

White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder.

ObjectiveRegarding the neuroinflammatory theory of major depressive disorder (MDD), little is known about the effect of pro-inflammatory cytokines on white matter (WM) changes in MDD. We aimed to investigate the relationship between pro-inflammatory cytokines and WM alterations in patients with MDD.MethodsTwenty-two patients with MDD and 22 healthy controls (HC) were evaluated for brain imaging and pro-inflammatory cytokines including interleukin (IL)-1b, IL-6, IL-8, interferon-g and tumor necrosis factor (TNF)-α. Tract-based spatial statistics and FreeSurfer were used for brain image analysis.ResultsThe levels of TNF-α and IL-8 were significantly higher in the MDD group than in HC. Compared to HC, lower fractional anisotropy (FA), and higher median diffusivity (MD) and radial diffusivity (RD) values were found in the MDD group for several WM regions. Voxel-wise correlation analysis showed that the level of TNF-α was negatively correlated with FA, and positively correlated with MD and RD in the left body and genu of the corpus callosum, left anterior corona radiata, and left superior corona radiata.ConclusionOur findings suggest that TNF-α may play an important role in the WM alterations in depression, possibly through demyelination.

Neurological Soft Signs Are Associated With Altered White Matter in Patients With Schizophrenia.

Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.

Hybrid diffusion imaging reveals altered white matter tract integrity and associations with symptoms and cognitive dysfunction in chronic traumatic brain injury

The detection and association of in vivo biomarkers in white matter (WM) pathology after acute and chronic mild traumatic brain injury (mTBI) are needed to improve care and develop therapies. In this study, we used the diffusion MRI method of hybrid diffusion imaging (HYDI)to detect white matter alterations in patients with chronic TBI (cTBI). 40 patients with cTBI presenting symptoms at least three months post injury, and 17 healthy controls underwent magnetic resonance HYDI. cTBI patients were assessed with a battery of neuropsychological tests. A voxel-wise statistical analysis within the white matter skeleton was performed to study between group differences in the diffusion models. In addition, a partial correlation analysis controlling for age, sex, and time after injury was performed within the cTBI cohort, to test for associations between diffusion metrics and clinical outcomes. The advanced diffusion modeling technique of neurite orientation dispersion and density imaging (NODDI) showed large clusters of between-group differences resulting in lower values in the cTBI across the brain, where the single compartment diffusion tensor model failed to show any significant results. However, the diffusion tensor model appeared to be just as sensitive in detecting self-reported symptoms in the cTBI population using a within-group correlation. To the best of our knowledge this study provides the first application of HYDI in evaluation of cTBI using combined DTI and NODDI, significantly enhancing our understanding of the effects of concussion on white matter microstructure and emphasizing the utility of full characterization of complex diffusion to diagnose, monitor, and treat brain injury.

The role of diffusion tensor imaging in idiopathic normal pressure hydrocephalus: A literature review.

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome that comprises a triad of gait disturbance, dementia and urinary incontinence, associated with ventriculomegaly in the absence of elevated intraventricular cerebrospinal fluid (CSF) pressure. It is important to identify patients with iNPH because some of its clinical features may be reversed by the insertion of a CSF shunt. The diagnosis is based on clinical history, physical examination and brain imaging, especially magnetic resonance imaging (MRI). Recently, some papers have investigated the role of diffusion tensor imaging (DTI) in evaluating white matter alterations in patients with iNPH. DTI analysis in specific anatomical regions seems to be a promising MR biomarker of iNPH and could also be used in the differential diagnosis from other dementias. However, there is a substantial lack of structured reviews on this topic. Thus, we performed a literature search and analyzed the most recent and pivotal articles that investigated the role of DTI in iNPH in order to provide an up-to-date overview of the application of DTI in this setting. We reviewed studies published between January 2000 and June 2020. Thirty-eight studies and four reviews were included. Despite heterogeneity in analysis approaches, the majority of studies reported significant correlations between DTI and clinical symptoms in iNPH patients, as well as different DTI patterns in patients with iNPH compared to those with Alzheimer or Parkinson diseases. It remains to be determined whether DTI could predict the success after CSF shunting.

