扩散张量MR成像研究

本文一方面综述了8年来国际上扩散张量磁共振成像(DTI)的研究进展情况。包括总结了到目前为止所使用的4种提高DTI成像精度的方法，并指出精度的提高依赖于成像中脉冲序列的优化、实验方法的完善和后处理算法两个方面。文中比较了目前研究扩散张量的两种基本模型：扩散张量模型和q-空间模型。指出这两种模型侧重应用于不同的场合。前者侧重于研究器官或宏观组织中的扩散，而后者侧重于研究小到细胞尺度(μm量级)的扩散行为。两者在应用研究方面是互补的，所要求的实验条件是有差别的。另一方面结合文献对扩散张量模型的实验条件进行了理论分析。认为b因子取得过高并不合理。并用DTI实验数据和结果进行了初步验证。为了改进扩散张量模型本文探讨了考虑多指数衰减的设想。文中综述了DTI的导出量和一些实验结果，在此基础上分析了设计和优化各向异性指标(DAI)的原则。对于DTI的重要导出结果神经纤维柬成像(fiber tractography)重点分析了造成其成像精度不高的主要因素，指出了改进纤维束传导方向甄选算法和寻求纤维束方向场的几何性质是两种可能的解决办法。     

Two-step anomalous diffusion tensor imaging

We extend the formalism of anomalous diffusion imaging to include directional anisotropy of fitted parameters. The resulting technique is termed anomalous diffusion tensor imaging (aDTI), and allows the directional properties of the distributed diffusion coefficient (α) and the anomalous diffusion exponent, (γ) to be analysed using the same analytical techniques as regular diffusion tensor imaging (DTI). Together, these parameters quantify the rate of diffusion (α) and the complexity of the diffusion environment (γ). We generated tensor images for the anomalous exponent tensor (Γ) and distributed diffusivity tensor (A) from in vivo human brain data and present images of eigenvalues, eigenvectors, Trace/3 (Tr), fractional anisotropy (FA) and tensor shape measures. In white matter, A is found to have a median Tr = 0.56 × 10^{? 3}mm²s^{? 1}, FA = 0.58 and Γ Tr = 0.69, FA = 0.13. We observed that white matter shows a similar anisotropic geometry for the distributed diffusion tensor as for the regular diffusion tensor, whereas the anomalous exponent tensor exhibits a different shape characteristic which may be informative of tissue microstructure. Copyright © 2011 John Wiley & Sons, Ltd.     

A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease

In vivo diffusion tensor imaging (DTI) was performed on the quinolinic acid (QUIN) rat model of Huntington's disease, together with behavioral assessment of motor deficits and histopathological characterization. DTI and histology revealed the presence of a cortical lesion in 53% of the QUIN animals (QUIN^+ctx). Histologically, QUIN^+ctx were distinguished from QUIN^−ctx animals by increased astroglial reaction within a subregion of the caudate putamen and loss of white matter in the external capsula. Although both techniques are complementary, the quantitative character of DTI makes it possible to pick up subtle differences in tissue microstructure that are not identified with histology. DTI demonstrated differential changes of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the internal and external capsula, and within a subregion of the caudate putamen. It was suggested that FA increased due to a selective loss of the subcortical connections targeted by degenerative processes at the early stage of the disease, which might turn the striatum into a seemingly more organized structure. When tissue degeneration becomes more severe, FA decreased while AD, RD and MD increased.     

Comparison of interpolation methods of predominant cardiomyocyte orientation from in vivo and ex vivo cardiac diffusion tensor imaging data

Cardiac electrophysiology and cardiac mechanics both depend on the average cardiomyocyte long-axis orientation. In the realm of personalized medicine, knowledge of the patient-specific changes in cardiac microstructure plays a crucial role. Patient-specific computational modelling has emerged as a tool to better understand disease progression. In vivo cardiac diffusion tensor imaging (cDTI) is a vital tool to non-destructively measure the average cardiomyocyte long-axis orientation in the heart. However, cDTI suffers from long scan times, rendering volumetric, high-resolution acquisitions challenging. Consequently, interpolation techniques are needed to populate bio-mechanical models with patient-specific average cardiomyocyte long-axis orientations. In this work, we compare five interpolation techniques applied to in vivo and ex vivo porcine input data. We compare two tensor interpolation approaches, one rule-based approximation, and two data-driven, low-rank models. We demonstrate the advantage of tensor interpolation techniques, resulting in lower interpolation errors than do low-rank models and rule-based methods adapted to cDTI data. In an ex vivo comparison, we study the influence of three imaging parameters that can be traded off against acquisition time: in-plane resolution, signal to noise ratio, and number of acquired short-axis imaging slices.     

