Lower Fractional Anisotropy Values Research Articles

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

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

Applicability of automated tractography during acute care stroke rehabilitation.

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

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

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

Diffusion Tensor Imaging for Interpreting Fractional Anisotropy and Mean Diffusivity in Normal-appearing White Matter of Patients with HIV-associated Neurocognitive Disorders: A Case-control Study

Introduction: {Human Immunodeficiency Virus (HIV)-associated Neurocognitive Disorder (HAND)} affects the everyday functioning of patients. It is usually difficult to diagnose HAND in the outpatient setting as detailed neuropsychological performance testing, such as the International HIV Dementia Scale (IHDS), is required. Neuroimaging techniques hold great promise in the early diagnosis and management of HAND, but there is a paucity of studies on the evaluation of HAND using Diffusion Tensor Imaging (DTI) in the Indian population. Aim: To investigate DTI and interpret Fractional Anisotropy (FA) and Mean Diffusivity (MD) values in the White Matter (WM) of patients with HAND and compare them with age and sex- matched controls. Materials and Methods: A case-control study was conducted at the Department of Radiodiagnosis, ABVIMS and Dr. RML Hospital, New Delhi, India, from January 2021 to May 2022. Thirty subjects (15 cases and 15 controls) were included. HIV-positive patients underwent the IHDS to assess cognitive impairment. Magnetic Resonance Imaging (MRI) examination was performed at three tesla using conventional sequences, and DTI was applied. Maps of FA and MD values were generated. Mean FA and MD values of normal-appearing white matter tracts between cases and controls were compared using a t-test. Spearman's correlation test was applied to assess the correlation between IHDS scores and DTI parameters. Results: The majority of cases in the study were in the age group of 31-40 years, and the mean age of cases was 41.27±11.16 years. The present study revealed significantly lower FA values compared to controls in bilateral Frontal WM, Parieto-occipital WM, genu of the Corpus Callosum (CC), right hippocampal WM, and right corona radiata. The mean MD of bilateral Frontal WM, Parieto-occipital WM, corona radiata, and Hippocampal WM was significantly increased in cases compared to healthy controls. A significant association was found between the IHDS score and FA values of the genu of the CC (rho= 0.7), right corona radiata (rho= 0.7), right Hippocampal WM (rho= 0.9), and MD of the left Parieto-occipital WM (rho= -0.6), and left hippocampal WM (rho= -0.5). Conclusion: Diffusion tensor MR imaging can detect abnormalities that are missed by routine MR imaging. DTI provides a valuable marker to monitor HIV-associated Central Nervous System (CNS) injury, which can lead to neurocognitive impairment.

Nerve abnormalities in lumbar disc herniation: A systematic review and meta-analysis of diffusion tensor imaging.

The purpose of this study was to examine the values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in diffusion tensor imaging (DTI) for diagnosing patients with nerve impairment due to lumbar disc herniation (LDH). A literature search of databases (PubMed, Web of Science, Cochrane Library and Embase) was systematically performed to identify articles published before September 2021 that were relevant to this study. FA and ADC estimates of compressed nerve roots due to LDH and healthy controls in the same segment were compared, with either fixed or random effects models selected according to I2 heterogeneity. Additionally, subgroup analysis, sensitivity analysis, potential publication bias analysis and meta-regression analysis were also performed. A total of 369 patients with LDH from 11 publications were included in this meta-analysis. The results showed significantly lower FA values (Weighted Mean Difference (WMD): -0.08, 95% confidence interval (CI): -0.09 to -0.07, P ≤ 0.001, I2 = 87.6%) and significantly higher ADC values (WMD: 0.25, 95% CI: 0.20 to 0.30, P ≤ 0.001, I2 = 71.4%) of the nerve on the compressed side due to LDH compared to the healthy side. Subgroup analysis indicated that different countries and magnetic field strengths may be associated with higher heterogeneity. Furthermore, meta-regression analysis further revealed that segment and field strength did not have a significant effect on the results, regardless of the FA or ADC values. Contrastingly, in FA, the year of publication, country, b value and directions showed an effect on the results. This meta-analysis showed a significant decrease in FA and a significant increase in ADC in patients with nerve damage due to LDH. The results favourably support the presence of nerve impairment in patients with LDH.

