Micro-structural white matter abnormalities in new daily persistent headache: a DTI study using TBSS analysis

BackgroundDespite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)).MethodsDTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Areas showing abnormal values in the patient group were correlated (Pearson) with age, lifetime Phe values, last year median and mean Phe, concurrent Phe values in plasma, urine neurotransmitters status biomarkers, and with a processing speed task.ResultsETPKU showed bilaterally decreased MD values compared with HCs in the body and splenium of the corpus callosum, superior longitudinal fasciculus, corona radiata and in the posterior limb of the internal capsule. RD values followed a similar pattern, although decreased RD values in PKU patients were also found in the anterior limb of the internal capsule and in the cerebral peduncle. Decreased MD and RD values within the aforementioned regions had significant negative correlations with age, last year median and mean Phe and concurrent Phe values. No correlations were found with monoamines in urine or processing speed task.ConclusionsETPKU patients showed MD and RD values significantly decreased across the whole brain when compared with HCs, and this damage was associated with high Phe values and the age of patients. Despite this microstructural damage, no affectation in processing speed was observed in patients with good metabolic control. DTI-MRI sequences could be used as a technique to quantify WM damage that is difficult to be detect in T1 or T2-weighted images, but also to quantify damage of WM through the follow up of patients with poor metabolic control in prospective studies.

22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30% probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia. Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/-2years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed. Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale. Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms.

BackgroundDisrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids...

Abnormal White Matter Microstructure in Lifelong Premature Ejaculation Patients Identified by Tract–Based Spatial Statistical Analysis

Women with premenstrual syndrome (PMS) are at increased risk for depression throughout their lives. White matter (WM) microstructure and inflammatory cytokine alterations have been proposed in its etiology. To investigate whether WM, assessed using diffusion tensor imaging (DTI), and inflammatory cytokine levels are altered in PMS, and to examine the relationships between WM microstructure, inflammatory cytokines, and symptom severity. Prospective. Forty-two PMS patients and 58 healthy controls (HCs), categorized according to the daily record of severity of problems (DRSP). 3-T, echo planar imaging DTI. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured by using tract-based spatial statistics (TBSS). Venous blood was collected to measure cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Symptoms were assessed by using the DRSP. Two-sample t test or Mann-Whitney U test were used to compare the DRSP and cytokines. Abnormal DTI metrics in WM were extracted and the differences between groups were analyzed by using two sample t-tests. Spearman's correlation (r) was used to assess the relationship between DTI metrics, cytokines, and DRSP. A P-value <0.05 with FDR correction was considered statistically significant. Compared with HCs, PMS patients showed significantly lower FA in the corpus callosum and corona radiata, and significantly higher MD, AD, and RD in the corticospinal tract (CST), and significantly higher MD and RD in the anterior thalamic radiation (ATR). These differential metrics were significantly correlated with DRSP. Patients showed significantly higher IL-1β and TNF-α than HCs. Moreover, TNF-α correlated positively with MD, AD, and RD in both groups (r range, 0.256-0.315). Alterations of WM microstructure and IL-1β and TNF-α may be associated with PMS symptom severity, and TNF-α may correlate with DTI metrics of CST and ATR pathways. 1 TECHNICAL EFFICACY: Stage 2.

Increasing evidence demonstrates that there is marked damage and dysfunction in the white matter in Alzheimer's disease (AD). The present study investigates the nature of white matter damage of patients with Alzheimer's disease with diffusion tensor magnetic resonance imaging (DTI) and analyses the relationship between the white matter damage and the cognition function. DTI, as well as T1 fluid attenuated inversion recovery (FLAIR) and T2-FLAIR, was performed on probable patients of Alzheimer's disease, and sex and age matched healthy volunteers to measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, and the white matter of frontal, temporal, parietal, and occipital lobes. FA was lower in the splenium of corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer's disease than in the corresponding region from healthy controls and was strongly positive correlated with MMSE scores, whereas FA appeared no different in the anterior and posterior limbs of internal capsule, occipital lobes white matter, and the genu of corpus callosum between the patients and healthy controls. MD was significantly higher in the splenium of corpus callosum and parietal lobes white matter from patients than in that those from healthy controls and was strongly negative correlated with MMSE scores, whereas MD in the anterior and posterior limbs of internal capsule, as well as in frontal, temporal, occipital lobes white matter and the genu of corpus callosum, was not different between the patients and healthy controls. The most prominent alteration of FA and MD was in the splenium of corpus callosum. Our results suggested that white matter of patients with Alzheimer's disease was selectively impaired and the extent of damage had a strong correlation with the cognitive function, and that selective impairment reflected the cortico-cortical and cortico-subcortical disconnections in the pathomechanism of Alzheimer's disease. The values of FA and MD in white matter, especially in the splenium of corpus callosum in AD patients, might be a more appropriate surrogate marker for monitoring the disease progression.