弥散张量成像在中枢神经系统中的应用

在磁共振成像(MRI)研究中,弥散张量成像(DTI)是最近几年提出并迅速发展的一个研究方向,本文介绍了弥散张量成像的原理以及国际上主要的研究热点,并结合实际介绍了弥散张量成像在中枢神经系统(CNS)中的应用。     

A meta-analysis of diffusion tensor imaging studies in amyotrophic lateral sclerosis

Studies involving diffusion tensor imaging (DTI) of amyotrophic lateral sclerosis (ALS) with whole-brain voxel-based analysis yielded variable findings. A systematic review was conducted on whole-brain voxel-based diffusion tensor imaging fractional anisotropy (FA) studies of ALS patients and healthy controls (HC) in PubMed, ISI Web of Science, Embase, and MEDLINE databases from 1990 to December 25, 2010. Coordinates were extracted from clusters with significant difference in FA between ALS patients and HC. Meta-analysis was performed using signed differential mapping. Eight studies were enrolled, comprising 143 ALS patients and 145 HC. The included studies reported FA reduction at 67 coordinates in ALS and no FA increased. Significant reductions were present in the bilateral frontal white matter/cingulate gyrus and the posterior limb of bilateral internal capsule. The findings remain largely unchanged in quartile and jackknife sensitivity analyses. Our finding suggests that ALS is a multisystem disease beyond motor dysfunction and provides evidence that FA reduction in the frontal white matter and cingulate gyrus may be a special biomarker of ALS.     

Longitudinal diffusion tensor imaging in a rat brain glioma model

In order to investigate the properties of water motion within and around brain tumors as a function of tumor growth, longitudinal diffusion tensor imaging (DTI) was carried out in a rat brain glioma (C6) model. As tumors grew in size, significant anisotropy of water diffusion was seen both within and around the tumor. The tissue water surrounding the tumor exhibited high planar anisotropy, as opposed to the linear anisotropy normally seen in white matter, indicating that cells were experiencing stress in a direction normal to the tumor border. When tumors were sufficiently large, significant anisotropy was also seen within the tumor because of longer-range organization of cancer cells within the tumor borders. These findings have important implications for diffusion-weighted MRI experiments examining tumor growth and response to therapy. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Diffusion tensor imaging and mild parkinsonian signs in cerebral small vessel disease

Although the role of cerebral small vessel disease (SVD), including white matter lesions (WMLs) and lacunar infarcts, in mild parkinsonian signs (MPS) is increasingly being recognized, not all individuals with SVD have MPS. Using diffusion tensor imaging (DTI), we investigated whether the presence of MPS was dependent on the microstructural integrity underlying WMLs, the early loss of integrity of the normal-appearing white matter (NAWM) and location of this damage. We examined 483 elderly subjects with SVD and without parkinsonism. Subjects with severe loss of integrity within their WMLs had a higher risk of MPS, regardless of WML volume (fractional anisotropy odds ratios = 1.9; 95% confidence interval, 1.1-3.4). The same was found in the normal-appearing white matter, but this association disappeared after adjustment for WMLs and lacunar infarcts. The integrity of the periventricular frontal regions-of-interest was significantly lower in subjects with MPS than without, independent of WMLs and lacunar infarcts. This study indicates that integrity of WMLs, especially in the frontal lobe, is associated with MPS. Diffusion tensor imaging may be of added value in investigating the underlying mechanisms of parkinsonian signs in subjects with SVD.     

A diffusion tensor imaging analysis of gender differences in water diffusivity within human skeletal muscle

The diffusive properties of adjacent muscles at rest were evaluated in male (n = 12) and female (n = 12) subjects using diffusion tensor imaging (DTI). The principle, second and third eigenvalues, trace of the diffusion tensor [Tr(D)], and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated from the diffusion tensor. Seven muscles were investigated in this study from images acquired of the left calf: the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus and peroneus longus. A mathematical model was also derived that relates the eigenvalues of the diffusion tensor to the muscle fiber volume fraction, which is defined as the volume of muscle fibers within a well-defined arbitrary muscle volume. Females on average had higher eigenvalues and Tr(D) compared with males, with the majority of muscles being statistically different between the sexes. In contrast, males on average had higher e and FA than females, with the large plantar flexors--soleus, lateral gastrocnemius, and medial gastrocnemius--producing statistically different results. The behavior of the mathematical model for variations in fiber volume fraction produced similar trends to those seen when the experimental data were fit to the model. The model predicts that a larger volume fraction of skeletal muscle in males is devoted to fibers than in females, but the true underlying source of the gender discrepancy remains unclear. Although the model does not fully account for other transport processes, it does provide some insight into the limiting factors that affect the diffusion of water in skeletal muscle measured by DTI.     