Lower fractional anisotropy without evidence for neuro-inflammation in patients with early-phase schizophrenia spectrum disorders

Various lines of research suggest immune dysregulation as a potential therapeutic target for negative and cognitive symptoms in schizophrenia spectrum disorders (SSD). Immune dysregulation would lead to higher extracellular free-water (EFW) in cerebral white matter (WM), which may partially underlie the frequently reported lower fractional anisotropy (FA) in SSD. We aim to investigate differences in EFW concentrations – a presumed proxy for neuro-inflammation – between early-phase SSD patients (n = 55) and healthy controls (HC; n = 37), and to explore immunological and cognitive correlates. To increase specificity for EFW, we study several complementary magnetic resonance imaging contrasts that are sensitive to EFW. FA, mean diffusivity (MD), magnetization transfer ratio (MTR), myelin water fraction (MWF) and quantitative T1 and T2 were calculated from diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT). For each measure, WM skeletons were constructed with tract-based spatial statistics. Multivariate SSD-HC comparisons with WM skeletons and their average values (i.e. global WM) were not statistically significant. In voxel-wise analyses, FA was significantly lower in SSD in the genu of the corpus callosum and in the left superior longitudinal fasciculus (p < 0.04). Global WM measures did not correlate with immunological markers (i.e. IL1-RA, IL-6, IL-8, IL-10 and CRP) or cognition in HC and SSD after corrections for multiple comparisons. We confirmed lower FA in early-phase SSD patients. However, nonFA measures did not provide additional evidence for immune dysregulation or for higher EFW as the primary mechanism underlying the reported lower FA values in SSD.

Local Alterations of Left Arcuate Fasciculus and Transcallosal White Matter Microstructure in Schizophrenia Patients with Medication-resistant Auditory Verbal Hallucinations: A Pilot Study

Auditory verbal hallucinations (AVH) in schizophrenia (SZ) have been associated with abnormalities of the left arcuate fasciculus and transcallosal white matter projections linking homologous language areas of both hemispheres. While most studies have used a whole-tract approach, here we focused on analyzing local alterations of the above-mentioned pathways in SZ patients suffering medication-resistant AVH. Fractional anisotropy (FA) was estimated along the left arcuate fasciculus and interhemispheric projections of the rostral and caudal corpus callosum. Then, potential associations between white matter tracts and SZ symptoms were explored by correlating local site-by-site FA values and AVH severity estimated via the Auditory Hallucinations Rating Scale (AHRS). Compared to a sample of healthy controls, SZ patients displayed lower FA values in the rostral portion of the left arcuate fasciculus, near the frontal operculum, and in the left and right lateral regions of the rostral portion of the transcallosal pathways. In contrast, SZ patients showed higher FA values than healthy controls in the medial portion of the latter transcallosal pathway and in the midsagittal section of the interhemispheric auditory pathway. Finally, significant correlations were found between local FA values in the left arcuate fasciculus and the severity of the AVH’s attentional salience. Contributing to the study of associations between local white matter alterations of language networks and SZ symptoms, our findings highlight local alterations of white matter integrity in these pathways linking language areas in SZ patients with AVH. We also hypothesize a link between the left arcuate fasciculus and the attentional capture of AVH.

