Analysis Of Fractional Anisotropy Research Articles

Fiber Microstructure Quantile (FMQ) Regression: A Novel Statistical Approach for Analyzing White Matter Bundles from Periphery to Core.

The structural connections of the brain's white matter are critical for brain function. Diffusion MRI tractography enables the in-vivo reconstruction of white matter fiber bundles and the study of their relationship to covariates of interest, such as neurobehavioral or clinical factors. In this work, we introduce Fiber Microstructure Quantile (FMQ) Regression, a new statistical approach for studying the association between white matter fiber bundles and scalar factors (e.g., cognitive scores). Our approach analyzes tissue microstructure measures based on quantile-specific bundle regions. These regions are defined according to the quantiles of fractional anisotropy (FA) from the periphery to the core of a population fiber bundle, which pools all individuals' bundles. To investigate how fiber bundle tissue microstructure relates to covariates of interest, we employ the statistical technique of quantile regression. Unlike ordinary regression, which only models a conditional mean, quantile regression models the conditional quantiles of a response variable. This enables the proposed analysis, where a quantile regression is fitted for each quantile-specific bundle region. To demonstrate FMQ Regression, we perform an illustrative study in a large healthy young adult tractography dataset derived from the Human Connectome Project-Young Adult (HCP-YA), focusing on particular bundles expected to relate to particular aspects of cognition and motor function. Importantly, our analysis considers sex-specific effects in brain-behavior associations. In comparison with a traditional method, Automated Fiber Quantification (AFQ), which enables FA analysis in regions defined along the trajectory of a bundle, our results suggest that FMQ Regression is much more powerful for detecting brain-behavior associations. Importantly, FMQ Regression finds significant brain-behavior associations in multiple bundles, including findings unique to males or to females. In both males and females, language performance is significantly associated with FA in the left arcuate fasciculus, with stronger associations in the bundle's periphery. In males only, memory performance is significantly associated with FA in the left uncinate fasciculus, particularly in intermediate regions of the bundle. In females only, motor performance is significantly associated with FA in the left and right corticospinal tracts, with a slightly lower relationship at the bundle periphery and a slightly higher relationship toward the bundle core. No significant relationships are found between executive function and cingulum bundle FA. Our study demonstrates that FMQ Regression is a powerful statistical approach that can provide insight into associations from bundle periphery to bundle core. Our results also identify several brain-behavior relationships unique to males or to females, highlighting the importance of considering sex differences in future research.

White Matter Organization and Cortical Thickness Differ Among Active Duty Service Members With Chronic Mild, Moderate, and Severe Traumatic Brain Injury.

Abstract This study compared findings from whole-brain diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) among 90 Active Duty Service Members with chronic mild traumatic brain injury (TBI; n = 52), chronic moderate-to-severe TBI (n = 17), and TBI-negative controls (n = 21). Data were collected on a Philips Ingenia 3T MRI with DTI in 32 directions. Results demonstrated that history of TBI was associated with differences in white matter microstructure, white matter volume, and cortical thickness in both mild TBI and moderate-to-severe TBI groups relative to controls. However, the presence, pattern, and distribution of these findings varied substantially depending on the injury severity. Spatially-defined forms of DTI fractional anisotropy (FA) analyses identified altered white matter organization within the chronic moderate-to-severe TBI group, but they did not provide clear evidence of abnormalities within the chronic mild TBI group. In contrast, DTI FA "pothole" analyses identified widely distributed areas of decreased FA throughout the white matter in both the chronic mild TBI and chronic moderate-to-severe TBI groups. Additionally, decreased white matter volume was found in several brain regions for the chronic moderate-to-severe TBI group compared with the other groups. Greater number of DTI FA potholes and reduced cortical thickness were also related to greater severity of self-reported symptoms. In sum, this study expands upon a growing body of literature using advanced imaging techniques to identify potential effects of brain injury in military Service Members. These findings may differ from work in other TBI populations due to varying mechanisms and frequency of injury, as well as a potentially higher level of functioning in the current sample related to the ability to maintain continued Active Duty status after injury. In conclusion, this study provides DTI and volumetric MRI findings across the spectrum of TBI severity. These results provide support for the use of DTI and volumetric MRI to identify differences in white matter microstructure and volume related to TBI. In particular, DTI FA pothole analysis may provide greater sensitivity for detecting subtle forms of white matter injury than conventional DTI FA analyses.