Considerations in high-resolution skeletal muscle diffusion tensor imaging using single-shot echo planar imaging with stimulated-echo preparation and sensitivity encoding

Previous studies have shown that skeletal muscle diffusion tensor imaging (DTI) can noninvasively probe changes in the muscle fiber architecture and microstructure in diseased and damaged muscles. However, DTI fiber reconstruction in small muscles and in muscle regions close to aponeuroses and tendons remains challenging because of partial volume effects. Increasing the spatial resolution of skeletal muscle single-shot diffusion-weighted echo planar imaging (DW-EPI) can be hindered by the inherently low signal-to-noise ratio (SNR) of muscle DW-EPI because of the short muscle T(2) and the high sensitivity of single-shot EPI to off-resonance effects and T(2)* blurring. In this article, eddy current-compensated diffusion-weighted stimulated-echo preparation is combined with sensitivity encoding (SENSE) to maintain good SNR properties and to reduce the sensitivity to distortions and T(2)* blurring in high-resolution skeletal muscle single-shot DW-EPI. An analytical framework is developed to optimize the reduction factor and diffusion weighting time to achieve maximum SNR. Arguments for the selection of the experimental parameters are then presented considering the compromise between SNR, B(0)-induced distortions, T(2)* blurring effects and tissue incoherent motion effects. On the basis of the selected parameters in a high-resolution skeletal muscle single-shot DW-EPI protocol, imaging protocols at lower acquisition matrix sizes are defined with matched bandwidth in the phase-encoding direction and SNR. In vivo results show that high-resolution skeletal muscle DTI with minimized sensitivity to geometric distortions and T(2)* blurring is feasible using the proposed methodology. In particular, a significant benefit is demonstrated from a reduction in partial volume effects for resolving multi-pennate muscles and muscles with small cross-sections in calf muscle DTI.     

Microarchitecture of the hearts in term and former-preterm lambs using diffusion tensor imaging

Diffusion tensor imaging (DTI) is an MRI technique that can be used to map cardiomyocyte tracts and estimate local cardiomyocyte and sheetlet orientation within the heart. DTI measures diffusion distances of water molecules within the myocardium, where water diffusion generally occurs more freely along the long axis of cardiomyocytes and within the extracellular matrix, but is restricted by cell membranes such that transverse diffusion is limited. DTI can be undertaken in fixed hearts and it allows the three-dimensional mapping of the cardiac microarchitecture, including cardiomyocyte organization, within the whole heart. The objective of this study was to use DTI to compare the cardiac microarchitecture and cardiomyocyte organization in archived fixed left ventricles of lambs that were born either preterm (n = 5) or at term (n = 7), at a postnatal timepoint equivalent to about 6 years of age in children. Although the findings support the feasibility of retrospective DTI scanning of fixed hearts, several hearts were excluded from DTI analysis because of poor scan quality, such as ghosting artifacts. The preliminary findings from viable DTI scans (n = 3/group) suggest that the extracellular compartment is altered and that there is an immature microstructural phenotype early in postnatal life in the LV of lambs born preterm. Our findings support a potential time-efficient imaging role for DTI in detecting abnormal changes in the microstructure of fixed hearts of former-preterm neonates, although further investigation into factors that affect scan quality is required.     

Association between sociability and diffusion tensor imaging in BALB/cJ mice

The purpose of this study was to use high-resolution diffusion tensor imaging (DTI) to investigate the association between DTI metrics and sociability in BALB/c inbred mice. The sociability of prepubescent (30-day-old) BALB/cJ mice was operationally defined as the time that the mice spent sniffing a stimulus mouse in a social choice test. High-resolution ex vivo DTI data on 12 BALB/cJ mouse brains were acquired using a 9.4-T vertical-bore magnet. Regression analysis was conducted to investigate the association between DTI metrics and sociability. Significant positive regression (p < 0.001) between social sniffing time and fractional anisotropy was found in 10 regions located in the thalamic nuclei, zona incerta/substantia nigra, visual/orbital/somatosensory cortices and entorhinal cortex. In addition, significant negative regression (p < 0.001) between social sniffing time and mean diffusivity was found in five areas located in the sensory cortex, motor cortex, external capsule and amygdaloid region. In all regions showing significant regression with either the mean diffusivity or fractional anisotropy, the tertiary eigenvalue correlated negatively with the social sniffing time. This study demonstrates the feasibility of using DTI to detect brain regions associated with sociability in a mouse model system.     

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time‐consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi‐automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post‐marathon and follow‐up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi‐automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out‐of‐phase Dixon images at baseline. These segmentations were longitudinally propagated for the post‐marathon and follow‐up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi‐automatic segmentations. Bland‐Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ₃). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland‐Altman analysis showed that the 95% limits of agreement for MD, FA and λ₃ ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA and λ₃ (r = 0.99, p < 60; 0.0001). In conclusion, the supervised semi‐automatic segmentation framework successfully quantified DTI indices in the upper‐leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.     