Fractional anisotropy values of brain matter among healthy children: cohort study

INTRODUCTION: Diffusion-tensor magnetic resonance imaging (DT-MRI) is currently a well studied and applied in clinical practice technique. An important advantage of this technique is the measurement of fractional anisotropy (FA) values, which make it possible to quantify changes in brain matter. The authors are aware of publications on the study of FА values among children in small groups including only a part of ages. This work presents study of FA among large amount of examined children and notes values of FA for most of the significant structures of the brain in subjects from 4 months to 18 years of age.OBJECTIVE: Analysis of the FА values of the anatomical structures of the brain in children of different age groups who did not reveal changes in the brain matter during multiparametric MRI, in order to further study the processes of development and myelination of brain structures, as well as the use of these values in clinical practice as reference values in the analysis of pathology.MATERIALS AND METHODS: 153 patients aged from 4 months to 18 years were examined. MRI of brain was performed on the recommendation of the attending physician in accordance with clinical indications in case of suspected infection in the paranasal sinuses and neurological complaints, without focal symptoms. Distribution of examined children by age groups was: up to 1 year (infant age) — 6 children (3.9%); from 1 year to 3 years (early childhood) — 14 children (9.15%); from 3 to 7 years old (preschool age) — 39 children (25.5%); older than 7 years (school age and older) — 94 children (61.45%). Distribution of the examined by gender: male children — 82 (53.6%); female — 71 (46.4%). DT-MRI was applied to all patients with measurement of diffusion in 15 directions, and then FА values were measured in 21 areas of the white and gray matter of the brain. The regions of interest (ROI) were arranged in accordance with the zones of the ASPECTS and PC-ASPECTS scales adapted for the purposes of this study. Statistics: processing of the received data was carried out using application programs: Microsoft Excel, Statistica 10 with an assessment of the normality of the distribution of values and the use of parametric and nonparametric criteria.RESULTS: The highest mean numerical values of FA for all groups of children were found in the white matter along neural pathways: 0.66±0.04 for the internal capsule; 0.68±0.05 — in the white matter of the midbrain; 0.64±0.08 — at the level of the pons; 0.69±0.04 — in the cerebellar peduncles. The FA indices in the white matter of other anatomical regions are slightly lower: 0.50±0.08 — for white matter at the M4 level according to ASPECTS; 0.52±0.08 — in the occipital lobe at the level of the basal ganglia; 0.54±0.05 — in the temporal lobe. The lowest FA values appeared in the gray matter: 0.16±0.04 — in the caudate nucleus; 0.12±0.04 — in the gray matter at the M4 level according to ASPECTS. The most pronounced differences in FA in children of early childhood and school age appeared in the ROI located in the white matter of the cerebral cortex: in the area of M5 0.46±0.05 versus 0.54±0.05, respectively; in the area of M1 0.43±0.06 versus 0.51±0.06, respectively. At the same time, differences in FA in children of early childhood and school age in ROI located in the white matter at the level of stem structures are less pronounced: at the level of the pons 0.6±0.07 versus 0.64±0.07, respectively; at the level of the cerebellar peduncles 0.68±0.04 versus 0.69±0.04, respectively. These numerical indicators illustrate and additionally confirm the known ideas about the development and formation of neural pathways and about the processes of their myelination. They also reflect the known data on the structural and functional differences between the gray and white matter of the brain. A significant increase of the FА values in children older than 7 years was determined in comparison with groups of younger children in the white matter of the cortical structures of the brain. At the same time, there are no significant age-related differences of FА in the region of brainstem. It was also found that in preschoolers, compared with children from 1 to 3 years old, white matter FА increases in the region of the caudate nucleus and midbrain.CONCLUSION: The obtained normative values of FА can later be widely used in clinical practice as reference ones when performing DT-MRI and assessing neuroinfectious and other pathological changes in the brain matter in children. The revealed differences in age groups indicate an earlier development of brainstem structures, while the subcortical-cortical areas of the cerebral hemispheres develop and myelinate over a longer time.

Chronic anemia: The effects on the connectivity of white matter.