Previous studies have proven that migraine and depression are bidirectionally linked. However, few studies have investigated white matter (WM) integrity affected by depressive symptoms in patients suffering from migraine without aura (MWoA). Forty patients with MWoA were divided into two groups according to their self-rating depression scale (SDS) score in the present study, including 20 in the SDS (+) (SDS > 49) group and 20 in the SDS (-) (SDS ≤ 49) group. Forty healthy participants were also recruited as the control group. Tract-based spatial statistics analyses with multiple diffusion tensor imaging-derived indices [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were employed collectively to investigate WM integrity between all patients with MWoA and all healthy controls, between each subgroup (SDS (-) group and SDS (+) group) and healthy controls, and between the SDS (-) and SDS (+) groups. Compared with healthy controls, decreased AD was shown in several WM tracts of the whole MWoA group, SDS (-) group and SDS (+) group. In addition, compared with the SDS (-) group, the SDS (+) group showed decreased FA and increased MD and RD, with conserved AD, including the genu, body and splenium of the corpus callosum, bilateral superior longitudinal fasciculi, the right anterior corona radiata and some other WM tracts, similar to previous findings in depression disorder. Furthermore, mean FA and RD in some of the above-mentioned WM tracts in the SDS (+) group were correlated significantly with SDS scores, including the genu and splenium of the corpus callosum, the right anterior corona radiata and the superior longitudinal fasciculi. Our results suggest that WM integrity may be affected by both depression symptoms (more sensitive as RD) and migraine (more sensitive as AD). The findings may serve as a sensitive biomarker of depression severity in MWoA.

BackgroundWe hypothesized that the integrity of white matter might be related to the severity of freezing of gait in age-related white matter changes.MethodsTwenty subjects exhibiting excessive hyperintensities in the periventricular and deep white matter were recruited. The subjects underwent the Freezing of Gait Questionnaire, computerized gait analyses, and diffusion tensor magnetic resonance imaging. Images of axial, radial and mean diffusivity, and fractional anisotropy were calculated as indices of white matter integrity and analyzed with tract-based spatial statistics.ResultsThe fractional anisotropy, mean, axial and radial diffusivity averaged across the whole white matter structure were all significantly correlated with Freezing of Gait Questionnaire scores. Regionally, a negative correlation between Freezing of Gait Questionnaire scores and fractional anisotropy was found in the left superior longitudinal fasciculus beneath the left premotor cortex, right corpus callosum, and left cerebral peduncle. The scores of the Freezing of Gait Questionnaire were positively correlated with mean diffusivity in the left corona radiata and right corpus callosum, and with both axial and radial diffusivity in the left corona radiata. The white matter integrity in these tracts (except the corpus callosum) showed no correlation with cognitive or other gait measures, supporting the specificity of those abnormalities to freezing of gait.ConclusionDivergent pathological lesions involved neural circuits composed of the cerebral cortex, basal ganglia and brainstem, suggesting that freezing of gait has a multifactorial nature.

Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age‐related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population‐based study of healthy individuals (n = 812) aged 50–66 in the Nord‐Trøndelag health survey. Semiautomated tractography and tract‐based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV‐matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.

