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The glymphatic system (GS) is a whole-brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non-invasive methods based on magnetic resonance imaging (MRI) along with aquaporin-4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi-shell diffusion-weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF-AQP4. CSF-AQP4 levels and MRI measures-including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW-WM) and mean kurtosis (MK-WM), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) (mean, left and right)-were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF-AQP4 (exp(b) = 2.05, p = .005) and FW-WM FW-WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF-AQP4 and FW-WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK-WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF-AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPS-induced glial activation., Methods: Seven healthy male volunteers, (mean 25.3 ± 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-5½ hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter., Results: Body temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R 2  = 0.83; p = 0.004)., Conclusions: DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The reproducibility of Neurite orientation dispersion and density imaging (NODDI) metrics from time-saving multiband (MB) EPI compared with singleband (SB) has not been considered. This study aims to evaluate the reproducibility of NODDI parameters from SB and MB acquisitions, determine the agreement between acquisitions and estimate the sample sizes required to detect between-group change., Methods: Brain diffusion MRI data were acquired using SB and MB (acceleration factors 2 (MB2) and 3 (MB3)) on 8 healthy subjects on 2 separate visits. NODDI maps of isotropic volume fraction (FISO), neurite density (NDI) and orientation dispersion index (ODI) were estimated. Region-of-interest analysis was performed; variability across subjects and visits was measured using coefficients of variation (CoV). Intraclass correlation coefficient and Bland-Altman analysis were performed to assess reproducibility and detect any systematic bias between SB, MB2 and MB3. Power calculations were used to determine sample sizes required to detect group differences., Results: Both NDI and ODI were reproducible between visits; however, FISO was variable. All parameters were not reproducible across methods; a systematic bias was observed with the derived values decreasing as the MB factor increases. The number of subjects needed to detect a between-group change is not significantly different between methods; however, ODI needs considerably higher sample sizes than NDI., Conclusions: Both SB and MB yield highly reproducible NDI and ODI measures, but direct comparison of these parameters between methods is complicated by systematic differences that exist between the two approaches., (© 2020. The Author(s).)

Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. In susceptible patients, fatigue and motivational impairment emerge early and have been linked to changes in basal ganglia (striatal) metabolism, neurochemistry and microstructural integrity. Here we use neurite orientation dispersion and density imaging (NODDI) modeling of multi-shell diffusion MRI to investigate whether changes in orientation-dispersion index (ODI) or neurite density index (NDI) can predict the later emergence of IFN-α-induced fatigue. Eighteen patients initiating IFN-α-based treatment for hepatitis-C underwent diffusion MRI and blood sampling at baseline and 4 h after their first IFN-α injection. They were then followed up with regular psychological assessments for 12 weeks of treatment. IFN-α injection stimulated an acute inflammatory cytokine response and evoked acute fatigue that peaked between 4 and 12 weeks of treatment. Within the brain, IFN-α induced an acute increase in NDI in patients that experienced a simultaneous increase in IFN-α-induced fatigue but not in patients that did not. Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8 weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Microstructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterize the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections. Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'., (Copyright © 2018. Published by Elsevier Inc.)

