Reduced anisotropy of water diffusion in structural cerebral abnormalities demonstrated with diffusion tensor imaging

We used diffusion tensor imaging (DTI) to investigate the behavior of water diffusion in cerebral structural abnormalities. The fractional anisotropy, a measure of directionality of the molecular motion of water, and the mean diffusivity, a measure of the magnitude of the molecular motion of water, were measured in 18 patients with longstanding partial epilepsy and structural abnormalities on standard magnetic resonance imaging and the results compared with measurements in the white matter of 10 control subjects. Structural abnormalities were brain damage (postsurgical brain damage, nonspecific brain damage, perinatal brain damage, perinatal infarct, ischemic infarct, perinatal hypoxia, traumatic brain damage (n = 3), mitochondrial cytopathy and mesiotemporal sclerosis), dysgenesis (cortical dysplasia (n = 2) and heterotopia) and tumors (meningioma (n = 2), hypothalamic hamartoma and glioma). Anisotropy was reduced in all structural abnormalities. In the majority of abnormalities this was associated with an increased mean diffusivity; however, 30% of all structural abnormalities (some patients with brain damage and dysgenesis) had a normal mean diffusivity in combination with a reduced anisotropy. There was no correlation between fractional anisotropy and mean diffusivity measurements in structural abnormalities (r = -0.1). Our findings suggest that DTI is sensitive for the detection of a variety of structural abnormalities, that a reduced anisotropy is the common denominator in structural cerebral abnormalities of different etiologies and that mean diffusivity and fractional anisotropy may be, in part, independent. Combined measurements of mean diffusivity and fractional anisotropy are likely to increase the specificity of DTI.     

A study of rotationally invariant and symmetric indices of diffusion anisotropy.

This study investigated the properties of a class of rotationally invariant and symmetric (relative to the principal diffusivities) indices of the anisotropy of water self-diffusion, namely fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR), with particular emphasis to their measurement in brain tissues. A simplified theoretical analysis predicted significant differences in the sensitivities of the anisotropy indices (AI) over the distribution of the principal diffusivities. Computer simulations were used to investigate the effects on AI image quality of three magnetic resonance (MR) diffusion tensor imaging (DTI) acquisition schemes, one being novel: the schemes were simulated on cerebral model fibres varying in shape and spatial orientation. The theoretical predictions and the results of the simulations were corroborated by experimentally determined spatial maps of the AI in a normal feline brain in vivo. We found that FA mapped diffusion anisotropy with the greatest detail and SNR whereas VR provided the strongest contrast between low- and high-anisotropy areas at the expense of increased noise contamination and decreased resolution in anisotropic regions. RA proved intermediate in quality. By sampling the space of the effective diffusion ellipsoid more densely and uniformly and requiring the same total imaging time as the published schemes, the novel DTI scheme achieved greater rotational invariance than the published schemes, with improved noise characteristics, resulting in improved image quality of the AI examined. Our findings suggest that significant improvements in diffusion anisotropy mapping are possible and provide criteria for the selection of the most appropriate AI for a particular application.     

Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI.

We used diffusion tensor imaging to assess diffusion anisotropy in the pyramidal tract in ten young, and ten elderly subjects (five males and five females in each group). The purpose of this study was to define normative values for anisotropy at different anatomic levels of the brainstem as well as to assess differences due to age, gender, and laterality. In all subjects, anisotropy was highest in the cerebral peduncle, lowest in the caudal pons, and intermediate in the medulla. In the pons and medulla the regional variability was high, with significant differences in anisotropy even between contiguous slices. Multifactorial ANOVA (performed using the average value of anisotropy within each region of interest) revealed that elderly subjects had significantly lower values than young subjects in the cerebral peduncle, with no differences in the pons and medulla. No significant differences in anisotropy due to gender and side were found. The differences in anisotropy at different levels of the brainstem reflect differences in the local architecture of white matter fibers. Anisotropy is high in the cerebral peduncle because fibers have a highly ordered arrangement, while in the pons and medulla, anisotropy is lower because the local fiber architecture is less coherent due to the presence of other fibers and nuclei. The biologic meaning of the intergroup differences in anisotropy is discussed in light of the structure and architecture of the tissue under investigation. We also consider potential sources of artifacts, such as noise and motion, partial volume contamination, anatomic mismatching, and the use of inappropriate statistical tests. We conclude that the age-related decrease in anisotropy in the cerebral peduncle is not artifactual but rather reflects subtle structural changes of the aging white matter. Our study however shows that caution must be exercised in interpreting diffusion anisotropy data.     