Detection of microstructural white matter alterations in functional gastrointestinal disorders assessed by diffusion kurtosis imaging.

Background and AimWe evaluated whether diffusion kurtosis and tensor imaging (DKI/DTI) could reveal microstructural alterations in the brains of patients with functional gastrointestinal disorders (FGIDs), and whether imaging findings were correlated with health‐related quality of life (HRQOL).MethodsTwelve patients with FGIDs fulfilling the Rome IV criteria, and seven healthy controls were examined using a 3 T magnetic resonance (MR) scanner. Tract‐based spatial statistics and regions of interest analyses were performed to compare the mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) between patients with FGIDs versus controls. HRQOL was assessed in patients with FGIDs using the eight‐item short form of the Medical Outcome Study Questionnaire (SF‐8) and the Gastrointestinal Symptom Rating Scale.ResultsPatients with FGIDs had extensive, widespread regions of reduced MD in the white matter in comparison with healthy controls, whereas no significant differences were observed in MK and FA. No significant differences in deep gray matter for the MK, FA, and MD values were observed between patients with FGIDs and controls. In patients with FGIDs, the FA values in the globus pallidus had a significant and negative correlation with SF‐8 (a mental component summary) (r = −0.797, P = 0.01 uncorrected for multiple comparisons).ConclusionsDKI/DTI can help identify microstructural white matter alterations in patients with FGIDs. The FA values in the globus pallidus may be useful for a severity assessment of FGIDs.

White matter microstructural organizations in patients with severe treatment-resistant schizophrenia: A diffusion tensor imaging study

Previous diffusion tensor imaging (DTI) studies have reported white matter alterations in patients with schizophrenia. Notably, one third of this population does not respond to first-line antipsychotics and is thus referred to as treatment-resistant schizophrenia (TRS). Despite potentially distinct neural bases between TRS and non-TRS, few studies have compared white matter integrity between these groups. In order to reflect clinical picture of TRS, we enrolled TRS patients who had severe symptoms. According to the consensus criteria for TRS. TRS was defined by severe positive symptomatology despite optimal antipsychotic treatment. Fractional anisotropy (FA), an index of white matter integrity, was examined by DTI and analyzed with tract-based spatial statistics in 24 TRS patients (mean PANSS = 108.9), 28 non-TRS patients (mean PANSS = 50.0), and 27 healthy controls (HCs) for group comparison. Additionally, correlation analyses were conducted between FA values and symptomatology. The TRS group had lower FA values in multiple tracts (cerebral peduncle, corona radiata, corpus callosum, external and internal capsules, posterior thalamic radiation, sagittal stratum, superior longitudinal fasciculus, tapetum, and uncinate fasciculus) compared to the HC group as well as the non-TRS group (p < .05; family-wise error-corrected), while no differences were found between the non-TRS and HC groups. In the TRS group, FA values in most of the tracts (other than the left anterior limb of internal capsule, left cerebral peduncle, and right uncinate fasciculus) were negatively correlated with the Positive and Negative Syndrome Scale total scores, and negative and general symptom scores. No such relationships were found in the non-TRS group. The identified white matter integrity deficits may reflect the pathophysiology of TRS.

Sensorimotor and pain-related alterations of the gray matter and white matter in Type 2 diabetic patients with peripheral neuropathy.

Although diabetic peripheral neuropathy (DPN) has long been considered a disease of the peripheral nervous system, recent neuroimaging studies have shown that alterations in the central nervous system may play a crucial role in its pathogenesis. Here, we used surface‐based morphometry (SBM) and tract‐based spatial statistics (TBSS) to investigate gray matter (GM) and white matter (WM) differences between patients with DPN (n = 67, 44 painless and 23 painful) and healthy controls (HCs; n = 88). Compared with HCs, patients with DPN exhibited GM abnormalities in the pre‐ and postcentral gyrus and in several deep GM nuclei (caudate, putamen, medial pallidum, thalamus, and ventral nuclear). They also exhibited altered WM tracts (corticospinal tract, spinothalamic tract, and thalamocortical projecting fibers). These findings suggest impaired motor and somatosensory pathways in DPN. Further, patients with DPN (particularly painful DPN) exhibited morphological differences in the cingulate, insula, prefrontal cortex, and thalamus, as well as impaired WM integrity in periaqueductal WM and internal and external capsules. This suggests pain‐perception/modulation pathways are altered in painful DPN. Intermodal correlation analyses found that the morphological indices of the brain regions identified by the SBM analysis were significantly correlated with the fractional anisotropy of brain regions identified by the TBSS analysis, suggesting that the GM and WM alterations were tightly coupled. Overall, our study showed sensorimotor and pain‐related GM and WM alterations in patients with DPN, which might be involved in the development of DPN.