Chronic anemia is commonly observed in patients with hemoglobinopathies, mainly represented by disorders of altered hemoglobin (Hb) structure (sickle cell disease, SCD) and impaired Hb synthesis (e.g. thalassemia syndromes, non-SCD anemia). Both hemoglobinopathies have been associated with white matter (WM) alterations. Novel structural MRI research in our laboratory demonstrated that WM volume was diffusely lower in deep, watershed areas proportional to anemia severity. Furthermore, diffusion tensor imaging analysis has provided evidence that WM microstructure is disrupted proportionally to Hb level and oxygen saturation. SCD patients have been widely studied and demonstrate lower fractional anisotropy (FA) in the corticospinal tract and cerebellum across the internal capsule and corpus callosum. In the present study, we compared 19 SCD and 15 non-SCD anemia patients with a wide range of Hb values allowing the characterization of the effects of chronic anemia in isolation of sickle Hb. We performed a tensor analysis to quantify FA changes in WM connectivity in chronic anemic patients. We calculated the volumetric mean of FA along the pathway of tracks connecting two regions of interest defined by BrainSuite's BCI-DNI atlas. In general, we found lower FA values in anemic patients; indicating the loss of coherence in the main diffusion direction that potentially indicates WM injury. We saw a positive correlation between FA and hemoglobin in these same regions, suggesting that decreased WM microstructural integrity FA is highly driven by chronic hypoxia. The only connection that did not follow this pattern was the connectivity within the left middle-inferior temporal gyrus. Interestingly, more reductions in FA were observed in non-SCD patients (mainly along with intrahemispheric WM bundles and watershed areas) than the SCD patients (mainly interhemispheric).

Detection of post-stroke visual field loss by quantification of the retrogeniculate visual pathway

Visual field loss is associated with poor post-stroke functional outcomes. However, early detection of visual field loss is often challenging in patients with disabling stroke. This study explored the association between the microstructural integrity of the retrogeniculate pathway and visual field loss in disabling stroke patients undergoing inpatient rehabilitation. Thirty patients with stroke lesions involving the retrogeniculate visual pathway were included. The degree of visual field loss was determined by the visual field index and mean deviation using automated perimetry. The fractional anisotropy (FA) values were obtained for the lateral geniculate nucleus and optic radiation; the FA laterality indices, representing the degree of degeneration, were calculated. The FA values were compared between the affected and unaffected hemispheres. The patients were categorized into complete and incomplete hemianopia groups, and their FA values were compared. The relationship between the FA laterality index and the degree of visual field loss was assessed. FA values of the lateral geniculate nucleus and optic radiation were lower on the affected side than on the unaffected side (P < 0.001 and P < 0.001, respectively). The affected optic radiation in the complete hemianopia group showed a lower FA value than in the incomplete group (P = 0.006). The FA laterality index of the optic radiation was positively correlated with the degree of visual field loss (visual field index, ρ = 0.629; mean deviation, ρ = 0.568). The quantification of the retrogeniculate visual pathway may aid in detecting post-stroke visual field loss. The microstructural integrity of the optic radiation is associated with the severity of visual field loss.