Sex-related differences in upper limb motor function in healthy subjects and multiple sclerosis patients: a multiparametric MRI study.

We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS.

Alterations in Human Hippocampus Subregions across the Lifespan: Reflections on White Matter Structure and Functional Connectivity.

During growth and aging, the role of the hippocampus in memory depends on its interactions with related brain regions. Particularly, two subregions, anterior hippocampus (aHipp) and posterior hippocampus (pHipp), play different and critical roles in memory processing. However, age-related changes of hippocampus subregions on structure and function are still unclear. Here, we investigated age-related structural and functional characteristics of 106 participants (7-85 years old) in resting state based on fractional anisotropy (FA) and functional connectivity (FC) in aHipp and pHipp in the lifespan. The correlation between FA and FC was also explored to identify the coupling. Furthermore, the Wechsler Abbreviated Scale of Intelligence (WASI) was used to explore the relationship between cognitive ability and hippocampal changes. Results showed that there was functional separation and integration in aHipp and pHipp, and the number of functional connections in pHipp was more than that in aHipp across the lifespan. The age-related FC changes showed four different trends (U-shaped/inverted U-shaped/linear upward/linear downward). And around the age of 40 was a critical period for transformation. Then, FA analyses indicated that all effects of age on the hippocampal structures were nonlinear, and the white matter integrity of pHipp was higher than that of aHipp. In the functional-structural coupling, we found that the age-related FA of the right aHipp (aHipp.R) was negatively related to the FC. Finally, through the WASI, we found that the age-related FA of the left aHipp (aHipp.L) was positively correlated with verbal IQ (VERB) and vocabulary comprehension (VOCAB.T), the FA of aHipp.R was only positively correlated with VERB, and the FA of the left pHipp (pHipp.L) was only positively correlated with VOCAB.T. These FC and FA results supported that age-related normal memory changes were closely related to the hippocampus subregions. We also provided empirical evidence that memory ability was altered with the hippocampus, and its efficiency tended to decline after age 40.

Obsessive compulsive symptom dimensions are linked to altered white-matter microstructure in a community sample of youth

Obsessive-compulsive symptoms (OCS) are common in school-aged children and predict the development of obsessive compulsive disorder (OCD). White-matter abnormalities have been described in OCD, but the white matter correlates of OCS in the developing brain are unclear. Some correlates of OCS (or a diagnosis of OCD) may reflect correlates of a transdiagnostic or even general psychopathology factor. We examined these questions in a large sample of typically developing youth (N = 1208), using a hierarchical analysis of fixel-based white matter measures in relation to OCS and general psychopathology. General psychopathology was associated with abnormalities in the posterior corpus callosum and forceps major in an age-dependent manner, suggesting altered maturation (specifically, hypermaturation in younger subjects). A unidimensional measure of OCS did not associate with any white-matter abnormalities, but analysis of separate OCS dimensions (derived from factor analysis within this sample) revealed the ‘Bad Thoughts’ dimension to associate with white-matter abnormalities in dorsal parietal white-matter and descending corticospinal tracts, and the ‘Symmetry’ dimension to associate with abnormalities in the anterior corpus callosum. Repetition/checking and Symmetry OCS were additionally associated with posterior abnormalities overlapping with the correlates of general psychopathology. Contamination symptoms had no white-matter correlates. Secondary analysis of fractional anisotropy (FA) revealed distinct white-matter abnormalities, suggesting that fixel-based and FA analyses identify distinct features of white matter relevant to psychopathology. These findings suggest that OCS dimensions correlate with dissociable abnormalities in white matter, implicating separable networks. Future studies should examine these white-matter signatures in a longitudinal framework.

