Feasibility of detecting atrophy relevant for disability and cognition in multiple sclerosis using 3D-FLAIR.

BACKGROUND AND OBJECTIVES: Disability and cognitive impairment are known to be related to brain atrophy in multiple sclerosis (MS), but 3D-T1 imaging required for brain volumetrics is often unavailable in clinical protocols, unlike 3D-FLAIR. Here our aim was to investigate whether brain volumes derived from 3D-FLAIR images result in similar associations with disability and cognition in MS as do those derived from 3D-T1 images. METHODS: 3T-MRI scans of 329 MS patients and 76 healthy controls were included in this cross-sectional study. Brain volumes were derived using FreeSurfer on 3D-T1 and compared with brain volumes derived with SynthSeg and SAMSEG on 3D-FLAIR. Relative agreement was evaluated by calculating the intraclass correlation coefficient (ICC) of the 3D-T1 and 3D-FLAIR volumes. Consistency of relations with disability and average cognition was assessed using linear regression, while correcting for age and sex. The findings were corroborated in an independent validation cohort of 125 MS patients. RESULTS: The ICC between volume measured with FreeSurfer and those measured on 3D-FLAIR for brain, ventricle, cortex, total deep gray matter and thalamus was above 0.74 for SAMSEG and above 0.91 for SynthSeg. Worse disability and lower average cognition were similarly associated with brain (adj. R2 = 0.24-0.27, p < 0.01; adj. R2 = 0.26-0.29, p < 0.001) ventricle (adj. R2 = 0.27-0.28, p < 0.001; adj. R2 = 0.19-0.20, p < 0.001) and deep gray matter volumes (adj. R2 = 0.24-0.28, p < 0.001; adj. R2 = 0.27-0.28, p < 0.001) determined with all methods, except for cortical volumes derived from 3D-FLAIR. DISCUSSION: In this cross-sectional study, brain volumes derived from 3D-FLAIR and 3D-T1 show similar relationships to disability and cognitive dysfunction in MS, highlighting the potential of these techniques in clinical datasets.

Robustness of radiomics to variations in segmentation methods in multimodal brain MRI.

Radiomics in neuroimaging uses fully automatic segmentation to delineate the anatomical areas for which radiomic features are computed. However, differences among these segmentation methods affect radiomic features to an unknown extent. A scan-rescan dataset (n = 46) of T1-weighted and diffusion tensor images was used. Subjects were split into a sleep-deprivation and a control group. Scans were segmented using four segmentation methods from which radiomic features were computed. First, we measured segmentation agreement using the Dice-coefficient. Second, robustness and reproducibility of radiomic features were measured using the intraclass correlation coefficient (ICC). Last, difference in predictive power was assessed using the Friedman-test on performance in a radiomics-based sleep deprivation classification application. Segmentation agreement was generally high (interquartile range = 0.77-0.90) and median feature robustness to segmentation method variation was higher (ICC > 0.7) than scan-rescan reproducibility (ICC 0.3-0.8). However, classification performance differed significantly among segmentation methods (p < 0.001) ranging from 77 to 84%. Accuracy was higher for more recent deep learning-based segmentation methods. Despite high agreement among segmentation methods, subtle differences significantly affected radiomic features and their predictive power. Consequently, the effect of differences in segmentation methods should be taken into account when designing and evaluating radiomics-based research methods.

Unsupervised Deep Learning for Stroke Lesion Segmentation on Follow-up CT Based on Generative Adversarial Networks.

BACKGROUND AND PURPOSE: Supervised deep learning is the state-of-the-art method for stroke lesion segmentation on NCCT. Supervised methods require manual lesion annotations for model development, while unsupervised deep learning methods such as generative adversarial networks do not. The aim of this study was to develop and evaluate a generative adversarial network to segment infarct and hemorrhagic stroke lesions on follow-up NCCT scans. MATERIALS AND METHODS: Training data consisted of 820 patients with baseline and follow-up NCCT from 3 Dutch acute ischemic stroke trials. A generative adversarial network was optimized to transform a follow-up scan with a lesion to a generated baseline scan without a lesion by generating a difference map that was subtracted from the follow-up scan. The generated difference map was used to automatically extract lesion segmentations. Segmentation of primary hemorrhagic lesions, hemorrhagic transformation of ischemic stroke, and 24-hour and 1-week follow-up infarct lesions were evaluated relative to expert annotations with the Dice similarity coefficient, Bland-Altman analysis, and intraclass correlation coefficient. RESULTS: The median Dice similarity coefficient was 0.31 (interquartile range, 0.08-0.59) and 0.59 (interquartile range, 0.29-0.74) for the 24-hour and 1-week infarct lesions, respectively. A much lower Dice similarity coefficient was measured for hemorrhagic transformation (median, 0.02; interquartile range, 0-0.14) and primary hemorrhage lesions (median, 0.08; interquartile range, 0.01-0.35). Predicted lesion volume and the intraclass correlation coefficient were good for the 24-hour (bias, 3 mL; limits of agreement, -64-59 mL; intraclass correlation coefficient, 0.83; 95% CI, 0.78-0.88) and excellent for the 1-week (bias, -4 m; limits of agreement,-66-58 mL; intraclass correlation coefficient, 0.90; 95% CI, 0.83-0.93) follow-up infarct lesions. CONCLUSIONS: An unsupervised generative adversarial network can be used to obtain automated infarct lesion segmentations with a moderate Dice similarity coefficient and good volumetric correspondence.