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).     

Water diffusion features as indicators of muscle structure ex vivo

The structures of two different bovine muscles, the Semitendinosus (ST) and the Triceps brachii (TB), were studied using quantitative maps obtained by diffusion tensor imaging at 4.7 T. The estimated features were: mean diffusivity, intra- and inter-voxel anisotropy and fiber tract orientation angles. Significant differences in anisotropy (fractional anisotropy and lattice index), spatial variations of anisotropy and fiber tract orientation were detected between ST and TB, and are discussed. Accumulation of free water, which diffuses more freely and isotropically than in the rest of the muscle, was detected and localized in ST. These results underline the usefulness of diffusion tensor measurements to characterize muscle structure and help understand the mechanisms of post mortem water exudation.     

Diffusion tensor MRI in temporal lobe epilepsy

The purpose of this study was to investigate the diffusion characteristics of white matter in patients with focal temporal lobe epilepsy (TLE). Diffusion tensor imaging (DTI) was applied to patients and normal controls. Rotationally invariant mean diffusivity and diffusion anisotropy maps were calculated for all subjects. Comparisons between the two groups were performed for several white matter structures. Mean diffusivity and diffusion anisotropy of each selected structure were tested for correlations with age at onset and duration of epilepsy. Significantly lower diffusion anisotropy, and higher diffusivity in directions perpendicular to the axons, was detected in several white matter structures of the patients when compared to the controls. These structures were not located in the temporal lobes. No significant difference in mean diffusivity was detected between the selected structures from the two groups. Diffusion anisotropy was significantly correlated with age at onset of epilepsy in the posterior corpus callosum. Duration of epilepsy was not significantly correlated with the diffusion indices from any of the selected structures. The results of this study suggest that diffusion anisotropy may reveal abnormalities in patients with focal TLE. In addition, these abnormal changes are not necessarily restricted to the temporal lobes but might extend in other brain regions as well. Furthermore, the age at onset of epilepsy may be an important factor in determining the extent of the effect of epilepsy on white matter.     

Investigation of techniques to quantify in vivo lesion volume based on comparison of water apparent diffusion coefficient (ADC) maps with histology in focal cerebral ischemia of rats

Stroke lesion-volume estimates derived from calculated water apparent diffusion coefficient (ADC) maps provide a quantitative surrogate end-point for investigating the efficacy of drug treatment or studying the temporal evolution of cerebral ischemia. Methodology is described for estimating ischemic lesion volumes in a rat model of permanent middle cerebral artery occlusion (MCAO) based on absolute and percent-reduction threshold values of the water ADC at 3 h post-MCAO. Volume estimates derived from average ADC (ADC(av)) maps were compared with those derived from post-mortem histological sections. Optimum ADC thresholds were established as those that provided the best correlation and one-to-one correspondence between ADC- and histologically derived lesion-volume estimates. At 3 h post-MCAO, an absolute-ADC(av) threshold of 47 x 10(-5) mm(2)/s (corresponding to a 33% reduction in ADC(av) based on a contralateral hemisphere comparison) provided the most accurate estimate of percent hemispheric lesion volume (%HLV). Experimental and data analysis issues for improving and validating the usefulness of DWI as a surrogate endpoint for the quantification of ischemic lesion volume are discussed.     

