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Diffusion-weighted magnetic resonance imaging (dMRI) of brain has helped elucidate the microstructural changes of psychiatric and neurodegenerative disorders. Inconsistency between MRI models has hampered clinical application of dMRI-based metrics. Using harmonized dMRI data of 300 scans from 69 traveling subjects (TS) scanning the same individuals at multiple conditions with 13 MRI models and 2 protocols, the widely-used metrics such as diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) were evaluated before and after harmonization with a combined association test (ComBat) or TS-based general linear model (TS-GLM). Results showed that both ComBat and TS-GLM significantly reduced the effects of the MRI site, model, and protocol for diffusion metrics while maintaining the intersubject biological effects. The harmonization power of TS-GLM based on TS data model is more powerful than that of ComBat. In conclusion, our research demonstrated that although ComBat and TS-GLM harmonization approaches were effective at reducing the scanner effects of the site, model, and protocol for DTI and NODDI metrics in WM, they exhibited high retainability of biological effects. Therefore, we suggest that, after harmonizing DTI and NODDI metrics, a multisite study with large cohorts can accurately detect small pathological changes by retaining pathological effects.

Purpose: The method of diffusion tensor image analysis along the perivascular space (DTI-ALPS) was gathering attention to evaluate the brain's glymphatic function or interstitial fluid dynamics. However, to the best knowledge, no study was conducted on the reproducibility of these automated methods for ALPS index values. Therefore, the current study evaluated the ALPS index reproducibility based on DTI-ALPS using two major automated calculation techniques in scan and rescan of the same subject on the same day., Materials and Methods: This study included 23 participants, including 2 with Alzheimer's disease, 15 with mild cognitive impairment, and 6 with cognitive normals. Scan and rescan data of diffusion magnetic resonance images were obtained, as well as automatically index for ALPS (ALPS index) and ALPS index maintaining tensor vector orientation information (vALPS index) with region of interest on the template fractional anisotropy map calculated by FSL software.These ALPS indices were compared in terms of scan and rescan reproducibility., Results: The absolute difference in ALPS-index values between scan and rescan was larger in the ALPS index than in the vALPS index by approximately 0.6% as the relative difference. Cohen's d for the left and right ALPS indices between methods were 0.121 and 0.159, respectively., Conclusion: The vALPS index based on DTI-ALPS maintaining tensor vector orientation information has higher reproducibility than the ALPS index. This result encourages a multisite study on the ALPS index with a large sample size and helps detect a subtle pathological change in the ALPS index., (© 2023. The Author(s) under exclusive licence to Japan Radiological Society.)

Childhood maltreatment is associated with altered brain structure and function and is a major risk factor for psychopathology, including reactive attachment disorder (RAD). However, whether changes to white matter microstructural integrity are associated with RAD is unclear. We used diffusion tensor imaging (DTI) to assess group differences in fractional anisotropy (FA) in patients with RAD (n = 25; mean age = 13.2) to typically developing (TD) controls (n = 33; mean age = 13.0). To further interpret differences in FA, additional parameters such as mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were assessed. We found that FA values in the body of corpus callosum (CC) and in the projection and thalamic pathways, including the posterior limb of the internal capsule and corona radiata (anterior, posterior, and superior), were significantly higher in the RAD than in the TD group. Additionally, RAD group showed significantly lower RD values in the body of the CC and abovementioned pathways than TD group. Our findings indicate that RAD is associated with altered structure of the CC and projection and thalamic pathways, which may play a role in emotion regulation. The aberrant development of these tracts in RAD may reflect stress-related psychophysiological responses., Competing Interests: Conflict of interest None, (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The functional connectivity of the default mode network (DMN) decreases in patients with Alzheimer's disease (AD) as well as in patients with type 2 diabetes mellitus (T2DM). Altered functional connectivity of the DMN is associated with cognitive impairment. T2DM is a known cause of cognitive dysfunction and dementia in the elderly, and studies have established that T2DM is a risk factor for AD. In addition, recent studies with positron emission tomography demonstrated that increased plasma glucose levels decrease neuronal activity, especially in the precuneus/posterior cingulate cortex (PC/PCC), which is the functional core of the DMN. These findings prompt the question of how increased plasma glucose levels decrease neuronal activity in the PC/PCC. Given the association among DMN, AD, and T2DM, we hypothesized that increased plasma glucose levels decrease the DMN functional connectivity, thus possibly reducing PC/PCC neuronal activity. We conducted this study to test this hypothesis., Results: Twelve young, healthy participants without T2DM and insulin resistance were enrolled in this study. Each participant underwent resting-state functional magnetic resonance imaging in both fasting and glucose loading conditions to evaluate the DMN functional connectivity. The results showed that the DMN functional connectivity in the PC/PCC was significantly lower in the glucose loading condition than in the fasting condition (P = 0.014)., Conclusions: Together with previous findings, the present results suggest that decreased functional connectivity of the DMN is possibly responsible for reduced PC/PCC neuronal activity in healthy individuals with increased plasma glucose levels.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects extensive regions of the central nervous system. In this work, we evaluated the structural connectome of patients with PD, as mapped by diffusion-weighted MRI tractography and a multi-shell, multi-tissue (MSMT) constrained spherical deconvolution (CSD) method to increase the precision of tractography at tissue interfaces. The connectome was mapped with probabilistic MSMT-CSD in 21 patients with PD and in 21 age- and gender-matched controls. Mapping was also performed by deterministic single-shell, single tissue (SSST)-CSD tracking and probabilistic SSST-CSD tracking for comparison. A support vector machine was trained to predict diagnosis based on a linear combination of graph metrics. We showed that probabilistic MSMT-CSD could detect significantly reduced global strength, efficiency, clustering, and small-worldness, and increased global path length in patients with PD relative to healthy controls; by contrast, probabilistic SSST-CSD only detected the difference in global strength and small-worldness. In patients with PD, probabilistic MSMT-CSD also detected a significant reduction in local efficiency and detected clustering in the motor, frontal temporoparietal associative, limbic, basal ganglia, and thalamic areas. The network-based statistic identified a subnetwork of reduced connectivity by MSMT-CSD and probabilistic SSST-CSD in patients with PD, involving key components of the cortico-basal ganglia-thalamocortical network. Finally, probabilistic MSMT-CSD had superior diagnostic accuracy compared with conventional probabilistic SSST-CSD and deterministic SSST-CSD tracking. In conclusion, probabilistic MSMT-CSD detected a greater extent of connectome pathology in patients with PD, including those with cortico-basal ganglia-thalamocortical network disruptions. Connectome analysis based on probabilistic MSMT-CSD may be useful when evaluating the extent of white matter connectivity disruptions in PD.