In recent years the cerebellum has been attributed amore important role in higher-level functions than previously believed. We examined a cohort of patients suffering from cerebellar atrophy resulting in ataxia, with two main objectives: first to investigate which regions of the cerebrum were affected by the cerebellar degeneration, and second to assess whether diffusion magnetic resonance imaging (dMRI) metrics within the medial (MCP) and superior cerebellar peduncle (SCP) - namely fractional anisotropy (FA) and radial diffusivity (RD) - could be used as a biomarker in patients with this condition. Structural and dMRI data of seven patients with cerebellar atrophy (2 with spinocerebellar atrophy type 2, 1 with Friedreich's ataxia, 4 with idiopathic cerebellar ataxia) and no visible cortical lesions or cortical atrophy were investigated with Freesurfer and voxel-based morphometry (VBM) of gray matter (GM) as well as MCP and SCP FA maps. Correlations of MCP and SCP mean FA with ataxia scores and subscores were also evaluated. Freesurfer showed that patients had significantly reduced volume of the thalamus, ventral diencephalon and pallidum. VBM also demonstrated significantly lower local GM volumes in patients, notably in the head of the caudate nucleus, posterior cingulate gyrus and orbitofrontal cortex bilaterally, as well as in Broca's area in the left hemisphere, and a significant increase in RD in the MCP and SCP of both hemispheres. A significant correlation was found between MCP mean FA and total ataxia score (R=-0.7, p=0.03), and subscores for kinetic functions (R=-0.74, p=0.03) and oculomotor disorders (R=-0.70, p=0.04). The regions of the cerebrum found to have significantly lower local GM volumes have been described to be involved in higher-level cerebellar functions such as initiation of voluntary movements, emotional control, memory retrieval and general cognition. Our findings corroborate recent research pointing to a more extensive corticocerebellar system than previously thought. The significant difference in the MCP and SCP dMRI metrics between patients and controls as well as the significant correlation with ataxia total score and subscores support the use of dMRI metrics as an imaging biomarker for cerebellar degeneration and ataxia.

While methods of measuring non-invasively both, functional and structural brain connectivity are available, the degree of overlap between them is still unknown. In this paper this issue is addressed by investigating the connectivity pattern of a brain structure with many, well characterized structural connections, namely the thalamus. Diffusion-weighted and resting state (RS) functional MRI (fMRI) data were collected in a group of 38 healthy participants. Probabilistic tractography was performed to parcellate the thalamus into regions structurally connected to different cortical areas. The resulting regions were used as seeds for seed-based analysis of RS fMRI data. The tractographic parcellation was thus cross-validated against functional connectivity data by evaluating the overlap between the functional and structural thalamo-cortical connections originating from the parcellated regions. Our data show only a partial overall correspondence between structural and functional connections, in the same group of healthy individuals, thus suggesting that the two approaches provide complementary and not overlapping information. Future studies are warranted to extend the results we obtained in the thalamus to other structures, and to confirm that the mechanisms behind functional connectivity are more complex than just expressing structural connectivity.

Diffusion tensor imaging (DTI) tractography and image registration were used to investigate a patient with a massive left-sided brain tumor, whose size was largely disproportionate to his subtle neurological deficits. MRI was obtained from the patient and his healthy identical twin, who acted as anatomical reference for DTI and as a control for quantitative measures. To compensate for the patient's altered anatomy, seed and way points for probabilistic tractography were drawn on the color-coded direction maps of the healthy twin. Registration, based on the combination of b0-images, T2-weighted and T1-weighted images, was used to identify the corresponding regions in the patient. The corticospinal tract (CST), the superior longitudinal fasciculus (SLF), and the cingulum bundle (CB) showed displaced anatomy. A significant difference was found between fractional anisotropy distribution along the left SLF and CB, but not along the CST. These findings fit well with the patient's substantial preservation of his motor abilities, while abnormalities of the SLF and CB could explain the subtle but detectable cognitive deficits.

Obtaining reliable data and drawing meaningful and robust inferences from diffusion MRI can be challenging and is subject to many pitfalls. The process of quantifying diffusion indices and eventually comparing them between groups of subjects and/or correlating them with other parameters starts at the acquisition of the raw data, followed by a long pipeline of image processing steps. Each one of these steps is susceptible to sources of bias, which may not only limit the accuracy and precision, but can lead to substantial errors. This article provides a detailed review of the steps along the analysis pipeline and their associated pitfalls. These are grouped into 1 pre-processing of data; 2 estimation of the tensor; 3 derivation of voxelwise quantitative parameters; 4 strategies for extracting quantitative parameters; and finally 5 intra-subject and inter-subject comparison, including region of interest, histogram, tract-specific and voxel-based analyses. The article covers important aspects of diffusion MRI analysis, such as motion correction, susceptibility and eddy current distortion correction, model fitting, region of interest placement, histogram and voxel-based analysis. We have assembled 25 pitfalls (several previously unreported) into a single article, which should serve as a useful reference for those embarking on new diffusion MRI-based studies, and as a check for those who may already be running studies but may have overlooked some important confounds. While some of these problems are well known to diffusion experts, they might not be to other researchers wishing to undertake a clinical study based on diffusion MRI., (Copyright © 2010 John Wiley & Sons, Ltd.)