Association between gray/white matter contrast and white matter microstructural alterations in medication-naïve obsessive–compulsive disorder

Intracortical myelin is involved in speeding and synchronizing neural activity of the cerebral cortex and has been found to be disrupted in various psychiatric disorders. However, its role in obsessive–compulsive disorder (OCD) has remained unknown. In this study, we investigated the alterations in intracortical myelin and their association with white matter (WM) microstructural abnormalities in OCD. T1-weighted and diffusion-weighted brain images were obtained for 51 medication-naïve patients with OCD and 26 healthy controls (HCs). The grey/white matter contrast (GWC) was calculated from T1-weighted signal intensities to characterize the intracortical myelin profile in OCD. Diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were extracted from diffusion-weighted images to examine the WM microstructure in OCD. Compared with HCs, patients with OCD showed increased GWC in the bilateral orbitofrontal, cuneus, lingual and fusiform gyrus, left anterior cingulate, left superior parietal, right inferior parietal, and right middle frontal cortices, suggesting reduced intracortical myelin. Patients with OCD also showed decreased FA in several WM regions, with a topology corresponding to the GWC alterations. In both groups, the mean GWC of the significant clusters in between-group GWC analysis was correlated negatively with the mean FA of the significant clusters in between-group FA analysis. In patients with OCD, the FA of a cluster in the right cerebellum correlated negatively with the Yale-Brown obsessive–compulsive scale scores. Our results suggest that abnormal intracortical and WM myelination could be the microstructural basis for the brain connectivity alterations and disrupted inhibitory control in OCD.

White matter disconnection and decreased functional connectivity between orbitofrontal cortex and the contralateral temporo-occipital cortex in adults with obsessive compulsive disorder

IntroductionObsessive compulsive disorder (OCD) affects 2-3% of the general population. The neurobiology of OCD has been linked to dysfunction of cortico-striatal circuits connecting the orbitofrontal (OFC) to the striatum. Recently, this loop has become an approved target for non-invasive neuromodulatory treatment of OCD.ObjectivesTo explore structural and functional connectivity of the OFC in OCD subjects and healthy controls.Methods14 OCD patients and 12 age/sex-matched controls underwent magnetic resonance imaging (MRI) (3T-Philips scanner) for diffusion tensor imaging (DTI) and resting state functional connectivity (rsFC). DTI images were brain extracted and corrected for movement and eddy currents. A diffusion tensor model was fitted to each voxel and used to generate Fractional Anisotropy (FA) maps. Voxel-wise statistical analysis of FA was performed using Tract-Based Spatial Statistics. RsFC images were preprocessed and seed-based correlation (SBC) analysis was performed using Data Processing Assistant for Resting-State fMRI.ResultsWe found decreased values of FA in the body of the Corpus Callosum bilaterally (MNI_coordinates: x= 16, y= -16, z= 33 and x= -19, y= -16, z= 42) and left superior longitudinal fasciculus in OCD patients (fig 1, left), as well as decreased rsFC of the right superior orbitofrontal seed with the left inferior frontal gyrus and left middle occipital gyrus (fig 2, right).ConclusionsUsing an exploratory multimodal approach we found evidence of abnormal structural and functional long-range connectivity of the OFC in OCD. If confirmed in a larger sample these connectivity abnormalities could be explored as potential predictors of response to OFC-targeted non-invasive neuromodulatory interventions.DisclosureNo significant relationships.

Comparison of Canine and Feline Meningiomas Using the Apparent Diffusion Coefficient and Fractional Anisotropy.

Meningiomas are the most common intracranial tumor in dogs and cats, and their surgical resection is often performed because they are present on the brain surface. Typical meningiomas show comparatively characteristic magnetic resonance imaging findings that lead to clinical diagnosis; however, it is necessary to capture not only macroscopic changes but also microstructural changes to devise a strategy for surgical resection and/or quality of removal. To visualize such microstructural changes, diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have been used in human medicine. The aim of this retrospective study was to investigate the different characteristics of the apparent diffusion coefficient (ADC) from DWI and fractional anisotropy (FA) from DTI of meningioma between dogs and cats. Statistical analyses were performed to compare ADC and FA values between the intratumoral or peritumoral regions and normal-appearing white matter (NAWM) among 13 dogs (13 lesions, but 12 each in ADC and FA analysis) and six cats (seven lesions). The NAWM of cats had a significantly lower ADC and higher FA compared to dogs. Therefore, for a comparison between dogs and cats, we used ADC and FA ratios that were calculated by dividing the subject (intra- or peritumoral) ADC and FA values by those of NAWM on the contralateral side. Regarding the intratumoral region, feline meningiomas showed a significantly lower ADC ratio and higher FA ratio than canine meningiomas. This study suggested that ADC and FA may be able to distinguish a meningioma that is solid and easy to detach, like as typical feline meningiomas.