Background Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that reflects the Brownian motion of water molecules constrained within brain tissue. Fractional anisotropy (FA) is one of the most commonly measured DTI parameters, and can be applied to quantitative analysis of white matter as tract-based spatial statistics (TBSS) and voxel-wise analysis. Purpose To show an association between metallic implants and the results of statistical analysis (voxel-wise group comparison and TBSS) for fractional anisotropy (FA) mapping, in DTI of healthy adults. Material and Methods Sixteen healthy volunteers were scanned with 3-Tesla MRI. A magnetic keeper type of dental implant was used as the metallic implant. DTI was acquired three times in each participant: (i) without a magnetic keeper (FAnon1); (ii) with a magnetic keeper (FAimp); and (iii) without a magnetic keeper (FAnon2) as reproducibility of FAnon1. Group comparisons with paired t-test were performed as FAnon1 vs. FAnon2, and as FAnon1 vs. FAimp. Results Regions of significantly reduced and increased local FA values were revealed by voxel-wise group comparison analysis (a P value of less than 0.05, corrected with family-wise error), but not by TBSS. Conclusion Metallic implants existing outside the field of view produce artifacts that affect the statistical analysis (voxel-wise group comparisons) for FA mapping. When statistical analysis for FA mapping is conducted by researchers, it is important to pay attention to any dental implants present in the mouths of the participants.

Purpose: Various magnetic resonance imaging (MRI) techniques including T 2 *-weighted imaging, susceptibility-weighted imaging, and MR relaxometry had been performed to evaluate different patterns of brain iron depositions in Parkinsonian syndrome. The aim of the present study was to evaluate the diagnostic value of a volume of interest (VOI) analysis on the principles of echo shifting with a train of observations (PRESTO) imaging using the statistical parametric mapping (SPM) 8 and the WFU PickAtlas program for the diagnosis of Parkinsonian syndrome.,Methods: Fifty subjects, including 13 with the Parkinsonian variant of multiple system atrophy (MSA-P), 12 with progressive supranuclear palsy (PSP), 12 with Parkinson's disease (PD) and 13 controls were evaluated in this study. After the spatial normalization of PRESTO images on SPM8, the WFU PickAtlas program was performed to create target VOIs in the putamen, red nucleus, substantia nigra, subthalamic nucleus, and dentate nucleus. The signal intensity ratio (SIR) was calculated by normalizing the signal of each VOI to that of the cerebrospinal fluid space. These SIRs were used as determinants in receiver operating characteristic (ROC) analyses., Results: SIR of the putamen was significantly lower in MSA-P than in PSP (P = 0.0051) and controls (P = 0.0004). In contrast, SIR of the red nucleus was significantly lower in PSP than in MSA-P (P = 0.0003), PD (P = 0.0029), and controls (P = 0.0011). In ROC analyses, SIR of the putamen exhibited the highest areas under the curves (AUCs) of 0.83 (vs. PSP) and 0.91 (vs. controls) in the diagnosis of MSA-P. On the other hand, SIR of the red nucleus exhibited the highest AUCs of 0.87 (vs. MSA-P), 0.90 (vs. PD), and 0.89 (vs. controls) in the diagnosis of PSP., Conclusions: The VOI analysis based on spatially normalized PRESTO images may be useful for depicting hypointensity, indicative of abnormal iron depositions, of the putamen and red nucleus in the diagnosis of MSA-P and PSP.