Aim: To investigate the role of white matter integrity in the pathophysiology of tinnitus, and also to analyze the whole brain for white matter changes quantitatively by comparing tinnitus patients with healthy controls based on the affected side of the tinnitus using Tract Based Spatial Statistics (TBSS).Methods: Total of 41 right-handed tinnitus patients and 35 age-matched right-handed healthy controls were initially examined non-invasively in resting-state using the 3.0T MRI scanner. We obtained the estimated Fractional anisotropy (FA), mean diffusivity (MD), Axial Diffusivity (AD), Radial Diffusivity (RD), and Mode of Anisotropy (MO) data for each subject. TBSS was used to perform group statistical analysis of DTI data from each group.Results: Compared to controls in right-sided tinnitus patients, FA and MO were decreased, and MD was normal with decreased AD and increased RD. FA and AD showed similar decreased values (t&gt;1.5, FWEcorrected P&lt;0.05) in the right corticospinal tract, right superior longitudinal fasciculus, and right inferior fronto-occipital fasciculus. Compared to controls with left-sided tinnitus patients, FA and MO were decreased, and MD was also increased with decreased AD with increased RD in patients. MO showed significantly decreased values (t&gt;1.5, FWEcorrected P&lt;0.05) of MO in Forceps major, bilateral cingulum (especially the left), and bilateral anterior thalamic radiation. Bilaterally affected tinnitus patients showed no difference when compared to controls.Conclusion: After analyzing the whole brain for white matter changes quantitatively using TBSS, changes were observed in unilaterally affected tinnitus patients compared to controls. Our findings indicated cross-modal plasticity could have caused changes in somatosensory, audio-visual, limbic, and attention pathways.Nepal Journal of Radiology Vol.5(1-2) 2015: 1-12

The aim is to investigate whether there is a microstructural change in the white matter pathways in patients with spontaneous intracranial hypotension (SIH). Additionally, the relationship between conventional magnetic resonance imaging (MRI) findings and diffusion tensor imaging (DTI) parameters is determined. Thirty patients diagnosed with SIH and 31 control patients (between January 2019 and February 2024) were included in the case-control study. MRI findings constituting the Bern score were evaluated in contrast-enhanced brain MRI. Ten different white matter pathways were evaluated with the following DTI parameters: fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusion (AD), and radial diffusion (RD). We also examined the association between MRI findings and DTI parameters. In the cingulum, a decreased FA value (Z = -3.18, p = 0.002) was observed in patients with SIH, indicating disruption of white matter integrity and weakened synaptic transmission in this region. In the corona radiata, significant reductions were observed in both FA (Z = -5.67, p < 0.001) and AD (Z = -3.59, p < 0.001), alongside an increase in RD (Z = -4.99, p < 0.001). The concomitant increase in RD further supports the idea of potential damage to the myelin sheath, which, together with other findings, may reflect disruptions in white matter architecture that underlie the cognitive and motor deficits frequently seen in patients with SIH. In the splenium of the corpus callosum, a significant reduction in AD (Z = -3.00, p = 0.007) was also noted. In the anterior limb of the internal capsule (ALIC), both FA (Z = -4.57, p < 0.001) and AD (Z = -2.73, p = 0.012) values decreased, while RD increased (Z = -2.93, p = 0.007). These alterations suggest the involvement of motor and sensory pathways. In the posterior limb of the internal capsule (PLIC), significant reductions were found in both FA (Z = -5.59, p < 0.001) and AD (Z = -3.82, p < 0.001), along with an increase in RD (Z = -5.49, p < 0.001). In the corticospinal tract, patients with SIH exhibited a decrease in FA (Z = -4.15, p < 0.001), an increase in ADC (Z = -2.87, p = 0.008), and an increase in RD (Z = -3.73, p < 0.001). These findings represent significant microstructural changes reflecting a reduction in the integrity of motor pathways in white matter. In the middle cerebellar peduncle (MCP), patients with SIH showed increased ADC (Z = -4.78, p < 0.001) and RD (Z = -3.23, p = 0.002). Similarly, in optic radiation, there was decreased FA (Z = -4.55, p < 0.001) and AD (Z = -2.59, p = 0.018), with increased RD (Z = -2.95, p = 0.007). In the correlation analysis, positive correlations were found between suprasellar distance and AD values in both the ALIC (rs = 0.451, p = 0.012) and MCP (rs = 0.416, p = 0.022). These findings suggest that structural changes and anatomical shifts, especially in the suprasellar region, may be associated with microstructural changes in the adjacent white matter pathways. We revealed microstructural changes in white matter in SIH. The alterations in DTI parameters may suggest that the white matter microarchitecture is changed as a result of mechanical compression of the axons in the white matter pathways due to brain prolapse and venous congestion.