Uncinate fasciculus and its cortical terminals in aphasia after subcortical stroke: A multi-modal MRI study

Aphasia, one of the most common cognitive impairments after stroke, is commonly considered to be a cortical deficit. However, many studies have reported cases of post subcortical stroke aphasia (PSSA). The pathology and recovery mechanism of PSSA remain unclear. This study aimed to investigate PSSA mechanism through a multimodal magnetic resonance imaging (MRI) approach and a two-session study design (baseline and one month after treatment). Thirty-six PSSA patients and twenty-four matched healthy controls (HC) were included. All patients had subcortical infarctions involving left subcortical white matter for 1 to 6 months. The patients underwent MRI scan and Western Aphasia Battery (WAB) examination before and after one month’s comprehensive treatment. Region-wise lesion-symptom mapping (RLSM), tractography, fractional anisotropy (FA), and amplitude of low-frequency fluctuations (ALFF) analysis were conducted. After MRI preprocessing and exclusion, FA analysis included 35 patients pre-treatment and 16 patients post-treatment. ALFF analysis included 30 patients pre-treatment and 14 patients post-treatment. We found: 1) the amount of damage in the left uncinate fasciculus (UF) was associated with WAB aphasia quotient (AQ); 2) the left UF FA and left temporal pole (TP) ALFF were decreased and positively correlated with WAB-AQ, spontaneous speech, and naming in PSSA patients; and 3) PSSA patients showed increased left TP ALFF when their language ability recovered after treatment. The left TP ALFF change was positively correlated with AQ change. Our results demonstrate the importance of left UF and left TP (one of the cortical terminals of the left UF) in PSSA pathology and recovery. These results may further provide support for the disconnection theory in the mechanism of PSSA.

Association of Heavy Drinking With Deviant Fiber Tract Development in Frontal Brain Systems in Adolescents

Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood. To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents. This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking. Self-reported alcohol consumption in the past year summarized by categorical drinking levels. Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope. Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = -2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = -0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence. This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.

Is treatment-resistant schizophrenia associated with distinct neurobiological callosal connectivity abnormalities?

Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE)<0.05. We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.

Language hemispheric dominance analyzed with magnetic resonance DTI: correlation with the Wada test.

Language lateralization is a major concern in some patients with pharmacoresistant epilepsy who will face surgery; in these patients, hemispheric dominance testing is essential to avoid further complications. The Wada test is considered the gold standard examination for language localization, but is invasive and requires many human and material resources. Functional MRI and tractography with diffusion tensor imaging (DTI) have demonstrated that they could be useful for locating language in epilepsy surgery, but there is no evidence of the correlation between the Wada test and DTI MRI in language dominance. The authors performed a retrospective review of patients who underwent a Wada test before epilepsy surgery at their institution from 2012 to 2017. The authors retrospectively analyzed fractional anisotropy (FA), number and length of fibers, and volume of the arcuate fasciculus and uncinate fasciculus, comparing dominant and nondominant hemispheres. Ten patients with temporal lobe epilepsy were reviewed. Statistical analysis showed that the mean FA of the arcuate fasciculus in the dominant hemisphere was higher than in the nondominant hemisphere (0.369 vs 0.329, p = 0.049). Also, the number of fibers in the arcuate fasciculus was greater in the dominant hemisphere (881.5 vs 305.4, p = 0.003). However, no differences were found in the FA of the uncinate fasciculus or number of fibers between hemispheres. The length of fibers of the uncinate fasciculus was longer in the dominant side (74.4 vs 50.1 mm, p = 0.05). Volume in both bundles was more prominent in the dominant hemisphere (12.12 vs 6.48 cm3, p = 0.004, in the arcuate fasciculus, and 8.41 vs 4.16 cm3, p = 0.018, in the uncinate fasciculus). Finally, these parameters were compared in patients in whom the seizure focus was situated in the dominant hemisphere: FA (0.37 vs 0.30, p = 0.05), number of fibers (114.4 vs 315.6, p = 0.014), and volume (12.58 vs 5.88 cm3, p = 0.035) in the arcuate fasciculus were found to be statistically significantly higher in the dominant hemispheres. Linear discriminant analysis of FA, number of fibers, and volume of the arcuate fasciculus showed a correct discrimination in 80% of patients (p = 0.024). The analysis of the arcuate fasciculus and other tract bundles by DTI could be a useful tool for language location testing in the preoperative study of patients with refractory epilepsy.