We investigated the clinical predictors of the degree of recovery in patients with prolonged disorders of consciousness (PDC) caused by traumatic brain injury. Fourteen patients with PDC underwent two diffusion tensor imaging (DTI) studies; the first and second scans were performed at 345.6 ± 192.6 and 689.1 ± 272.2 days after the injury, respectively. In addition to the temporal changes in each of these diffusion parameters, fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity were assessed over a 1-year period. Relationship of clinical and DTI parameters with recovery from PDC (RPDC) was evaluated using Spearman's rank-correlation and stepwise multiple linear regression analysis. The mean FA and number of voxels with FA values > 0.4 (VsFA0.4) were significantly decreased at the second scan. A significant positive correlation was observed between the degree of RPDC and mean FA ( r = 0.60) and VsFA0.4 ( r = 0.68) as well as between the difference in VsFA0.4 ( r = 0.63) and AD ( r = 0.54) between the first and second scans. On multiple linear regression analysis, initial severity of PDC and the difference in AD remained significantly associated with the degree of RPDC. The microstructural white matter changes observed in this study indicate their potential relation with the degree of RPDC over the longer term., Competing Interests: The authors declare that they have no competing interests.

Magnetic resonance diffusion tensor imaging (DTI) is a noninvasive technique that can identify and quantify white matter tracts by evaluating the diffusion of water in biological tissues. While association fibers are bundles of axons within the brain that unite different parts of the same cerebral hemisphere, projection fibers are bundles of axons that unite the cortex with lower parts of the brain and the spinal cord. The commissural fibers are axon bundles that connect the two hemispheres of the brain. Quantitative analysis of DTI can be roughly classified into three types: region of interest analysis, tract-specific analysis, and fully automated hypothesis free whole brain analysis.

Background: Evidence supports disruption in white matter (WM) connectivity in established schizophrenia, however, it is unclear when these abnormalities occur during the course of illness and if they are progressive. Here we investigated whether WM abnormalities predate illness onset by examining a group of individuals with an 'at risk mental state' (ARMS) and assess whether there is evidence of progressive change. We hypothesized that WM abnormalities are associated with symptom change., Methods: Sixteen healthy controls and 41 ARMS subjects at baseline underwent Diffusion Tensor Imaging (DTI). Sub-threshold positive symptoms were measured using the Scale of Prodromal Symptoms (SOPS). Imaging and symptoms were re-administered in the ARMS group after one year (52weeks). Fractional anisotropy (FA) value differences between ARMS and control groups at baseline were localized using the method of Tract-Based Spatial Statistics (TBSS)., Results: At baseline, FA was significantly reduced in a sub-region of the corpus callosum (CC) in the ARMS group as a whole compared to controls. This reduction was also found in the 34 individuals who did not transition (ARMS-N) during the one-year follow-up. However, the ARMS-N group showed a significant improvement in sub-threshold positive symptoms at follow-up, which was correlated with an increase in FA in the same CC region (r=-0.664, p<0.001)., Discussion: There was a significant FA reduction in the CC in individuals at high risk for psychosis regardless of transition status at one year. This suggests that WM abnormalities in the CC may represent a biological vulnerability to psychosis. Improvement in sub-threshold positive symptoms was associated with improvement in measures of WM integrity in the CC. This may suggest that neurobiological 'resilience' is associated with improved outcomes, although this notion requires future study., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We report the intersite scan reliability of diffusion tensor imaging (DTI) parameters using identical 3T scanners and acquisition protocols at 2 sites. Voxel-based analysis revealed several regions with significant intersite differences. The intersite reliability of DTI measures showed coefficients of variation below 4% in tract-specific analysis (TSA) and below 6% in atlas-based analysis. Given the excellent reliability of TSA, our results suggest it as a promising and useful tool for multicenter DTI studies.