This study aimed to investigate the regional changes of brain white matter (WM) in DE patients using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). A total of 25 dry eye patients (PAT) and 25 healthy controls (HC) were recruited. All subjects underwent DTI and NODDI, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), isotropic volume fraction (FISO), intra-cellular volume fraction (FICVF), and orientation dispersion index (ODI) were obtained respectively. Then complete Hospital Anxiety and Depression Scale (HADS), anxiety score (AS) or depression scores (DS) were obtained. Receiver operating characteristic (ROC) curve analysis was used to evaluate the reliability of DTI and NODDI in distinguishing the two groups. DTI revealed that PAT had lower FA in both the left superior longitudinal fasciculus (LSLF) and the corpus callosum (CC), and higher MD in the LSLF, the right posterior limb of the internal capsule and the right posterior thalamic radiation. PAT had significant AD changes in regions including the genu of the CC, the right posterior limb of internal capsule, and the right splenium of the CC. From NODDI, PAT showed increased ODI in the LSLF and increased FISO in the right splenium of the CC. FICVF showed a significant decrease in the LSLF while increased in the left anterior corona radiata and the CC. Furthermore, the average values of MD and FICVF were significantly correlated with DS and AS. Hence the results of this study suggest that there are regional changes in WM in DE patients which may contribute to further understanding of the pathological mechanism of DE.

Microstructural white matter abnormalities in multiple sclerosis and neuromyelitis optica spectrum disorders: Evaluation by advanced diffusion imaging

Purpose: The aim of this study was to evaluate microstructural changes of major white matter (WM) tracts in patients with vascular cognitive impairment (VCI).Method: Diffusion tensor imaging (DTI) data were obtained from 24 subjects with subcortical ischemic vascular disease (SIVD), including 13 subjects with VCI-no dementia (VCIND) and 11 subjects with normal cognition (as a control group). A tract-based spatial statistics approach was performed to investigate WM microstructure in VCIND by integrating multiple indices including fractional anisotropy (FA) and mean diffusivity (MD), which are intra-voxel metrics, and local diffusion homogeneity (LDH), which is an inter-voxel metric.Results: The VCIND group had decreased FA and increased MD values throughout widespread WM areas predominately in the corpus callosum, bilateral internal capsule/corona radiata/posterior thalamic radiation/inferior fronto-occipital fasciculus and right inferior/superior longitudinal fasciculus. There was a slight discrepancy between the distribution of areas with decreased FA and LDH. The FA, MD and LDH values were significantly correlated with cognitive test results. According to a WM tract atlas, 10 major tracts were identified as tracts of interest in which three diffusion metrics simultaneously differed between groups, including bilateral anterior thalamic radiation, forceps minor, right corticospinal tract, bilateral inferior fronto-occipital fasciculus, left inferior and superior longitudinal fasciculus, and bilateral uncinate fasciculus. Receiver operating characteristic (ROC) analysis demonstrated the feasibility of using diffusion metrics along the forceps minor and left anterior thalamic radiation for separating two groups.Conclusion: The results suggest WM microstructural abnormalities contribute to cognitive impairments in SIVD patients. DTI parameters may be potential biomarkers for detecting VCIND from SIVD.

The neurobiological mechanism underlying adolescent borderline personality disorder (BPD) remains unclear. This study aimed to assess white matter (WM) microstructural abnormalities associated with emotional dysfunction and childhood trauma in adolescents with BPD. This study enrolled 53 adolescents aged 12-17 years with BPD and 39 healthy controls (HC). Radial diffusivity (RD) and axial diffusivity (AD) were generated using Tract-Based Spatial Statistics (TBSS) analysis of the diffusion tensor imaging (DTI) data. Correlation analysis was conducted to assess the relationship of the DTI parameters with non-suicidal self-injurious behavior (NSSI) and childhood trauma in adolescents with BPD. Adolescents with BPD had lower AD values in the splenium of the corpus callosum, left anterior corona radiata and left external capsule, but higher RD values in the genu of the corpus callosum, body of the corpus callosum, right anterior corona radiata, and right uncinate fasciculus as compared to the HC group (p < 0.05, 5000 permutations). Increased RD values in the body of corpus callosum and right uncinate fasciculus were positively correlated with the NSSI score (p < 0.05). Increased RD value in the right anterior corona radiata was positively correlated with childhood trauma (p < 0.05). This study identified alterations within the cortical-limbic system in adolescents with BPD, which was correlated with NSSI and childhood trauma. WM diffusivity parameters may serve as potential neuroimaging biomarkers in adolescents with BPD.