Assessment of data consistency through cascades of independently recurrent inference machines for fast and robust accelerated MRI reconstruction.

Objective.Machine Learning methods can learn how to reconstruct magnetic resonance images (MRI) and thereby accelerate acquisition, which is of paramount importance to the clinical workflow. Physics-informed networks incorporate the forward model of accelerated MRI reconstruction in the learning process. With increasing network complexity, robustness is not ensured when reconstructing data unseen during training. We aim to embed data consistency (DC) in deep networks while balancing the degree of network complexity. While doing so, we will assess whether either explicit or implicit enforcement of DC in varying network architectures is preferred to optimize performance.Approach.We propose a scheme called Cascades of Independently Recurrent Inference Machines (CIRIM) to assess DC through unrolled optimization. Herein we assess DC both implicitly by gradient descent and explicitly by a designed term. Extensive comparison of the CIRIM to compressed sensing as well as other Machine Learning methods is performed: the End-to-End Variational Network (E2EVN), CascadeNet, KIKINet, LPDNet, RIM, IRIM, and UNet. Models were trained and evaluated on T1-weighted and FLAIR contrast brain data, and T2-weighted knee data. Both 1D and 2D undersampling patterns were evaluated. Robustness was tested by reconstructing 7.5× prospectively undersampled 3D FLAIR MRI data of multiple sclerosis (MS) patients with white matter lesions.Main results.The CIRIM performed best when implicitly enforcing DC, while the E2EVN required an explicit DC formulation. Through its cascades, the CIRIM was able to score higher on structural similarity and PSNR compared to other methods, in particular under heterogeneous imaging conditions. In reconstructing MS patient data, prospectively acquired with a sampling pattern unseen during model training, the CIRIM maintained lesion contrast while efficiently denoising the images.Significance.The CIRIM showed highly promising generalization capabilities maintaining a very fair trade-off between reconstructed image quality and fast reconstruction times, which is crucial in the clinical workflow.

Recurrent inference machines as inverse problem solvers for MR relaxometry.

In this paper, we propose the use of Recurrent Inference Machines (RIMs) to perform T1 and T2 mapping. The RIM is a neural network framework that learns an iterative inference process based on the signal model, similar to conventional statistical methods for quantitative MRI (QMRI), such as the Maximum Likelihood Estimator (MLE). This framework combines the advantages of both data-driven and model-based methods, and, we hypothesize, is a promising tool for QMRI. Previously, RIMs were used to solve linear inverse reconstruction problems. Here, we show that they can also be used to optimize non-linear problems and estimate relaxometry maps with high precision and accuracy. The developed RIM framework is evaluated in terms of accuracy and precision and compared to an MLE method and an implementation of the Residual Neural Network (ResNet). The results show that the RIM improves the quality of estimates compared to the other techniques in Monte Carlo experiments with simulated data, test-retest analysis of a system phantom, and in-vivo scans. Additionally, inference with the RIM is 150 times faster than the MLE, and robustness to (slight) variations of scanning parameters is demonstrated. Hence, the RIM is a promising and flexible method for QMRI. Coupled with an open-source training data generation tool, it presents a compelling alternative to previous methods.

Individual white matter bundle trajectories are associated with deep brain stimulation response in obsessive-compulsive disorder.