M160. INVESTIGATING STRUCTURAL CONNECTIVITY CORRELATES OF VERBAL MEMORY DEFICITS AMONG FIRST-EPISODE PSYCHOSIS PATIENTS

BackgroundVerbal memory is one of the most affected cognitive domains in patients with schizophrenia and related psychoses. Several studies have found associations between cognitive abilities and white matter fractional anisotropy (FA) in schizophrenia; however, only a few tractography studies have investigated FA relative to verbal memory in patients with a first episode of psychosis (FEP) compared with healthy controls (HC). Although white matter tractography differences have been well established between chronic patients and HC, the direction of findings from FEP studies has been inconsistent. Thus, the present study aims to examine whole-brain white matter differences and its association with verbal memory in individuals with a FEP relative to HC using tractography.MethodsDiffusion-weighted images were acquired on a 1.5T scanner for patients (n=65) and controls (n=54) at baseline. The Wechsler Memory Scale was used as a measure of verbal memory. Pre-processing was performed on a subject-by-subject basis using MRtrix. Diffusion tractography was generated using a probabilistic anatomically-constrained tractography algorithm, which constrains the reconstruction to specific biological priors. Furthermore, the spherical-deconvolution informed filtering of tractograms (SIFT) tool will be used to ensure the tractogram is biologically meaningful. This results in subject-specific connectomes defining the mean FA between two regions of interest that were defined using the Desikan- Killiany atlas. A linear model was used to test for main effect of group and main effect of verbal memory on white matter tract FA, covarying for age and sex. For both sets of analyses, results were corrected for multiple comparisons using false discovery rate (FDR).ResultsA significant main effect of group on whole-brain average FA was observed, with patients displaying lower average FA compared to healthy controls (Patients=0.291, controls=0.300, p<0.05). Whole-brain white matter tract FA analysis revealed that there are widespread differences between controls and individuals with a FEP. Group most strongly predicted white matter tract FA differences between left caudal anterior cingulate and left lateral orbitofrontal (patients mean FA=0.302, controls mean FA=0.342), left hippocampus and right isthmus cingulate (patient mean FA= 0.217 controls mean FA= 0.318), and finally left lingual and left rostral anterior cingulate (patients mean FA=0.162, controls mean FA= 0.249. However, none survived correction for multiple comparisons. Further, there was no significant association between verbal memory and white matter tract FA in FEP or HC.DiscussionFindings from this study suggest there are some significant differences in whole-brain average FA between individuals experiencing a FEP and healthy controls. However, when analyzing whole-brain tract FA, none of the connections survived corrections for multiple comparisons. These findings might be limited by the scanner resolution included in this study, which may not capture more subtle differences. Nonetheless, these results are consistent with a cross-sectional study comparing healthy individuals to chronic and first-episode patients suggesting that modest differences are present early in the disease and increase as the disease progresses. We suggest that future studies analyze white matter tract using a longitudinal design to identify disease progression.

