Evaluation of voxel-based group-level analysis of diffusion tensor images using simulated brain lesions

We simulated brain lesions in mean diffusivity (MD) and fractional anisotropy (FA) images of healthy subjects to evaluate the performance of voxel-based analysis (VBA) with SPM2. We increased MD and decreased FA, simulating the most typical abnormalities in brain pathologies, in the superior longitudinal fasciculus (SLF), corticospinal tract (CST), and corpus callosum (CC). Lesion sizes varied from 10 to 400 voxels (10.5 mm³ each) and intensity changes from 10 to 100%. The VBA contained eddy current correction, spatial normalization, smoothing, and statistical analysis.The preprocessing steps changed the intensities of MD and FA lesions from the original values, and many lesions remained undetected. The detection thresholds varied between the three brain areas, and between MD and FA images. Although spatial smoothing often improved the sensitivity, it also markedly enlarged the estimated lesion sizes.Since conventional VBA preprocessing significantly affected the outcome and sensitivity of the method itself, the impact of analysis steps should be verified and considered before interpreting the findings. Our results provide insight into the sizes and intensity changes of lesions that can be detected with VBA applied to diffusion tensor imaging (DTI) data.     

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.     

Relationship between diffusion tensor imaging and brain morphology in patients with myotonic dystrophy

Myotonic dystrophy type 1 (MyD) is a common inherited neuromuscular disorder. In addition to neuromuscular symptoms, many MyD patients show central nervous system neuropathology. This study evaluated whether MyD patients display diffusion tensor (DT) abnormalities associated with regional cortical atrophy and clinical features. Three-dimensional T1-weighted and DT magnetic resonance images of the brain were obtained in 11 MyD patients and 13 age- and sex-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in corpus callosum subregions with DT imaging (DTI) along with volumetric changes, and correlations with clinical features were examined. Differences between MyD patients and healthy subjects were analyzed statistically. Significantly lower FA and higher MD values were found in the genu, rostral body, anterior midbody, posterior midbody and splenium in MyD patients than in control subjects (p < 0.05, corrected; lower FA in the splenium was at a trend level). These corpus callosum subregions were the areas connected to cortical areas where significantly lower volumes were found in MyD patients. No significant decrease in volumes was noted in the parietal cortex, where connecting fibers pass through the isthmus in which DTI abnormalities were not detected in MyD patients. Significant negative correlations to volumes of frontal areas were noted, particularly bilateral motor areas, with cytosine thymine guanidine (CTG) triplet expansion. DTI results in corpus callosum may reflect morphological changes in the connecting cortical areas of MyD patients.     

应用弥散张量成像技术检测慢性原发性闭角型青光眼患者脑白质结构

目的 采用磁共振弥散张量成像(DTI)检测慢性闭角型青光眼(PACG)患者脑白质病变,用各向异性指数(FA)改变分析病变部位。方法 回顾性分析2008-2009年在天津医科大学总医院眼科就诊并行颅脑MRI检查患者的临床资料,其中确诊为慢性PACG并同时行DTI扫描的患者25例为慢性PACG组,根据视野损害程度分为轻度组和重度组;选取同一时间段行颅脑DTI扫描的健康人25例为正常对照组。采用FSL和DTIstudio软件处理原始数据得到FA图,输入SPM5软件做标准化处理,然后进行灰白质分割,对分割后的白质FA图进行平滑处理,最后对慢性PACG组和正常对照组FA图进行两样本t检验比较,采用FWE方法校正统计结果,取P＜0.05有统计学意义,将结果叠加于标准模板,显示阈值设定为10个体素。采用同样方法分析慢性PACG轻度组和重度组FA图差异。结果剔除头动明显受试者图像后,慢性PACG组和正常对照组各有22例入组,慢性PACG组分为轻度组13例、重度组9例。与正常对照组比较,慢性PACG患者双侧视束脚周段FA值明显降低(P＜0.05,FWE校正),左侧包含98个体素,右侧包含56个体素。慢性PACG轻度组与重度组FA值差异无统计学意义(P＞0.05)。结论 DTI可检测慢性PACG患者脑白质结构病变。FA值可反应双侧视束脚周段病变。     

Structural brain alterations in bipolar disorder II: A combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study

Background

Brain structural changes have been described in bipolar disorder (BP), but usually studies focused on both I and II subtypes indiscriminately and investigated changes in either brain volume or white matter (WM) integrity. We used combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to track changes in the grey matter (GM) and WM in the brains of patients affected by BPII, as compared to healthy controls.

Methods

Using VBM and DTI, we scanned 20 DSM-IV-TR BPII patients in their euthymic phase and 21 healthy, age- and gender-matched volunteers with no psychiatric history.

Results

VBM showed decreases in GM of BPII patients, compared to controls, which were diffuse in nature and most prominent in the right middle frontal gyrus and in the right superior temporal gurus. DTI showed significant and widespread FA reduction in BPII patients in all major WM tracts, including cortico-cortical association tracts.

Limitations

The small sample size limits the generalisability of our findings.

Conclusions

Reduced GM volumes and WM integrity changes in BPII patients are not prominent like those previously reported in bipolar disorder type-I and involve cortical structures and their related association tracts.     

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.     