This article presents the potential problems arising from the use of "axial" and "radial" diffusivities, derived from the eigenvalues of the diffusion tensor, and their interpretation in terms of the underlying biophysical properties, such as myelin and axonal density. Simulated and in vivo data are shown. The simulations demonstrate that a change in "radial" diffusivity can cause a fictitious change in "axial" diffusivity and vice versa in voxels characterized by crossing fibers. The in vivo data compare the direction of the principle eigenvector in four different subjects, two healthy and two affected by multiple sclerosis, and show that the angle, alpha, between the principal eigenvectors of corresponding voxels of registered datasets is greater than 45 degrees in areas of low anisotropy, severe pathology, and partial volume. Also, there are areas of white matter pathology where the "radial" diffusivity is 10% greater than that of the corresponding normal tissue and where the direction of the principal eigenvector is altered by more than 45 degrees compared to the healthy case. This should strongly discourage researchers from interpreting changes of the "axial" and "radial" diffusivities on the basis of the underlying tissue structure, unless accompanied by a thorough investigation of their mathematical and geometrical properties in each dataset studied., ((c) 2009 Wiley-Liss, Inc.)

This article describes a novel approach for local estimation of the radial diffusion coefficient (D(perpendicular)) in white matter (WM) regions containing well-oriented nervous fibers. The method is based on the assumption that the diffusion process in well-organized WM regions responds to a cylindrical symmetry. The increased precision in the estimation of D(perpendicular) provided by this local approach compared to standard techniques based on diffusion tensor imaging is demonstrated using numerical simulations. An in vivo validation of the technique is also provided, showing its application to the corpus callosum of six healthy volunteers, highlighting the sensitivity of the method. Assuming that D(perpendicular) is sensitive to myelin integrity, our technique has the potential to investigate pathophysiological aspects of several neurological and psychiatric disorders with improved precision in targeted WM tracts.

Objectives: In bipolar disorder (BD), dysregulation of mood may result from white matter abnormalities that disrupt fronto-subcortical circuits. In this study, we explore such abnormalities using diffusion tensor imaging (DTI), an imaging technique capable of detecting subtle changes not visible with conventional magnetic resonance imaging (MRI), and voxel-based analysis., Methods: Thirty-six patients with BD, all but two receiving antidepressants or mood stabilizers, and 28 healthy controls matched for age and gender were studied. Diffusion-weighted echoplanar images (DW-EPI) were obtained using a 1.5T scanner. Voxel-based analysis was performed using SPM 2. Differences between the groups in mean diffusivity and fractional anisotropy (FA) were explored., Results: In the patient group, mean diffusivity was increased in the right posterior frontal and bilateral prefrontal white matter, while FA was decreased [corrected] in the inferior, middle temporal and middle occipital regions. The areas of increased mean diffusivity overlapped with those previously found to be abnormal using volumetric MRI and magnetization transfer imaging (MTI) in the same group of patients., Conclusions: White matter abnormalities, predominantly in the fronto-temporal regions, can be detected in patients with BD using DTI. The neuropathology of these abnormalities is uncertain, but neuronal and axonal loss, myelin abnormalities and alterations in axonal packing density are likely to be relevant. The neuroprotective effects of some antidepressants and mood stabilizers make it unlikely that medication effects could explain the abnormalities described here, although minor effects cannot be excluded.

Corticobasal degeneration (CBD) presents with symptoms that often overlap with other neurological conditions. In many cases, diagnosis, prognosis and consequent clinical management remain uncertain. Structural and functional asymmetric brain changes represent the most consistent imaging findings that may assist in CBD diagnosis. Diffusion Tensor MRI (DT-MRI) is a quantitative technique that allows microscopic tissue abnormalities to be non-invasively assessed in vivo. A single case of clinically suspected CBD with symmetric diffuse brain atrophy on conventional-MRI scans was studied using DT-MRI by voxel-wise comparison with eight healthy subjects. The lateralized distribution of DT-MRI abnormalities was consistent with clinical features providing a substantial support to the diagnosis.