DIFFUSION TENSOR MAGNETIC RESONANCE IMAGING IN EARLY DIAGNOSIS OF STRUCTURAL CHANGES IN BRAIN WHITE MATTER IN SMALL VESSEL DISEASE ASSOCIATED WITH ARTERIAL HYPERTENSION AND IONIZING RADIATION.

to determine the early signs of structural changes in brain white matter in small vessel disease associated with arterial hypertension and exposure to ionizing radiation using DTI-MRI. 45 patients (mean age (57.56 ± 6.34) years) with small vessel disease (SVD) associatedwith arterial hypertension (AH) were examined: group I - 20 patients, participants of liquidation of the accident atthe Chornobyl nuclear power plant (Chornobyl clean-up workers); group II - 25 patients not exposed to ionizingradiation. MRI was performed on an Ingenia 3T tomograph («Philips»). The fractional anisotropy (FA) was determined in the main associative and commissural pathways, periventricular prefrontal areas (fasciculus fronto-occipitalis superior / anterior - f. FO ant., corona radiata anterior - CR ant.) and semioval centers (SC). No signs of cerebral cortex or brain white matter (WM) atrophy, intracerebral microhemorrhages, and widespread areas of leukoaraiosis consolidation were observed in the examined patients. In the Chornobyl clean-up workers a larger number of foci of subcortical leukoaraiosis was visualized (80 %) on MRI images including multiple -8 (40 %), > 0.5 cm - 10 (50 %), with signs of consolidation - 5 (25 %). The results of the FA analysis in semiovalcenters showed its significant decrease in the patients of groups I and II (p < 0,007), regardless of the presence orabsence of visual signs of subcortical leukoaraiosis (ScLA) (III gr.: 253-317, p < 0.00001; IV gr.: 287- 375,p < 0.001). FA indicators in f. FO ant. and CR ant. in the patients of groups I and II differed insignificantly but weresubstantially lower than controls (p < 0.05). FA was significantly lower, compared to reference levels, in visuallyunchanged f. FO ant. (0.389-0.425; p = 0.015) and CR ant. (0.335-0.403; p = 0.05). In patients with AH-associated SVD of middle age, regardless of the effects of ionizing radiation, no significant changes in FA in the mainWM associative and commissural pathways were found (p > 0.05). DTI-MRI allows to detect early signs of structural changes in the white matter of the brain - a significant decrease in fractional anisotropy indicators in visually unchanged periventricular and subcortical areas. Themain associative and commissural pathways of the brain remain intact in the absence of widespread consolidatedfoci of leukoaraiosis and lacunar infarctions. The negative impact of ionizing radiation on the course of SVD associated with arterial hypertension is manifested by more active processes of WM disorganization: the prevalence andtendency to the consolidation of periventricular and subcortical leukoaraiosis foci, a significant FA decrease in semioval centers.

White Matter by Diffusion MRI Following Methylphenidate Treatment: A Randomized Control Trial in Males with Attention-Deficit/Hyperactivity Disorder.

BackgroundMethylphenidate (MPH) is highly effective in treating attention-deficit/hyperactivity disorder (ADHD). However, not much is known about its effect on the development of human brain white matter (WM).PurposeTo determine whether MPH modulates WM microstructure in an age-dependent fashion in a randomized double-blind placebo-controlled trial (Effects of Psychotropic Medication on Brain Development-Methylphenidate, or ePOD-MPH) among ADHD referral centers between October 13, 2011, and June 15, 2015, by using diffusion-tensor imaging (DTI).Materials and MethodsIn this prospective study (NTR3103 and NL34509.000.10), 50 stimulant treatment-naive boys and 49 young adult men diagnosed with ADHD (all types) according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria were randomized to undergo treatment with MPH or placebo for 16 weeks. Before and 1 week after treatment cessation, study participants underwent MRI, including DTI. The outcome measure was change in fractional anisotropy (FA), which was assessed in three regions of interest (ROIs), as well as in a voxel-based analysis in brain WM. Data were analyzed by using intention-to-treat linear mixed models for ROI analysis and a permutation-based method for voxel-based analysis with family-wise error correction.ResultsFifty boys (n = 25 MPH group, n = 25 placebo group; age range, 10-12 years) and 48 men (n = 24 MPH group, n = 24 placebo group; age range, 23-40 years) were included. ROI analysis of FA yielded no main effect of time in any of the conditions. However, voxel-based analysis revealed significant (P < .05) time-by-medication-by-age interaction effects in several association tracts of the left hemisphere, as well as in the lateral aspect of the truncus of the corpus callosum, due to greater increase in FA (standardized effect size, 5.25) in MPH-treated boys. Similar changes were not present in boys receiving a placebo, nor in adult men.ConclusionFour months of treatment with methylphenidate affects specific tracts in brain white matter in boys with attention-deficit/hyperactivity disorder. These effects seem to be age dependent, because they were not observed in adults treated with methylphenidate.© RSNA, 2019Online supplemental material is available for this article.