描述人体内水分子扩散各向异性特征的新方法

通过核磁共振扩散张量成像(DTI)得到的特定值域的扩散各向异性指数(DAI) 可用于揭示水分子扩散椭球的形态学特征, 定量反映被成像物体内部水分子扩散的优势方向和强度, 间接得到被成像物体内部的组织结构信息. DAI的可靠性直接影响对DTI数据的分析和理解. 本文基于扩散张量椭球的几何学信息, 提出利用扩散椭球几何比(EGR)定量描述水分子扩散的各向异性程度. 通过蒙特卡罗模拟实验和对人脑DTI数据进行分析, 并与当前广泛应用的水分子扩散各向异性分数(FA)和近期文献提出的扩散椭球面积比(EAR)进行对比. 实验发现EGR在不同级别噪声影响下的对比度效果和抗噪性都优于FA及EAR. 而且EGR 加入了体积修正, 增强了盘形扩散张量情况下的敏感性, 能够更好地鉴别神经纤维束交叉情况, 对于各向异性扩散程度较高的白质深层和相对均质的表层都有较好的量化区分结果. 关键词： 扩散系数 各向异性扩散 扩散张量成像 扩散椭球几何比     

Aging effects on cerebral asymmetry: a voxel-based morphometry and diffusion tensor imaging study

The hemispheres of the human brain are functionally and structurally asymmetric. The purpose of this study was to evaluate the effects of aging on gray and white matter asymmetry. Two hundred twenty-six right-handed normal volunteers aged 21–71 years were included in this study. The effects of aging on gray matter volume asymmetry and white matter fractional anisotropy asymmetry were evaluated with use of voxel-based morphometry and voxel-based analysis of fractional anisotropy maps derived from diffusion tensor imaging (DTI), respectively. The voxel-based morphometry showed no significant correlation between age and gray matter volume asymmetry. The voxel-based analysis of DTI also showed no significant correlation between age and white matter fractional anisotropy asymmetry. Our results showed no significant effects of aging on either gray matter volume asymmetry or white matter fractional anisotropy asymmetry.     

Intermolecular double quantum coherences (iDQc) and diffusion-weighted imaging (DWI) imaging of the human brain at 1.5 T

To study the sensitivity of intermolecular double quantum coherences (iDQc) imaging contrast to brain microstructure and brain anisotropy, we investigated the iDQC contrast between differently structured areas of the brain according to the strength and the direction of the applied correlation gradient. Thus diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) maps have been obtained. This procedure, which consists of analyzing both iDQc and DWI images at different gradient strength and gradient direction, could be a promising tool for clinical brain investigations performed with higher than 1.5 T magnetic fields.     

Study of pediatric brain development using magnetic resonance imaging of anisotropic diffusion

The properties of water diffusion in human brain tissue can be characterized by diffusion tensors computed from diffusion weighted magnetic resonance images. Since these properties are strongly determined by the structural and geometrical characteristics of the tissue, the maturation process of white matter and gray matter tissue can be expected to be reflected in these images and derived tensor quantities. The purpose of this work was therefore to study the development of pediatric brain in terms of changes occurring in the observed diffusion behavior. Echo planar diffusion tensor imaging was performed on 22 (10 females and 12 males) full term newborn and infant patients, diagnosed in retrospect as neurologically healthy. The subjects were subdivided in three age categories. A number of quantities based on the diffusion images were calculated for each tissue type and age category, and the ability of these quantities to provide sensitive and consistent information about the tissue differences and evolution was evaluated. The results clearly illustrate that the rotationally invariant quantities (e.g., the highest diffusivity, anisotropy ratio and volume ratio) are superior to the rotationally variant ones (e.g., ADCs measured along the three axes of the magnet) often used in the clinic. On the basis of the anisotropy ratio and the volume ratio indices, a correlation between the white matter maturation and the evolution of the diffusion anisotropy could be established. The same quantities did not exhibit any age dependence for the gray matter tissues.     

灵长类中风模型的磁共振成像

灵长类大脑在结构、生理、功能及神经学上与人类大脑非常相似. 因此,灵长类中风模型为研究大脑缺血的损伤机制和开发各种药物治疗方法提供了理想的动物模型. 该文介绍了近年来使用的各种灵长类中风模型,并总结了目前可用于该模型的各种磁共振成像（MRI）方法. 同时,还讨论了灵长类动物高分辩弥散张量成像（DTI）和磁共振灌注成像（PWI）的数据采集方法和心跳及呼吸引起的生理运动伪影的矫正方法. 这些方法改进了弥散一灌注失配（DWI－PWI MISMATCH）成像的精度和质量,有助于提高对脑缺血半暗带演化及其对药物治疗反应的精确评估,为更好地利用灵长类脑中风模型和当代磁共振成像技术进行中风机制研究和药物开发建立一个理想的研究平台.     