BACKGROUND: The ventral anterior limb of the internal capsule (vALIC) is a target for deep brain stimulation (DBS) in obsessive-compulsive disorder (OCD). Conventional surgical planning is based on anatomical landmarks. OBJECTIVE/HYPOTHESIS: We hypothesized that treatment response depends on the location of the active DBS contacts with respect to individual white matter bundle trajectories. This study thus aimed to elucidate whether vALIC DBS can benefit from bundle-specific targeting. METHODS: We performed tractography analysis of two fiber bundles, the anterior thalamic radiation (ATR) and the supero-lateral branch of the medial forebrain bundle (MFB), using diffusion-weighted magnetic resonance imaging (DWI) data. Twelve patients (10 females) who had received bilateral vALIC DBS for at least 12 months were included. We related the change in OCD symptom severity on the Yale-Brown obsessive-compulsive scale (Y-BOCS) between baseline and one-year follow-up with the distances from the active contacts to the ATR and MFB. We further analyzed the relation between treatment response and stimulation sites in standard anatomical space. RESULTS: We found that active stimulation of the vALIC closer to the MFB than the ATR was associated with better treatment outcome (p = 0.04; r2 = 0.34). In standard space, stimulation sites were largely overlapping between treatment (non)responders, suggesting response is independent of the anatomically defined electrode position. CONCLUSION: These findings suggest that vALIC DBS for OCD may benefit from MFB-specific implantation and highlight the importance of corticolimbic connections in OCD response to DBS. Prospective investigation is necessary to validate the clinical use of MFB targeting.

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling.

BACKGROUND AND PURPOSE: White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit. MATERIALS AND METHODS: In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively. We compared white matter hyperintensity CBF, normal-appearing white matter CBF, and GM CBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression. RESULTS: Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized ß = -0.248, P = .001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized ß = -0.065, P = .643) or GM CBF (standardized ß = -0.035, P = .382) in linear regression. CONCLUSIONS: Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit.

Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis.

BACKGROUND: Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors. METHOD: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC. RESULTS: Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA. CONCLUSIONS: UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.

Ultrasonography is not more reliable than anthropometry for assessing visceral fat in obese children.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Visceral fat accumulation is a risk factor for obesity-related complications. Waist circumference is used in clinical practice to assess visceral adiposity. WHAT THIS STUDY ADDS: Ultrasound is not superior to waist circumference for assessing visceral obesity in obese children. The optimal site for measuring waist circumference in obese children is at the smallest body circumference between xiphisternum and umbilicus. OBJECTIVE: Visceral fat accumulation is a well-established risk factor for obesity-related complications. In children, it has not been determined whether ultrasonography is superior to waist measurement for assessing visceral fat. Moreover, the optimal site for waist measurement has not been determined. DESIGN: In a prospective cohort of 92 severely obese children and adolescents (age 13.9 ± 2.2 years, body mass index z-score 3.29 ± 0.33), we evaluated the performance of ultrasonography and two different methods of waist circumference measurement, using magnetic resonance imaging as the reference standard. RESULTS: Waist circumference, defined as the smallest body circumference between xiphisternum and umbilicus had the strongest correlation with visceral fat quantity (r = 0.69 all, r = 0.68 girls, r = 0.64 boys). It was not outperformed by ultrasonography (r = 0.60 all, r = 0.62 girls, r = 0.50 boys) and correlated significantly better than the World Health Organization standard for waist measurement, midway between lower margin of the last rib and the crest of the ilium, (r = 0.51 all, r = 0.39 girls, r = 0.46 boys). CONCLUSIONS: Waist circumference measurement, defined as the smallest body circumference between xiphisternum and umbilicus, is the preferred non-invasive technique for daily clinical practice to assess visceral fat accumulation in severely obese children and adolescents. There is no place for ultrasonography for the quantification of visceral fat in this group.

Test-retest reliability of task-related pharmacological MRI with a single-dose oral citalopram challenge.

Non-invasive assessment of human neurotransmitter function is a highly valuable tool in clinical research. Despite the current interest in task-based pharmacological MRI (phMRI) for the assessment of neural correlates of serotonin (5-HT) function, test-retest reliability of this technique has not yet been established. Using a placebo-controlled crossover design, we aimed to examine the repeatability of task-related phMRI with a single dose of oral citalopram in twelve healthy female subjects. Since we were interested in the drug's effect on neural correlates of 5-HT related cognitive processes, a sensorimotor and an emotional face processing paradigm were used. For both paradigms, we found no significant effects of the oral citalopram challenge on task-positive brain activity with whole-brain analysis. With ROI-based analysis, there was a small effect of the challenge related to emotional processing in the amygdala, but this effect could not be reproduced between sessions. We did however find reproducible effects of the challenge on task-negative BOLD-responses, particularly in the medial frontal cortex and paracingulate gyrus. In conclusion, our data shows that a single oral dose of citalopram does not reliably affect emotional processing and sensorimotor activity, but does influence task-negative processes in the frontal cortex. This latter finding validates previous studies indicating a role for 5-HT in suppression of the task-negative network during goal-directed behavior.