Altered structural brain network resulting from white matter injury in obstructive sleep apnea.

To assess, using fractional anisotropy (FA) analysis, alterations of brain network connectivity in adults with obstructive sleep apnea (OSA). Abnormal networks could mediate clinical functional deficits and reflect brain tissue injury. Structural brain networks were constructed using diffusion tensor imaging (DTI) from 165 healthy (age 57.99 ± 6.02 years, male 27.9%) and 135 OSA participants (age 59.01 ± 5.91 years, male 28.9%) and global network properties (strength, global efficiency, and local efficiency) and regional efficiency were compared between groups. We examined MRI biomarkers of brain tissue injury using FA analysis and its effect on the network properties. Differences between groups of interest were noted in global network properties (p-value < 0.05, corrected), and regional efficiency (p-value < 0.05, corrected) in the left middle cingulate and paracingulate gyri, right posterior cingulate gyrus, and amygdala. In FA analysis, OSA participants showed lower FA values in white matter (WM) of the right transverse temporal, anterior cingulate and paracingulate gyri, and left postcentral, middle frontal and medial frontal gyri, and the putamen. After culling fiber tracts through WM which showed significant differences in FA, we observed no group difference in network properties. Changes in WM integrity and structural connectivity are present in OSA participants. We found that the integrity of WM affected brain network properties. Brain network analysis may improve understanding of neurocognitive deficits in OSA, enable longitudinal tracking, and provides explanations for specific symptoms and recovery kinetics.

Longitudinal Analysis of Corpus Callosum Diffusion Tensor Imaging Metrics and Its Association with Neurological Outcome

Traumatic axonal injury (TAI) is the main cause of cognitive and psychological disfunction after a traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique for indirect assessment of white matter (WM) integrity after a TBI. Scattered WM alterations and its relationship with patient severity have been discovered in normal appearing conventional magnetic resonance imaging (MRI) studies based on DTI sequences. However, there is a lack of large sample studies on the longitudinal changes of DTI metrics to be used to determine the temporal profile after head injury and its association with patient outcome. We performed a prospective observational study in 118 moderate-to-severe TBI patients. The study included clinical outcome assessment based on the Glasgow Outcome Scale Extended (GOSE) and serial DTI studies in the early subacute setting (< 60 days) and 6 and 12 months after injury. Fractional anisotropy (FA) and axial and radial diffusivities (AD and RD, respectively) were measured in the three portions of corpus callosum (genu, body, splenium) at each time-point and compared with normalized values from an age-matched control group. Longitudinal FA analysis and its correlation with patient improvement also was done by non-parametric testing and ordinal regression analysis. Our main results indicated that between all the time-points, dynamic changes in DTI metrics in all three portions of corpus callosum were detected, but TBI patients continued to show significantly lower FA and AD values and higher RD values compared with controls. We also have discovered differences in the change of DTI metrics among different time-points in patient subgroups according with their outcome improvement. In conclusion, even without normalization of DTI metrics in the long-term, knowledge of the temporal profile of change in DTI metrics can provide important information about patients' clinical recovery after TBI.

Widespread white matter connectivity abnormalities in narcolepsy type 1: A diffusion tensor imaging study.