P 9 A multi-modal in vivo staging approach to amyotrophic lateral sclerosis

Introduction: The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be classified as a four-stage propagation scheme. An in vivo transfer of these stages using diffusion tensor imaging (DTI) in specific tract systems has been established [1]. Since cognitive functions are closely linked to microstructural changes, an analogous classification into four cognitive stages, with high congruence to DTI stages, was demonstrated [2]. Alterations in oculomotor functions in ALS can be characterized by two stages in oculomotor parameters [3]. The objective of the current study is to show congruence of methods by combining neuroimaging, cognitive testing, and video-oculography (VOG) and to potentially improve in vivo staging classification. Methods: A total of 4 microstructural, 2 cognitive, and 9 oculomotor parameters were obtained from each of 193 patients with ALS. To this end, patients underwent VOG und cognitive testing using Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The regional fractional anisotropy (FA) of the tract systems involved in ALS [1] were studied using a tract-of-interest (TOI)-based approach. After z-standardization of all parameters, principal component analysis was performed. Hierarchical and k -means clustering of principal components was used to obtain an optimal cluster solution. Results: After reducing the considered parameters to four uncorrelated principal components, the patients were iteratively merged using pairwise distances. A division of patients into four clusters was used for further analysis. These clusters were different with regard to FA values during the progression of ALS-associated tract systems. Cluster 1 showed the highest FA values and thereby the best performances in executive VOG (e.g. performing correct anti-saccades) and cognitive tests, whereas ALS patients in cluster 4 showed lower FA values, lower ECAS scores and worse executive VOG performance. Patients in clusters 2 and 3 showed lower FA values compared to cluster 1 and higher FA values compared to cluster 4, while cognitive and executive VOG performance were altered only in cluster 2 compared to cluster 1. Conclusion: Cluster analysis of multimodal parameters, incorporating DTI, neuropsychologic testing, and VOG, showed high congruence of methodological approaches in ALS.

Lower fractional anisotropy of the corticothalamic tract and increased response time variability in adult patients with ADHD.

Background:Intraindividual intertrial variability has been suggested as an endophenotype of attention-deficit/hyperactivity disorder (ADHD). It is usually evaluated as response time variability (RTV) in reaction time tasks, and RTV has emerged as a robust and stable feature of ADHD. Among attempts to elucidate the neurobiological underpinnings of RTV, it has been suggested that alterations in white matter microstructure may explain RTV.Methods:We used diffusion tensor imaging (DTI) in a group of 53 adults with ADHD and 50 healthy controls. We obtained RTV parameters from a simple reaction-time task, in which participants were asked to respond to the appearance of white crosses on a screen using button presses.Results:We observed significant between-group differences for the ex-Gaussian parameter τ, indicating that the mean of extremely slow responses was greater for adults with ADHD than controls. Fractional anisotropy (FA) derived from DTI was significantly different between groups in 2 clusters of the corticothalamic tract. In the ADHD group, relatively decreased FA values were significantly associated with the parameter τ, such that lower FA values in the corticothalamic tract predicted greater τ as an index of RTV. We did not observe this association in healthy controls.Limitations:For comparison with previous studies, we used FA as a dependent variable of interest. However, although this metric is sensitive to white matter structural properties, there are ambiguities in its interpretation.Conclusion:Even in a simple reaction-time task, RTV proved again to be a stable feature of ADHD. It was associated with altered white matter structural properties of the corticothalamic tract in adults with ADHD.

Quantitative assessment of the intraorbital segment of the optic nerve in patients with thyroid orbitopathy using diffusion tensor imaging.

It is difficult to detect optic nerve changes in patients with thyroid-associated ophthalmopathy (TAO) before the development of optic neuropathy. To detect changes in the intraorbital segment of the optic nerve in patients with TAO using diffusion tensor imaging (DTI) and determine any correlations with disease severity. A total of 74 participants (17 normal, 22 mild, and 35 moderate-severe TAO) were organized to be given 3-T DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) for the orbital segments of their optic nerves. All underwent ophthalmological examinations for visual acuity, intraocular pressure, exophthalmos, and fundoscopy, and were assessed based on the Clinical Activity Score (CAS). Univariate analysis of variance and Pearson's correlation coefficients were carried out. Patients with moderate-to-severe TAO had significantly lower FA values and higher MD values (P < 0.05). FA values were negatively correlated with CAS but had no obvious correlations with the degree of exophthalmos. MD values had no obvious correlations with CAS or the degree of exophthalmos. DTI parameters of the intraorbital optic nerves were significantly altered in moderate-to-severe patients before onset of clinical optic nerve dysfunction and may, therefore, be used as an imaging biomarker for assessing the disease.

White-Matter Integrity and Working Memory: Links to Aging and Dopamine-Related Genes.