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the clinical manifestations of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail and we present here a study of patients with first-episode psychosis using this technique. We selected the corpus callosum for this study because there is evidence that it is abnormal in schizophrenia. In addition, the topographical organization of its fibers makes it possible to relate focal abnormalities to specific cortical regions. Eighteen patients with first-episode psychosis and 21 healthy subjects took part in the study. A probabilistic tractography algorithm (PICo) was used to study fractional anisotropy (FA). Seed regions were placed in the genu and splenium to track fiber tracts traversing these regions, and a multi-threshold approach to study the probability of connection was used. Multiple linear regressions were used to explore group differences. FA, a measure of tract coherence, was reduced in tracts crossing the genu, and to a lesser degree the splenium, in patients compared with controls. FA was also lower in the genu in females across both groups, but there was no gender-by-group interaction. The FA reduction in patients may be due to aberrant myelination or axonal abnormalities, but the similar tract volumes in the two groups suggest that severe axonal loss is unlikely at this stage of the illness.

Purpose: To examine frontotemporal white-matter integrity in patients with temporal lobe epilepsy (TLE) and interictal psychosis., Method: Patients with TLE and interictal psychosis (IP; n = 20) were compared with age-matched TLE patients without psychosis (NIP; n = 20). Patients had either no focal lesions or hippocampal sclerosis on conventional MRI. Complete diffusion tensor imaging (DTI) data were available in 18 IP and 20 NIP patients. A region-of-interest (ROI) approach was used to determine the DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), in the middle frontal and middle temporal gyri. The relation between the DTI measures and neuropsychological tests previously identified as impaired in the IP group was examined., Results: The IP group had significantly lower FA values in both frontal and temporal regions and significantly higher MD in bilateral frontal regions. We found that performance on some neuropsychological tests was significantly related to frontotemporal FA reductions., Conclusions: Our findings suggest that subtle abnormalities in the frontotemporal white matter of patients with interictal psychosis may be undetectable on conventional MRI. These abnormalities may contribute to the cognitive deficits detected in these patients.

The aim of the present study was to apply diffusion tensor MRI (DT-MRI), a quantitative MRI measure which reflects tissue organization, to dementia with Lewy bodies (DLB). DT-MRI scans were obtained from 15 patients with probable DLB and 10 sex- and age-matched healthy controls. Abnormalities were found in the corpus callosum, pericallosal areas and the frontal, parietal, occipital and, less prominently, temporal white matter of patients compared with controls. Abnormalities were also found in the caudate nucleus and the putamen. The average grey matter volume was lower in patients than in controls. These findings of concomitant grey matter atrophy and white matter abnormalities (as detected by DT-MRI) in regions with a high prevalence of long connecting fibre tracts might suggest the presence of neurodegeneration involving associative cortices. The modest involvement of the temporal lobe fits with the relative preservation of global neuropsychological measures and memory tasks in the early stage of DLB. The selective involvement of parietal, frontal and occipital lobes might explain some of the clinical and neuropsychological features of DLB, providing a possible distinctive marker for this disease. The abnormalities found in the subcortical grey matter may indicate that DLB and Parkinson's disease share a similar nigrostriatal involvement caused by common pathophysiological mechanisms.