Narcolepsy type 1 is caused by a selective loss of hypothalamic hypocretin-producing neurons, resulting in severely disturbed sleep-wake control and cataplexy. Hypocretin-producing neurons project widely throughout the brain, influencing different neural networks. We assessed the extent of microstructural white matter organization and brain-wide structural connectivity abnormalities in a homogeneous group of twelve drug-free patients with narcolepsy type 1 and eleven matched healthy controls using diffusion tensor imaging with multimodal analysis techniques. First, tract-based spatial statistics (TBSS) was carried out using fractional anisotropy (FA) and mean, axial and radial diffusivity (MD, AD, RD). Second, quantitative analyses of mean FA, MD, AD and RD were conducted in predefined regions-of-interest, including sleep-wake regulation-related, limbic and reward system areas. Third, we performed hypothalamus-seeded tractography towards the thalamus, amygdala and midbrain. TBSS analyses yielded brain-wide significantly lower FA and higher RD in patients. Localized significantly lower FA and higher RD in the left ventral diencephalon and lower AD in the midbrain, were seen in patients. Lower FA was also found in patients in left hypothalamic fibers connecting with the midbrain. No significant MD and AD differences nor a correlation with disease duration were found. The brain-wide, localized ventral diencephalon (comprising the hypothalamus and different sleep- and motor-related nuclei) and hypothalamic connectivity differences clearly show a heretofore underestimated direct and/or indirect effect of hypocretin deficiency on microstructural white matter composition, presumably resulting from a combination of lower axonal density, lower myelination and/or greater axon diameter.

Diffusion tensor imaging parameters in differentiation recurrent breast cancer from post-operative changes in patients with breast-conserving surgery

Aim of the workTo investigate mean diffusivity (MD) and fractional anisotropy (FA) measured by diffusion tensor imaging (DTI) as complementary tools to differentiate recurrent breast cancer from post-operative changes in patients with breast-conserving surgery (BCS). Patients and MethodsProspective study was conducted upon 30 patients with BCS that underwent DTI and dynamic contrast MR imaging. DTI was performed using an axial two-dimensional spin-echo echo-planar imaging sequence. The MD and FA of the lesions were calculated by 2 observers. A single pixel seed isotropic region of interest was placed in the solid part of the tumor on the axial color FA map guided by an enhanced part of the tumor. The final diagnosis was done by biopsy for all patients. ResultsThe pathological examination proved to be recurrent breast cancer (n = 13) and post-operative changes (n = 17). Recurrent breast cancer had significantly lower MD (P = 0.001, 0.001) and higher FA (P = 0.003, 0.02) than in post-operative changes for both observers respectively. At ROC curve analysis of MD, the AUC was 0.86 and 0.85 by both observers. The threshed MD was (0.86, 0.85 × 10−3 mm2/s) used for differentiation between entities revealed sensitivity (76.9%, 92.3%), specificity (82.4%, 64.7%) and accuracy (80%, 76.7%) of both observers respectively. At ROC curve analysis of FA, the AUC was 0.82 and 0.75 by both observers. The threshold FA (0.82, 0.75) was used for differentiation between entities revealed sensitivity (92.3%, 76.9%), specificity (70.6%, 70.6%) and accuracy of (80.0%, 73.3%) of both observers respectively. There was a strong positive correlation of MD (r = 0.86) and FA (r = 0.73) of both observers. Combined analysis of FA and MD used for differentiation between entities had AUC (0.90, 0.88) revealed sensitivity (92.3%, 92.3%), specificity (82.4%, 70.6%) and accuracy of (86.7%, 80.0%) for both observers respectively. ConclusionsCombined analysis of MD and FA of DTI may play an important role as a non-invasive method for differentiation recurrent breast cancer from post-operative changes in patients with BCS.

Differences in white matter connectivity between treatment-resistant and treatment-responsive subtypes of schizophrenia

Schizophrenia is a heterogeneous disorder exhibiting variable responsiveness to treatment between individuals. Previous work demonstrated that white matter abnormalities may relate to antipsychotic response but no study to date has examined differences between first-line treatment responders (FLR) and clozapine-eligible individuals receiving first-line antipsychotics. The current study aimed to establish whether differences in white matter structure exist between these two cohorts. Diffusion-weighted images were acquired for 15 clozapine-eligible and 10 FLR participants. Measures of fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) were obtained and between-group t-tests interrogating differences in FA were conducted. To investigate the neural basis of a decrease in FA, the significant cluster from FA analysis was masked and used to obtain mean RD and AD measures for that region. Those who were clozapine-eligible had significantly lower FA in the body of the corpus callosum (p < 0.05), associated with a significant increase in mean RD compared with FLR (p < 0.001). No difference in mean AD was observed for this region. These data reveal differences in diffusion measures between FLR and those eligible for clozapine and suggest that lower FA and greater RD in the corpus callosum could exist as a biomarker of treatment resistance in people with schizophrenia.