Working memory, a core function underlying many higher-level cognitive processes, requires cooperation of multiple brain regions. White matter refers to myelinated axons, which are critical to interregional brain communication. Past studies on the association between white-matter integrity and working memory have yielded mixed findings. Using voxelwise tract-based spatial statistics analysis, we investigated this relationship in a sample of 328 healthy adults from 25 to 80 years of age. Given the important role of dopamine (DA) in working-memory functioning and white matter, we also analyzed the effects of dopamine-related genes on them. There were associations between white-matter integrity and working memory in multiple tracts, indicating that working-memory functioning relies on global connections between different brain areas across the adult life span. Moreover, a mediation analysis suggested that white-matter integrity contributes to age-related differences in working memory. Finally, there was an effect of the COMT Val158Met polymorphism on white-matter integrity, such that Val/Val carriers had lower fractional anisotropy values than any Met carriers in the internal capsule, corona radiata, and posterior thalamic radiation. As this polymorphism has been associated with dopaminergic tone in the prefrontal cortex, this result provides evidence for a link between DA neurotransmission and white matter. Together, the results support a link between white-matter integrity and working memory, and provide evidence for its interplay with age- and DA-related genes.

Psychopathology and Integrity of the Superior Longitudinal Fasciculus in Deficit and Nondeficit Schizophrenia.

The superior longitudinal fasciculus (SLF) is a white matter bundle that connects the frontal areas with the parietal areas. As part of the visuospatial attentional network, it may be involved in the development of schizophrenia. Deficit syndrome (DS) is characterized by primary and enduring negative symptoms. The present study assessed SLF integrity in DS and nondeficit schizophrenia (NDS) patients and examined possible relationships between it and psychopathology. Twenty-six DS patients, 42 NDS patients, and 36 healthy controls (HC) underwent psychiatric evaluation and diffusion tensor imaging (DTI). After post-processing, fractional anisotropy (FA) values within the SLF were analyzed. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. The PANSS proxy for the deficit syndrome was used to diagnose DS. NDS patients had lower FA values than HC. DS patients had greater negative symptoms than NDS patients. After differentiating clinical groups and HC, we found no significant correlations between DTI measures and psychopathological dimensions. These results suggest that changes in SLF integrity are related to schizophrenia, and frontoparietal dysconnection plays a role in its etiopathogenesis. We confirmed that DS patients have greater negative psychopathology than NDS patients. These results are preliminary; further studies are needed.

Diffusion Tensor Imaging Technology to Quantitatively Assess Abnormal Changes in Patients With Thyroid-Associated Ophthalmopathy.

ObjectiveWe aim to investigate the feasibility of using diffusion tensor imaging (DTI) to evaluate changes in extraocular muscles (EOMs) and lacrimal gland (LG) in patients with thyroid-associated ophthalmopathy (TAO) and to evaluate disease severity.Materials and MethodsA total of 74 participants, including 17 healthy controls (HCs), 22 patients with mild TAO, and 35 patients with moderate-severe TAO, underwent 3-Tesla DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) of the EOMs and LG. Ophthalmological examinations, including visual acuity, exophthalmos, intraocular pressure, and fundoscopy, were performed. FA and MD values were compared among patients with different disease severity. Multiple linear regression was adopted to predict the impact of clinical variables on DTI parameters of orbital soft tissue.ResultsTAO patients’ EOMs and LG showed significantly lower FA values and higher MD compared to HCs’ (P < 0.05). Moderate-severe TAO patients’ EOMs and LG had dramatically lower FA and higher MD compared with HCs (P < 0.05). In addition, only the DTI parameters of the medial rectus were considerably different between mild and moderate-severe TAO patients (P = 0.017, P = 0.021). Multiple linear regression showed that disease severity had a significant impact on the DTI parameters of orbital soft tissue.ConclusionDTI is a useful tool for detecting microstructural changes in TAO patients’ orbital soft tissue. DTI findings, especially medial rectus DTI parameters, can help to indicate the disease severity in TAO patients.