Ascending Axonal Degeneration of the Corticospinal Tract in Pure Hereditary Spastic Paraplegia: A Cross-Sectional DTI Study.

Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 age and gender matched healthy controls. DTI was performed using a 3 T clinical scanner with whole brain tract-based spatial statistical (TBSS) analysis of the obtained fractional anisotropy (FA) data as well as a region-of-interest (ROI)-based analysis of affected tracts including the cervical spinal cord. We further conducted correlation analyses between DTI data and clinical characteristics. Results: TBSS analysis in HSP patients showed significantly decreased fractional anisotropy of the corpus callosum and the corticospinal tract compared to healthy controls. ROI-based analysis confirmed significantly lower FA in HSP compared to controls in the internal capsule (0.77 vs. 0.80, p = 0.048), the corpus callosum (0.84 vs. 0.87, p = 0.048) and the cervical spinal cord (0.72 vs. 0.79, p = 0.003). FA values of the cervical spinal cord significantly correlated with disease duration. Conclusion: DTI metrics of the corticospinal tract from the internal capsule to the cervical spine suggest microstructural damage and axonal degeneration of motor neurons. The CST at the level of the cervical spinal cord is thereby more severely affected than the intracranial part of the CST, suggesting an ascending axonal degeneration of the CST. Since there is a significant correlation with disease duration, FA may serve as a future progression marker for assessment of the disease course in HSP.

White matter alterations in adult with autism spectrum disorder evaluated using diffusion kurtosis imaging

Autism spectrum disorder (ASD) is related to impairment in various white matter (WM) pathways. Utility of the recently developed two-compartment model of diffusion kurtosis imaging (DKI) to analyse axial diffusivity of WM is restricted by several limitations. The present study aims to validate the utility of model-free DKI in the evaluation of WM alterations in ASD and analyse the potential relationship between DKI-evident WM alterations and personality scales. Overall, 15 participants with ASD and 15 neurotypical (NT) controls were scanned on a 3T magnetic resonance (MR) scanner, and scores for autism quotient (AQ), systemising quotient (SQ) and empathising quotient (EQ) were obtained for both groups. Multishell diffusion-weighted MR data were acquired using two b-values (1000 and 2000s/mm2). Differences in mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) between the groups were evaluated using tract-based spatial statistics (TBSS). Finally, the relationships between the kurtosis indices and personality quotients were examined. The ASD group demonstrated significantly lower AK in the body and splenium of corpus callosum than the NT group; however, no other significant differences were identified. Negative correlations were found between AK and AQ or SQ, predominantly in WM areas related to social-emotional processing such as uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior and superior longitudinal fasciculi. Model-free DKI and its indices may represent a novel, objective method for detecting the disease severity and WM alterations in patients with ASD.

A preliminary report of longitudinal white matter alterations in patients with end-stage renal disease: A three-year diffusion tensor imaging study.