Deconvolution with simple extrapolation for improved cerebral blood flow measurement in dynamic susceptibility contrast magnetic resonance imaging during acute ischemic stroke

Magnetic resonance (MR) perfusion imaging is a clinical technique for measuring brain blood flow parameters during stroke and other ischemic events. Ischemia in brain tissue can be difficult to accurately measure or visualize when using MR-derived cerebral blood flow (CBF) maps. The deconvolution techniques used to estimate flow can introduce a mean transit time-dependent bias following application of noise stabilization techniques. The underestimation of the CBF values, greatest in normal tissues, causes a decrease in the image contrast observed in CBF maps between normally perfused and ischemic tissues; resulting in ischemic areas becoming less conspicuous. Through application of the proposed simple extrapolation technique, CBF biases are reduced when missing high-frequency signal components in the MR data removed during deconvolution noise stabilization are restored. The extrapolation approach was compared with other methods and showed a statistically significant increase in image contrast in CBF maps between normal and ischemic tissues for white matter (P<.05) and performed better than most other methods for gray matter. Receiver operator characteristic curve analysis demonstrated that extrapolated CBF maps better-detected penumbral regions. Extrapolated CBF maps provided more accurate CBF estimates in simulations, suggesting that the approach may provide a better prediction of outcome in the absence of treatment.     

Understanding changes in DTI metrics in patients with different stages of neurocysticercosis

Diffusion tensor imaging (DTI) was performed on 25 patients with neurocysticercosis (NCC). The aim of this study was to investigate the changes in DTI measures during the evolutionary course of NCC lesions from vesicular to calcified stage in the brain. DTI measures were quantified from the NCC lesions of all patients. On the basis of conventional imaging findings, NCC lesions were classified into vesicular, vesicular colloidal, granular nodular and calcified stages. Significant inverse correlation was observed between the evolutionary stage of NCC lesion and mean diffusivity (MD; r=−0.748, P<0.001) and spherical anisotropy (CS; r=−0.585, P<.001) values. Significant direct correlations were observed between evolutionary stages of NCC lesion and mean fractional anisotropy (FA; r=0.575, P<0.001), linear anisotropy (CL; r=0.478, p<0.001) and planar anisotropy (CP; r=0.561, p<0.001) values. Successive decrease in MD values calculated from NCC lesions was observed, moving from vesicular to granular nodular stage. On FA, CL and CP maps, a significant increase in signal intensity value was observed in calcified as compared to other stages. We conclude that DTI measures may indicate the evolutionary changes in NCC from vesicular to calcified stage.     

In vivo visualization of displacement-distribution-derived parameters in q-space imaging

OBJECTIVE: This study aimed to explore the potential of in vivo q-space imaging in the differentiation between different cerebral water components. MATERIALS AND METHODS: Diffusion-weighted imaging was performed in six directions with 32 equally spaced q values and a maximum b value of 6600 s/mm(2). The shape of the signal-attenuation curve and the displacement propagator were examined and compared with a normal distribution using the kurtosis parameter. Maps displaying kurtosis, fast and slow components of the apparent diffusion coefficients, fractional anisotropy and directional diffusion were calculated. The displacement propagator was further described by the full width at half and at tenth maximum and by the probability density of zero displacement P(0). Three healthy volunteers and three patients with previously diagnosed multiple sclerosis (MS) were examined. RESULTS: Simulations indicated that the kurtosis of a signal-attenuation curve can determine if more than one water component is present and that care must be taken to select an appropriate threshold. It was possible to distinguish MS plaques in both signal and diffusional kurtosis maps, and in one patient, plaques of different degree of demyelinization showed different behavior. DISCUSSION: Our results indicate that in vivo q-space analysis is a potential tool for the assessment of different cerebral water components, and it might extend the diagnostic interpretation of data from diffusion magnetic resonance imaging.     