Voxel-based morphometry (VBM) has been used to analyze diffusion tensor MRI (DT-MRI) data in a number of studies. In VBM, following spatial normalization, data are smoothed to improve the validity of statistical inferences and to reduce inter-individual variation. However, the size of the smoothing filter used for VBM of DT-MRI data is highly variable across studies. For example, a literature review revealed that Gaussian smoothing kernels ranging in size (full width at half maximum) from zero to 16 mm have been used in DT-MRI VBM type studies. To investigate the effect of varying filter size in such analyses, whole brain DT-MRI data from 14 schizophrenic patients were compared with those of 14 matched control subjects using VBM, when the filter size was varied from zero to 16 mm. Within this range of smoothing, four different conclusions regarding apparent patient control differences could be made: (i) no significant patient-control differences; (ii) reduced FA in right superior temporal gyrus (STG) in patients; (iii) reduced FA in both right STG and left cerebellum in patients; and (iv) reduced FA only in left cerebellum in patients. These findings stress the importance of recognizing the effect of the matched filter theorem on VBM analyses of DT-MRI data. Finally, we investigated whether one of the underlying assumptions of parametric VBM, i.e., the normality of the residuals, is met. Our results suggest that, even with moderate smoothing, a large number of voxels within central white matter regions may have non-normally distributed residuals thus making valid statistical inferences with a parametric approach problematic in these areas.

Background: Neuropathological and imaging studies suggest that corpus callosum abnormalities (CC) are present in schizophrenia, but it remains to be determined whether these abnormalities are present at illness onset. Diffusion tensor imaging (DTI), which is more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle structural changes in the organisation and integrity of white matter tracts, is an ideal tool to investigate this question., Objective: To determine whether CC abnormalities are present at illness onset in schizophrenia., Methods: Twenty patients (14 men, six women) with first episode schizophrenia and 29 controls (11 men, 18 women) were studied. Both high resolution volumetric T1-weighted images and DTI were acquired. Regions of interest (ROI) were placed in the splenium and genu of the CC and fractional anisotropy (FA) and diffusivity (D) measured., Results: No differences in FA or D were detected in these regions between patients and controls. In women, irrespective of group membership, FA was significantly lower and there was a trend for D to be higher than in men, indicating less barriers to diffusion in females., Conclusion: The negative findings of this study suggest that in the early stages of schizophrenia there is no disruption to the integrity of the CC and raise the possibility that the neuropathological abnormalities may appear later and be progressive, at least in some patients.

The aim of this study was to apply sensitivity-encoding (SENSE) echo-planar imaging (EPI) to diffusion tensor MR imaging of the cervical cord, an anatomic region where MR imaging is particularly challenging. This technique was implemented with a SENSE reduction factor of 2 and used for imaging a water phantom and five healthy volunteers. Off-resonance artifacts were notably reduced compared with those of full-FOV EPI sequences. This approach to diffusion tensor MR imaging of the cervical cord is promising for future, more extensive clinical applications.

Background and Purpose: Diffusion tensor MR imaging has the potential to improve our ability to monitor several neurologic conditions. As a preliminary step to the assessment of the role of diffusion tensor MR imaging in the context of longitudinal and multicenter studies, we evaluated the effect of sequence-, imaging unit-, and imaging-reimaging-induced variations on diffusion tensor MR imaging quantities derived from histogram analysis of a large portion of the central brain of healthy volunteers., Methods: Each of eight healthy volunteers underwent imaging on two MR imaging units using three different pulsed gradient spin-echo single shot echo-planar pulse sequences (each of them having a different diffusion gradient scheme). Four additional healthy participants underwent imaging twice on the same imaging unit to assess imaging-reimaging variability., Results: For mean diffusivity histograms, the differences between inter-sequence and inter-imaging unit coefficients of variation were significant for all the considered quantities with P values ranging from.003 to <.001. Also, the inter-imaging unit coefficient of variation for average fractional anisotropy was significantly higher than the corresponding inter-sequence coefficient of variation (P =.002). In general, inter-sequence mean diffusivity histogram-derived metrics (coefficients of variation ranging from 1.72% to 5.56%) were more reproducible than were fractional anisotropy histogram-derived metrics (coefficients of variation ranging from 5.45% to 7.34%). Imaging-reimaging variability was found to fall in the range of inter-sequence coefficients of variation for all the considered quantities., Conclusion: This study shows that inter-sequence, imaging-reimaging, and inter-imaging unit variabilities of diffusion tensor MR imaging-derived measurements are relatively low, suggesting that diffusion tensor MR imaging might provide additional measures of outcome with which to assess the evolution of brain structural damage in large scale studies of various neurologic conditions.