Assessment of peripheral neuropathy in type 2 diabetes by diffusion tensor imaging

To evaluate the diagnostic accuracy of diffusion tensor imaging (DTI) in diabetic peripheral neuropathy (DPN) for patients with type 2 diabetes and detect the correlations with electrophysiology. A total of 27 patients with type 2 diabetes with DPN, 24 patients with type 2 diabetes without peripheral neuropathy (NDPN), as well as 32 healthy controls (HC) were enrolled in this study. Clinical examinations and neurophysiologic tests were used to determine the presence of DPN. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of peripheral nerves, including the tibial nerve (TN) and common peroneal nerve (CPN), were calculated. Receiver operating characteristic (ROC) analysis was performed for FA and ADC values. Pearson's correlation coefficient was used to assess the correlation between DTI and electrophysiology parameters in the patient group. The tibial and common peroneal nerve FAs were lowest (P=0.003, 0.001, respectively) and ADC was highest (P=0.004, 0.005, respectively) in the DPN group. The FA value of the axonal injury group was lower than that in the demyelination group (P=0.035, 0.01, respectively), while the ADC value was higher (P=0.02, 0.01, respectively). In the DPN group, FA value was positively correlated with motor conduction velocity (MCV) (tibial nerve: r=0.420, P=0.007; common peroneal nerve: r=0.581, P<0.001) and motor amplitude (MA) (tibial nerve: r=0.623, P<0.001; common peroneal nerve: r=0.513; P=0.001), while ADC values was negatively correlated with MCV (tibial nerve: r=-0.320, P=0.044; common peroneal nerve: r=-0.569; P<0.001), and MA (tibial nerve: r=-0.491, P=0.001; common peroneal nerve: r=-0.524; P=0.001). With a lower FA value and higher ADC value, DTI accurately discriminated DPN. The DTI multi-parameter quantitative analysis of peripheral nerves differentiated DPN axonal injury from the demyelinating lesion, and hence, could be applied in the diagnosis of DPN.

Cingulum bundle integrity in schizophrenia with auditory verbal hallucinations: A diffusion tensor imaging tractographic study.

Cingulum bundle (CB) is frequently implicated in schizophrenia; however, its role in specific symptoms of schizophrenia such as auditory verbal hallucinations (AVHs) is less explored. Few studies have reported association between reduced integrity of CB and severity of AVH. Using a symptom-based approach, this diffusion tensor imaging (DTI) tractographic study was aimed to assess and compare the integrity of CB in schizophrenia with AVH, schizophrenia without AVH and healthy controls. A total of 92 right-handed adult individuals (aged 18-50 yr) were recruited across three study groups. Those with Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of schizophrenia with AVH (group I; n=30) were compared to those with DSM-5 schizophrenia without lifetime AVH (group II; n=32) and healthy controls (group III; n=30; screened using Mini International Neuropsychiatric Interview version-7.0.0. and negative family history). Clinical assessments (groups I and II) included scale for assessment of positive symptoms, scale for assessment of negative symptoms, clinical global impression-schizophrenia and psychotic symptom rating scale. All participants underwent DTI, and quantitative tract-based measurements of fractional anisotropy (FA) were obtained for images using DTI studio version-3.0. All groups were comparable for age, gender, education and severity of illness. Group I had significantly lower FA values in the cingulate gyrus (CG) part of the left CB compared to groups II and III. No significant difference was found between groups II and III. The findings of this study suggest that the disruption in the left CB appears to be specific for AVH-positive schizophrenia. The finding is, however, preliminary subject to replication in future studies. Further investigations are needed to understand its relevance in the context of AVH-positive schizophrenia.