PurposeEnd-stage renal disease (ESRD) patients exhibit silent white-matter alterations after long-term hemodialysis, which may be due to ESRD itself or the hemodialysis. The purpose of this study was to investigate the longitudinal white-matter alterations in the ESRD patients under 3-year long-term hemodialysis using voxel-wise analysis of diffusion tensor imaging (DTI).Materials and methods15 ESRD patients and 15 age-matched healthy controls participated in this study. Due to the development of abnormal brain lesions in some cases, 13 ESRD patients and 13 age-matched healthy controls were enrolled and underwent cognitive function assessment and DTI acquisition at two-time points separated by 3 years. Voxel-based analysis was performed to globally detect white-matter alterations between the two groups as well as between the two scans within the two groups.ResultsIn the ESRD patients, diffusivity indices were significantly increased and the fractional anisotropy was significantly decreased in both scans, as compared with healthy controls. Longitudinal comparisons showed significant white-matter alterations in healthy controls in three years, but little or no significant alterations were noted in the ESRD patients after additional 3-year hemodialysis.ConclusionPoorer white matter integrity and cognitive function are noted in ESRD patients and the toxic effect of ESRD may be the major factor of white matter alterations.

A longitudinal fixel-based analysis of white matter alterations in patients with Parkinson's disease.

Disruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease. Fifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8±6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24±2 months], and second follow-up [after a mean of 40±3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3±5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p<0.05 was considered statistically significant. Early degeneration in the splenium of corpus callosum was identified as a typical alteration of Parkinson's disease over time. At follow-up, we observed significant FDC reductions compared with baseline in white matter, noticeably in corpus callosum; tapetum; cingulum, posterior thalamic radiation, corona radiata, and sagittal stratum. We also identified significant FC decreases that reflected damage to white matter structures involved in Parkinson's disease -related pathways. Fixel-based metrics were found to relate with a deterioration of 39-item Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale and activity of daily living. A Parkinson's disease -facilitated aging effect was observed in terms of white matter disruption. This study provides a thorough fixel-based profile of longitudinal white matter alterations occurring in patients with Parkinson's disease and new evidence of FC as an important role in white matter degeneration in this setting.

Callosal and subcortical white matter alterations in schizophrenia: A diffusion tensor imaging study at multiple levels.

Diffusion tensor imaging and its distinct capability to detect micro-structural changes in vivo allows the exploration of white matter (WM) abnormalities in patients who have been diagnosed with schizophrenia; however, the results regarding the anatomical positions and degree of abnormalities are inconsistent. In order to obtain more robust and stable findings, we conducted a multi-level analysis to investigate WM disruption in a relatively large sample size (142 schizophrenia patients and 163 healthy subjects). Specifically, we evaluated the univariate fractional anisotropy (FA) in voxel level; the bivariate pairwise structural connectivity between regions using deterministic tractography as the network node defined by the Human Brainnetome Atlas; and the multivariate network topological properties, including the network hub, efficiency, small-worldness, and strength. Our data demonstrated callosal and subcortical WM alterations in patients with schizophrenia. These disruptions were evident in both voxel and connectivity levels and further supported by associations between FA values and illness duration. Based on the findings regarding topological properties, the structural network showed weaker global integration in patients with schizophrenia than in healthy subjects, while brain network hubs showed decreased functionality. We replicated these findings using an automated anatomical labeling atlas to define the network node. Our study indicates that callosal and subcortical WM disruptions are biomarkers for chronic schizophrenia.

Disrupted focal white matter integrity in autism spectrum disorder: A voxel-based meta-analysis of diffusion tensor imaging studies

BackgroundAutism spectrum disorder (ASD) is a mental disorder that has long been considered to result from brain underconnectivity. However, volumetric analysis of structural MRI data has failed to find consistent white matter alterations in patients with ASD. The present study aims to examine whether there are consistent focal white matter alterations as measured by diffusion tensor imaging (DTI) in individuals with ASD compared with typically developing (TD) individuals. MethodCoordinate-based meta-analysis was performed on 14 studies that reported fractional anisotropy (FA) alterations between individuals with ASD and TD individuals. These studies have in total 297 subjects with ASD and 302 TD subjects. ResultsActivation likelihood estimation (ALE) analysis identified two clusters of white matter regions that showed consistent reduction of FA in individuals with ASD compared with TD individuals: the left splenium of corpus callosum and the right cerebral peduncle. ConclusionsConsistent focal white matter reductions in ASD could be identified by using FA, highlighting the cerebral peduncle which is usually overlooked in studies focusing on major white matter tracts. These focal reductions in the splenium and the cerebral peduncle may be associated with sensorimotor impairments seen in individuals with ASD.