Monoaminergic dysfunction in recreational users of dexamphetamine.

Preclinical studies suggest that dexamphetamine (dAMPH) can lead to monoaminergic neurotoxicity. This exploratory study aimed to investigate effects of recreational dAMPH use on the dopamine (DA) and noradrenaline (NA) systems in humans. To that purpose, eight male abstinent dAMPH (26.0 ± 4.0 years) users and 10 age- and IQ-matched male healthy control subjects (23.0 ± 3.8) underwent neuropsychological testing sensitive to DAergic function and single photon emission computed tomography (SPECT) scanning with [(123)I]FP-CIT to determine striatal DA transporter (DAT) binding. In addition, changes in cerebral blood flow (CBF) induced by the DA/NA reuptake inhibitor methylphenidate (MPH) were measured using pharmacological magnetic resonance imaging (phMRI). Performance of dAMPH users was significantly worse on executive function and verbal memory tasks. Striatal DAT binding ratios were on average lower in dAMPH users (near-significant, p=0.05). In addition, CBF in control subjects decreased significantly in response to MPH in gray matter and basal ganglia, among which the striatum, thalamus and hippocampus by 10% to 29%. However, in dAMPH users the CBF response was blunted in most brain areas studied, only decreasing in the hippocampus and orbitofrontal cortex. When comparing groups, CBF response was found to be significantly different in the thalamus with a decrease for healthy controls and a blunted response in dAMPH users. Collectively, our findings of a blunted hemodynamic response in monoaminergic regions, in combination with indications for lower striatal DAT binding and poorer behavioral measures are likely to represent DAergic dysfunction in dAMPH users, although NAergic dysfunction may also play a role.

Mapping the hemodynamic response in human subjects to a dopaminergic challenge with dextroamphetamine using ASL-based pharmacological MRI.

Pharmacological magnetic resonance imaging (phMRI) maps the neurovascular response to a pharmacological challenge and is increasingly used to assess neurotransmitter systems. Here we investigated the hemodynamic response to a dopaminergic (DAergic) challenge with dextroamphetamine (dAMPH) in humans using arterial spin labeling (ASL) based phMRI. Twelve healthy male subjects aged 21.0years (±1.5) were included. We used a pseudo-continuous ASL sequence (40min) to quantify cerebral blood flow (CBF) and started dAMPH infusion (0.3mg/kg) after 10min. On another day, we measured baseline dopamine D2/3 receptor availability with [(123)I]IBZM single photon emission computed tomography (SPECT). Baseline measures on mood and impulsivity and subjective behavioral responses to dAMPH were obtained. CBF response was corrected for cardiovascular effects using an occipital cortex mask for internal reference. Corrected CBF (sCBF) was analyzed using ROI-based and voxel-based analysis, in addition to independent component analysis (ICA). CBF data was correlated to D2/3 receptor availability and behavioral measures. Subjects reported experiencing euphoria following dAMPH administration. In the striatum sCBF significantly increased, as demonstrated by all three analysis methods. Voxel-based analysis and ICA also showed increased sCBF in the thalamus, anterior cingulate and cerebellum. Decreased sCBF was observed in several cortical areas, the posterior cingulated and paracingulate cortex. Apart from one ICA component, no correlations were found with sCBF changes and D2/3 receptor availability and behavioral measures. Our observations are in line with literature and provide further evidence that ASL-based phMRI with dAMPH is a promising technique to assess DAergic function in human subjects.

Feasibility of ASL-based phMRI with a single dose of oral citalopram for repeated assessment of serotonin function.

Assessment of cerebral serotonin (5-HT) function with arterial spin labeling (ASL)-based pharmacological magnetic resonance imaging (phMRI) could be a highly useful tool in clinical psychiatric research. The goal of this study was to verify the reliability of ASL-based phMRI after an oral challenge of a selective serotonin reuptake inhibitor (SSRI) in repeated assessment of cerebral 5-HT function. In a placebo-controlled, within-subject crossover study we investigated the effect of a single oral dose of citalopram on brain cerebral blood flow (CBF) using a pulsed ASL sequence (PASL) in twelve female healthy volunteers. The within-session repeatability of the PASL signal was good for all regions tested (wsCV<15%). Both ROI- and voxel-based analyses revealed small but significant effects of a citalopram challenge on CBF values in 5-HT rich brain regions, among which the frontal gyrus and thalamus. These effects could however not be replicated between sessions, most probably due to the small effect size of the oral citalopram challenge on cerebral blood flow. We therefore conclude that the test-retest reliability of PASL phMRI with an oral citalopram challenge is low, limiting the technique's sensitivity to time-dependent changes and consequently its use as a (clinical) research tool.

Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease.

OBJECTIVES: To prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. METHODS: Patients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of gadobutrol, single shot fast spin echo sequence and 3D T1-weighted spoiled gradient echo sequence, a dynamic coronal 3D T1-weighted fast spoiled gradient were performed before and after gadobutrol. Maximum enhancement (ME) and initial slope of increase (ISI) were calculated for four colon segments (ascending colon+coecum, transverse colon, descending colon+sigmoid, rectum) and (neo)terminal ileum. C-reactive protein (CRP), Crohn's disease activity index (CDAI), per patient and per segment Crohn's disease endoscopic index of severity (CDEIS) and disease duration were determined. Mean values of the (DCE-)MRI parameters in each segment from each patient were compared between four disease activity groups (normal mucosa, non-ulcerative lesions, mild ulcerative and severe ulcerative disease) with Mann-Whitney test with Bonferroni adjustment. Spearman correlation coefficients were calculated for continuous variables. RESULTS: Thirty-three patients were included (mean age 37 years; 23 females, median CDEIS 4.4). ME and ISI correlated weakly with segmental CDEIS (r=0.485 and r=0.206) and ME per patient correlated moderately with CDEIS (r=0.551). ME was significantly higher in segments with mild (0.378) or severe (0.388) ulcerative disease compared to normal mucosa (0.304) (p<0.001). No ulcerations were identified at conventional sequences. ME correlated with disease duration in diseased segments (r=0.492), not with CDAI and CRP. CONCLUSIONS: DCE-MRI can be used as a method for detecting Crohn's disease ulcerative lesions.

Mapping serotonergic dysfunction in MDMA (ecstasy) users using pharmacological MRI.

3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to induce loss of brain serotonin (5-HT) neurons. The purpose of this study was to determine the usefulness of pharmacological magnetic resonance imaging (phMRI) in assessing 5-HT dysfunction by examining the hemodynamic response evoked by infusion with the selective 5-HT reuptake inhibitor citalopram. We studied the effects of MDMA on brain hemodynamics using arterial spin labeling (ASL) based phMRI following a citalopram challenge (7.5mg/kg, i.v.), combined with [¹²³I]ß-CIT SPECT imaging in ten male MDMA users and seven healthy non-users. Single photon emission computed tomography (SPECT) imaging was used to assess the availability of 5-HT transporters (SERT). Imaging results were compared with the results of behavioral measures and mood changes following drug administration, in both groups (using the Beck Depression Inventory, Barratt Impulsiveness Scale and a visual analog scale). Reductions in SERT binding were observed in the occipital cortex of MDMA users. In line with this, citalopram induced decreases in cerebral blood flow (CBF) in the occipital cortex of MDMA users. ASL based phMRI also detected a CBF decrease in the thalamus of MDMA users. In concordance with imaging findings, behavioral measures differed significantly between MDMA users and controls. MDMA users had higher impulsivity scores and felt more uncomfortable after citalopram infusion, compared with control subjects. Our findings indicate that phMRI is very well suited for in-vivo assessment of 5-HT dysfunction.

Shaving diffusion tensor images in discriminant analysis: a study into schizophrenia.

A technique called 'shaving' is introduced to automatically extract the combination of relevant image regions in a comparative study. No hypothesis is needed, as in conventional pre-defined or expert selected region of interest (ROI)-analysis. In contrast to traditional voxel based analysis (VBA), correlations within the data can be modeled using principal component analysis (PCA) and linear discriminant analysis (LDA). A study into schizophrenia using diffusion tensor imaging (DTI) serves as an application. Conventional VBA found a decreased fractional anisotropy (FA) in a part of the genu of the corpus callosum and an increased FA in larger parts of white matter. The proposed method reproduced the decrease in FA in the corpus callosum and found an increase in the posterior limb of the internal capsule and uncinate fasciculus. A correlation between the decrease in the corpus callosum and the increase in the uncinate fasciculus was demonstrated.