Neural correlates in the development of and recovery from dysphagia after supratentorial stroke: A prospective tractography study

BackgroundSwallowing impairment after stroke may be related to the state of the corticobulbar tract (CBT), which is the motor projection fiber responsible for deglutition, but evidence is still lacking regarding which parameter could relate to poststroke swallowing recovery as measured by videofluroscope findings. This prospective study evaluated diffusion tensor imaging (DTI) parameters among dysphagic stroke patients compared with those of nondysphagia stroke patients and age-matched healthy subjects and followed swallowing recovery in dysphagic patients as assessed with the Modified Barium Swallow Impairment Profile (MBSImP©). MethodsDiffusion tractography was performed in 69 subjects, consisting of 27 S patients with dysphagia, 18 healthy subjects and 24 S patients with no evidence of dysphagia. DTI was performed within 14 days of stroke onset. Follow-up DTI was performed in the dysphagic group at three months. The tract volume (TV) of the CBT and frontal operculum as determined by fractional anisotropy (FA) was compared among the 3 groups. Correlations of these parameters with initial dysphagia severity and swallowing parameters at baseline and 3 months postonset were assessed. ResultsAll stroke patients showed lower CBT TV on the affected and unaffected sides than those in the control group, even in those who showed no evidence of clinical dysphagia. The dysphagia group showed a greater reduction in CBT TV on the affected side (P < 0.001). Receiver operating characteristic analysis showed that cutoff values of 4.1 cm3 for TV and 0.24 for FA from the affected side could classify dysphagia with good accuracy (AUC = 0.77, 0.75, respectively) and specificity levels. FA values in the unaffected frontal operculum showed a significant correlation (rho = −0.40, P = 0.02) with swallowing outcome as observed by the total scores of MBSImP©. In addition, these values proved to be significant variables to predict swallowing outcome in multiple regression analysis (R2 = 0.6317, adjR2 = 0.5815, F = 12.58, p < 0.001, AIC = 203.65). ConclusionsEven when clinical dysphagia is not apparent, individuals with a supratentorial stroke may show reduced CBT parameters compared to healthy controls. Supratentorial stroke may manifest with dysphagia if a certain extent of CBT volume and white matter tract integrity is involved, with a greater degree of CBT injury in the affected sides determining poststroke dysphagia severity. In contrast, recovery was independent of the affected parameters, and an initial lower FA value in the unaffected frontal operculum was indicative of a poorer 3-month dysphagia outcome. DTI parameters obtained within two weeks of stroke onset may help classify those with dysphagia, predict recovery and help plain therapeutic strategies to maintain the adaptive role of the white matter tract, which is crucial in swallowing recovery.

White Matter Characteristics of Cognitive Impairment in Tap-Test Positive Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Tract-Based Spatial Study.

The present study was designed to systemically evaluate changes in the diffusion tensor imaging (DTI)-derived parameters of iNPH (idiopathic normal pressure hydrocephalus) patients with different responses to the tap test (TT), and to correlate cognitive impairment with white matter (WM) degeneration. This study included 22 iNPH patients and 14 healthy controls with structural magnetic resonance imaging (MRI) and DTI scanning. DTI was used to explore the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for all participants. DTI parameters were evaluated using an ROI (region of interest)-based and tract-based spatial statistics (TBSS) approach. Neuropsychological assessments and the idiopathic normal pressure hydrocephalus grading scoring scale (iNPHGS) were performed. Compared to the TT non-responders, the TT responders group had significantly lower FA values in the corpus callosum, cingulum cingulate gyrus, superior longitudinal fasciculus, and lower AD values in the right cingulum cingulate gyrus and the left posterior thalamic radiation. Besides, the MD values were significantly increased in the corpus callosum, left anterior corona radiata, and the RD values in the corpus callosum and cingulum cingulate gyrus. In addition, the cognitive improvement was negatively correlated with FA of the corpus callosum, cingulum cingulate gyrus, and MD values of the genu of corpus callosum. While, the cognitive improvement was positively related to the AD of the cingulum cingulate gyrus, superior longitudinal, and RD values of the corpus callosum, cingulum cingulate gyrus and uncinate fasciculus. The ROI specific WM lesions in iNPH patients are the underlying basis for cognitive impairment.