Introduction: Diffusional kurtosis imaging (DKI) is a more sensitive technique than conventional diffusion tensor imaging (DTI) for assessing tissue microstructure. In particular, it quantifies the microstructural integrity of white matter, even in the presence of crossing fibers. The aim of this preliminary study was to compare how DKI and DTI show white matter alterations in Parkinson disease (PD)., Methods: DKI scans were obtained with a 3-T magnetic resonance imager from 12 patients with PD and 10 healthy controls matched by age and sex. Tract-based spatial statistics were used to compare the mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) maps of the PD patient group and the control group. In addition, a region-of-interest analysis was performed for the area of the posterior corona radiata and superior longitudinal fasciculus (SLF) fiber crossing., Results: FA values in the frontal white matter were significantly lower in PD patients than in healthy controls. Reductions in MK occurred more extensively throughout the brain: in addition to frontal white matter, MK was lower in the parietal, occipital, and right temporal white matter. The MK value of the area of the posterior corona radiata and SLF fiber crossing was also lower in the PD group., Conclusion: DKI detects changes in the cerebral white matter of PD patients more sensitively than conventional DTI. In addition, DKI is useful for evaluating crossing fibers. By providing a sensitive index of brain pathology in PD, DKI may enable improved monitoring of disease progression.

Purpose: Hypertension is associated with substantial morbidity in Japan. The aim of this work was to evaluate whether hypertension is associated with white matter microstructural changes by using diffusional kurtosis imaging (DKI)., Methods: We explored the regional patterns of white matter alteration in 15 hypertensive middle-aged male participants and 11 normotensive controls by using DKI-based whole-brain analysis. In addition, we investigated whether the observed white matter microstructural changes were related to systolic or diastolic blood pressure by using Pearson's correlation coefficient analysis., Results: Mean diffusional kurtosis (MDK) values were significantly higher in hypertensive participants than in normotensive participants (P < 0.05; family-wise error correction for multiple comparisons), indicating widespread microstructural changes in white matter. Moreover, we noted a statistically significant positive correlation between systolic and diastolic blood pressure and MDK values of the whole brain., Conclusion: Our study suggests that microstructural white matter changes occur in middle-aged men with hypertension, even before the onset of cerebrovascular disease. Thus, DKI might be used as a screening tool for risk of cerebrovascular disease. This highlights the need to further elucidate the relationship between hypertension and DKI of the brain.

Diffusional kurtosis imaging (DKI) is a new technique based on non-Gaussian water diffusion analysis. However, the original DKI protocol (six b values and 30 motion-probing gradient (MPG) directions) requires more than 10 min of scanning time, which is too long for daily clinical use. We aimed to find suitable b value, MPG direction, and diffusion time settings for faster DKI. Four normal healthy subjects participated in the study. All DKI data sets were acquired on a clinical 3T-MRI scanner (Philips Medical Systems) with use of three protocols of 0-7500 s/mm(2) b values, 6-32 MPG directions, and 23-80 ms diffusion time. There was a remarkable difference in the standard deviation (SD) of the mean DK values in the number of MPG directions. The mean DK values were significantly higher in the posterior limb of the internal capsule (p = 0.003, r = 0.924) and thalamus (p = 0.005, r = 0.903), whereas the mean DK values of the cerebrospinal fluid (CSF) (p = 0.001, r = -0.976) were significantly lower when we used a longer diffusion time. Our results indicate that the SD of the mean DK values was higher in 15 MPG directions than in 20 MPG directions and more. Because the mean DK values of the CSF were significantly lower when we used longer diffusion times, we expect longer diffusion times to be useful for DKI. We propose the following imaging parameters for clinical use: 0, 1000, and 2000 s/mm(2) b values; 20 MPG directions; Δ/δ 45.3/13.3 ms.

Objective: We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI., Research Design and Methods: Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF., Results: In the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = -0.56, P < 0.04)., Conclusions: Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.

Background: Depression in old age is an increasing contributor to poor health and accompanying health care costs. Although there is an abundance of literature on later-life depression (LLD), the neural correlates have not been clarified. The aim of this study was to determine whether patients with LLD show abnormal gray matter volume (GMV) and white matter integrity by using multiple image analysis methods.Methods: The study included 45 patients with LLD and 61 healthy participants who were matched for age, sex, years of education, and vascular risk factors. GMV was examined using voxel-based morphometry, while the white matter integrity was determined by tract-based spatial statistics and tract-specific analysis, which were obtained from high-resolution magnetic resonance images.Results: Patients with LLD showed significantly less GMV in the orbitofrontal cortex, anterior cingulate, insula, amygdala, and temporal regions, as well as higher fractional anisotropy in the uncinate fasciculus, compared with healthy participants. Patients with LLD who had reduced orbitofrontal and insular GMV had more severe clinical variables. The reduced orbitofrontal GMV was associated with higher fractional anisotropy in the uncinate fasciculus.Limitation: The effects of medication should also be considered when interpreting the results of this study.Conclusion: Our results suggest that regional GMV is linked to white matter integrity of the uncinate fasciculus in the orbitomedial prefrontal limbic network, and the disruption of this network may be involved in the pathophysiology of LLD. [ABSTRACT FROM AUTHOR]