Diffusion changes in patients with systemic lupus erythematosus

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE. METHODS: Data from 34 SLE patients (age range, 18-73 years) and 29 age-matched volunteers (age range, 29-64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (D(av)) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BD(av)). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant. RESULTS: Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BD(av) and D(av) values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BD(av) and D(av) values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the D(av) values of the thalamus between the SLE patients and the control subjects. The BD(av) value in the SLE patient group was robustly correlated with the D(av) values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of D(av) and FA values in the SLE patient group. CONCLUSION: Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BD(av) and D(av) values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.     

Computational modeling of cerebral diffusion-application to stroke imaging

Water diffusion within the structure of a brain extracellular space is analyzed numerically for various diffusion parameters of brain tissue namely extracellular space porosity and tortuosity. An algorithm for predicting diffusion pattern of water molecules within human brain considering the mechanics of water diffusion within porous media is developed. The extracellular space is modeled as a homogeneous porous medium with uniform porosity and permeability. Discretization of the fluid flow, heat transfer and mass transport equations is achieved using a finite element scheme based on the Galerkin method of weighted residuals. Concentration maps are developed in this study for various clinical conditions. The effect of the space porosity and the turtousity on the heat and mass transport within the extracellular space are found to be significant. The results presented in this work play an important role in producing more effective imaging techniques for brain injury based on the apparent diffusion coefficient.     

Keyhole and zero-padding approaches for reduced-encoding diffusion tensor imaging of the mouse brains

Keyhole diffusion tensor imaging (keyhole DTI) was previously proposed in cardiac imaging to reconstruct DTI maps from the reduced phase-encoding images. To evaluate the feasibility of keyhole DTI in brain imaging, keyhole and zero-padding DTI algorithms were employed on in vivo mouse brain. The reduced phase-encoding portion, also termed as the sharing rate, was varied from 50% to 90% of the full k-space. Our data showed that zero-padding DTI resulted in decreased fractional anisotropy (FA) and decreased mean apparent diffusion coefficient (mean ADC) in white matter (WM) regions. Keyhole DTI showed a better edge preservation on mean ADC maps but not on FA maps as compared to the zero-padding DTI. When increasing the sharing rate in keyhole approach, an underestimation of FA and an over- or underestimation of mean ADC were measured in WM depending on the selected reference image. The inconsistency of keyhole DTI may add a challenge for the wide use of this modality. However, with a carefully selected directive diffusion-weighted image to serve as the reference image in the keyhole approach, this study demonstrated that one may obtain DTI indices of reduced-encoding images with high consistency to those derived with full k-space DTI.     

Correction of eddy current-induced artefacts in diffusion tensor imaging using iterative cross-correlation.

Geometric distortions of echo-planar images produced by the strong eddy currents present in the diffusion tensor imaging experiment are a major confound to the accurate quantification of diffusion coefficients, and measures of diffusion anisotropy based upon them. Here we investigate how the method of iterative cross-correlation (ICC) of baseline and diffusion-weighted images (DWIs) originally proposed by Haselgrove and Moore (Magn. Reson. Med. 36:960-964; 1996) can be extended to correct high b-value DWIs, without the need for extrapolation of distortion parameters determined from low b-value images. Monte Carlo simulations of synthetic brain images show that the maximum value of the trace of the b-matrix, Tr(b), at which distorted DWIs can be accurately corrected by direct comparison with the undistorted baseline image is approximately 300 s mm(-2). Removal of the cerebrospinal fluid signal greatly extends this value of Tr(b) (up to approximately 2000 s mm(-2)), thereby allowing direct comparison of baseline and distorted images. The use of ICC distortion parameters determined from separate calibrations of water phantom images is also investigated, and found to be effective in correcting geometric distortions observed in the DWIs collected as part of a human volunteer diffusion tensor imaging study. This work suggests that distorted DWIs acquired at high values of b may be corrected using the ICC algorithm without collecting additional low b-value images, thus allowing simplified methods of measuring the apparent diffusion tensor D, based on collecting a small number of DWIs, to be implemented in quantitative patient examinations.