A review of diffusion tensor magnetic resonance imaging computational methods and software tools

In this work we provide an up-to-date short review of computational magnetic resonance imaging (MRI) and software tools that are widely used to process and analyze diffusion-weighted MRI data. A review of different methods used to acquire, model and analyze diffusion-weighted imaging data (DWI) is first provided with focus on diffusion tensor imaging (DTI). The major preprocessing, processing and post-processing procedures applied to DTI data are discussed. A list of freely available software packages to analyze diffusion MRI data is also provided.     

Effects of pioglitazone on diffusion tensor imaging indices in multiple sclerosis patients

Pioglitazone is an FDA-approved peroxisome proliferator activated receptor gamma (PPARγ) agonist. We tested the hypothesis that treatment with pioglitazone reduces new lesion development in patients with RRMS. Twenty-two patients were treated with pioglitazone or placebo and monitored by diffusion tensor imaging (DTI) at baseline and after 12 months. A negative correlation was found between the 1-year change in relative anisotropy (RA) and fluid attenuated inversion recovery (FLAIR) lesion burden in the pioglitazone group. Regions of interest (ROIs) having high ADC and low RA values at baseline had a significantly higher chance to develop into lesions in the placebo group than similar ROIs in the pioglitazone group. These findings suggest that baseline DTI parameters can provide a prognostic surrogate marker for lesions, and that pioglitazone can reduce conversion of normal appearing white matter to lesions.     

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation

Non‐invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end‐stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end‐stage heart failure as a result of idiopathic dilated cardiomyopathy (n = 14) and from normal donors (n = 5). Scalar DTI parameters, including fractional anisotropy (FA) and mean (MD), primary (D₁), secondary (D₂) and tertiary (D₃) diffusivities, were correlated with collagen content measured by digital microscopy. Compared with hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D₂ and D₃ increased by 12%, 14% and 24%, respectively (P < 0.01). No significant change was detected for D₁ between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e. fibrosis). Pearson's correlation coefficients (r) between collagen content and FA, MD, D₂ and D₃ were –0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D₁ and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for the non‐invasive assessment of diffuse fibrosis in failing hearts. Copyright © 2014 John Wiley & Sons, Ltd.     

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel‐based analysis are highly dependent on the user‐hypothesis and parameter settings for implementation. In contrast, tract‐based spatial statistics (TBSS) allows for reliable voxel‐wise analysis via the projection of diffusion‐derived parameters onto an alignment‐invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI‐derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2–4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post‐stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post‐stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo‐normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.     

Cardiovascular effects of noise during complex task performance

Ten human subjects were stimulated with intermittent pink noise during the performance of a computerized task. Each subject received 3 consecutive sessions consisting of 10 min of baseline, 30 min of task performance, and 10 min of post-task baseline. Noise stimulation was presented during minutes 10-20 of task performance. Task performance was associated with significant increases in mean blood pressure, heart rate, and respiration rate and significant decreases in digital pulse amplitude. Noise stimulation was associated with a further decrease in digital pulse amplitude and a further increase in mean blood pressure. Noise- and task-elicited blood pressure and vasomotor responses did not habituate.     

Regional variation in lateral and medial gastrocnemius muscle fibre lengths obtained from diffusion tensor imaging

Assessment of regional muscle architecture is primarily done through the study of animals, human cadavers, or using b-mode ultrasound imaging. However, there remain several limitations to how well such measurements represent in vivo human whole muscle architecture. In this study, we developed an approach using diffusion tensor imaging and magnetic resonance imaging to quantify muscle fibre lengths in different muscle regions along a muscle's length and width. We first tested the between-day reliability of regional measurements of fibre lengths in the medial (MG) and lateral gastrocnemius (LG) and found good reliability for these measurements (intraclass correlation coefficient [ICC] = 0.79 and ICC = 0.84, respectively). We then applied this approach to a group of 32 participants including males (n = 18), females (n = 14), young (24 ± 4 years) and older (70 ± 2 years) adults. We assessed the differences in regional muscle fibre lengths between different muscle regions and between individuals. Additionally, we compared regional muscle fibre lengths between sexes, age groups, and muscles. We found substantial variability in fibre lengths between different regions within the same muscle and between the MG and the LG across individuals. At the group level, we found no difference in mean muscle fibre length between males and females, nor between young and older adults, or between the MG and the LG. The high variability in muscle fibre lengths between different regions within the same muscle, possibly expands the functional versatility of the muscle for different task requirements. The high variability between individuals supports the use of subject-specific measurements of muscle fibre lengths when evaluating muscle function.     

Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.