Multiple sclerosis (MS), a demyelinating disease, occurs principally in the white matter (WM) of the central nervous system. Conventional magnetic resonance imaging (MRI) is sensitive to some, but not all, brain changes associated with MS. Diffusion-weighted imaging (DWI) provides information about water diffusion in tissue and diffusion tensor MRI (DT-MRI) about fiber direction, allowing for the identification of WM abnormalities that are not apparent on conventional MRI images. These techniques can quantitatively characterize the local microstructure of tissues. MS-associated disease processes lead to regions characterized by an increased amount of water diffusion and a decrease in the anisotropy of diffusion direction. These changes have been found to produce different patterns in MS patients presenting different courses of the disease. Changes in water diffusion may allow examination of the type, appearance, enhancement, and location of lesions not readily visible by other means. Ongoing studies of MS are integrating conventional MRI and DT-MRI measures with connectivity-based regional assessment, aiming to provide a better understanding of the nature and the location of WM lesions. This integration and the development of novel image-processing and visualization techniques may improve the understanding of WM architecture and its disruption in MS. This article presents a brief history of DWI, its basic principles and applications in the study of MS, a review of the properties and applications of DT-MRI, and their use in the study of MS. In addition, this article illustrates the methodology for the analysis of DT-MRI in ongoing studies of MS.

The problem of selecting a threshold for the statistical parameter maps in functional MRI (fMRI) is a delicate issue. The use of advanced test statistics and/or the complex dependence structure of fMRI noise may preclude parametric statistical methods for finding appropriate thresholds. Non-parametric statistical methodology has been presented as a feasible alternative. In this paper, we discuss resampling methods for finding thresholds in single subject fMRI analysis. It is shown that the presence of a BOLD response in the time series biases the estimation of the temporal autocorrelation, which in turn leads to biased thresholds. Therefore, proposed resampling methods based on Fourier and wavelet transforms, which employ implicit and weak models of the temporal noise characteristic, may produce erroneous thresholds. In contrast, resampling based on a pre-whitening transform, which is driven by an explicit noise model, is robust to the presence of a BOLD response. The size of the bias is, however, largely dependent on the complexity of the experimental design. While blocked designs can induce large biases, event-related designs generate significantly smaller biases. Results supporting these claims are provided.

BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman’s rho, followed by post hoc hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. CONCLUSIONS: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.

BACKGROUND: Advanced neuroimaging techniques have brought increasing recognition of cerebellar injury among premature infants. The developmental relationship between early brain injury and effects on the cerebrum and cerebellum remains unclear. OBJECTIVES: To examine whether cerebral parenchymal brain lesions among preterm infants are associated with subsequent decreases in cerebellar volume and, conversely, whether primary cerebellar injury is associated with decreased cerebral brain volumes, with advanced, 3-dimensional, volumetric MRI at term gestational age equivalent. METHODS: Total cerebellar volumes and cerebellar gray and myelinated white matter volumes were determined through manual outlining for 74 preterm infants with unilateral periventricular hemorrhagic infarction (14 infants), bilateral diffuse periventricular leukomalacia (20 infants), cerebellar hemorrhage (10 infants), or normal term gestational age equivalent MRI findings (30 infants). Total brain and right/left cerebral and cerebellar hemispheric volumes were calculated. RESULTS: Unilateral cerebral brain injury was associated with significantly decreased volume of the contralateral cerebellar hemisphere. Conversely, unilateral primary cerebellar injury was associated with a contralateral decrease in supratentorial brain volume. Cerebellar gray matter and myelinated white matter volumes were reduced significantly not only among preterm infants with primary cerebellar hemorrhage but also among infants with cerebral parenchymal brain injury. CONCLUSIONS: These data suggest strongly that both reduction in contralateral cerebellar volume with unilateral cerebral parenchymal injury and reduction in total cerebellar volume with bilateral cerebral lesions are related to trophic transsynaptic effects. Early-life cerebellar injury may contribute importantly to the high rates of cognitive, behavioral, and motor deficits reported for premature infants.

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.