Effects of aging on the ventral and dorsal substantia nigra using diffusion tensor imaging

Dopaminergic neurons in the substantia nigra produce dopamine for the nigrostriatal pathway that facilitates motor function. Postmortem examinations demonstrate an age-related loss of cells in the substantia nigra, with most of the cell loss focused on the dorsal substantia nigra compared with the ventral substantia nigra. The current study used diffusion tensor imaging (DTI) to provide the first in vivo assessment of age-related degeneration in specific segments of the substantia nigra of humans. Measures extracted from DTI of 16 young adults (19-27 years) and 15 older adults (55-71 years) showed that in the dorsal substantia nigra, fractional anisotropy was reduced and radial diffusivity was increased with age. In the ventral substantia nigra and red nucleus, there were no differences across age for the DTI measures. DTI provides a noninvasive technique that accurately reflects the established pattern of age-related cell loss in the dorsal and ventral substantia nigra, further suggesting the robust potential for using DTI to characterize degeneration in the nigrostriatal pathway in both health and disease.     

Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review

Diffusion tensor imaging (DTI) maps the brain's microstructure by measuring fractional anisotropy (FA) and mean diffusivity (MD). This systematic review describes brain diffusion tensor Magnetic resonance imaging (MRI) studies in systemic lupus erythematosus (SLE).The literature was reviewed following the PRISMA guidelines and using the terms “lupus”, “systemic lupus erythematosus”, “SLE”, “diffusion tensor imaging”, “DTI”, “white matter” (WM), “microstructural damage”, “tractography”, and “fractional anisotropy”; the search included articles published in English from January 2007 to April 2017. The subjects included in the study were selected according to the ACR criteria and included 195 SLE patients with neuropsychiatric manifestation (NPSLE), 299 without neuropsychiatric manifestation (non-NPSLE), and 423 healthy controls (HC). Most studies identified significantly reduced FA and increased MD values in several WM regions of both NPSLE and non-NPSLE patients compared to HC. Subclinical microstructural changes were observed in either regional areas or the entire brain in both the non-NPSLE and NPSLE groups.     

1.5TMR肾脏弥散张量成像b值的优化研究

目的 探讨b值的选取对DTI测量指标和图像质量的影响,从而获得最佳b值。方法随机招募20例健康志愿者行DTI成像,b值的选择为0、200、400、600、800、1000s／mm^2,弥散梯度方向为6,分别测量ADC值、FA值,SNR、CNR,对ADC图进行评分,分析不同b值时的变化规律。结果5组b值获得的肾实质、皮质、髓质的ADC值及SNR值比较具有统计学意义（F值为1846．65、368．93、207．80和951．93,P〈0．05）,随着b值的增大,ADC值变小,SNR值变小。不同b值的肾实质、皮质、髓质的FA值及CNR值比较均不具有统计学意义（F值为0．98、1．07、1．14和1．13,P〉0．05）。相同b值时皮、髓质ADC值和FA值比较均具有统计学意义（P〈0．05）。ADC图得分随着b值的增大,图像质量变差。b值取0、800s／mm^2时,ADC图的图像质量具有诊断意义,但皮髓质分辨不清晰。b值与肾实质ADC值、SNR上呈负相关（r=-0．980和-0．974,P〈0．05）,而与FA值、CNR无相关（r=-0．156和-0．152,P〉0．05）。结论b值为600s／mm^2的图像质量较好,皮髓质差异容易分辨,适合于肾脏的研究。     

User‐independent diffusion tensor imaging analysis pipelines in a rat model presenting ventriculomegalia: A comparison study

Automated analysis of diffusion tensor imaging (DTI) data is an appealing way to process large datasets in an unbiased manner. However, automation can sometimes be linked to a lack of interpretability. Two whole‐brain, automated and voxelwise methods exist: voxel‐based analysis (VBA) and tract‐based spatial statistics (TBSS). In VBA, the amount of smoothing has been shown to influence the results. TBSS is free of this step, but a projection procedure is introduced to correct for residual misalignments. This projection assigns the local highest fractional anisotropy (FA) value to the mean FA skeleton, which represents white matter tract centers. For both methods, the normalization procedure has a major impact. These issues are well documented in humans but, to our knowledge, not in rodents. In this study, we assessed the quality of three different registration algorithms (ANTs SyN, DTI‐TK and FNIRT) using study‐specific templates and their impact on automated analysis methods (VBA and TBSS) in a rat pup model of diffuse white matter injury presenting large unilateral deformations. VBA and TBSS results were stable and anatomically coherent across the three pipelines. For VBA, in regions around the large deformations, interpretability was limited because of the increased partial volume effect. With TBSS, two of the three pipelines found a significant decrease in axial diffusivity (AD) at the known injury site. These results demonstrate that automated voxelwise analyses can be used in an animal model with large deformations.     

Computer aided diagnosis system for Alzheimer disease using brain diffusion tensor imaging features selected by Pearson's correlation

The aim of this paper is to obtain discriminant features from two scalar measures of Diffusion Tensor Imaging (DTI) data, Fractional Anisotropy (FA) and Mean Diffusivity (MD), and to train and test classifiers able to discriminate Alzheimer's Disease (AD) patients from controls on the basis of features extracted from the FA or MD volumes. In this study, support vector machine (SVM) classifier was trained and tested on FA and MD data. Feature selection is done computing the Pearson's correlation between FA or MD values at voxel site across subjects and the indicative variable specifying the subject class. Voxel sites with high absolute correlation are selected for feature extraction. Results are obtained over an on-going study in Hospital de Santiago Apostol collecting anatomical T1-weighted MRI volumes and DTI data from healthy control subjects and AD patients. FA features and a linear SVM classifier achieve perfect accuracy, sensitivity and specificity in several cross-validation studies, supporting the usefulness of DTI-derived features as an image-marker for AD and to the feasibility of building Computer Aided Diagnosis systems for AD based on them.     

Elevating tensor rank increases anisotropy in brain areas associated with intra-voxel orientational heterogeneity (IVOH): a generalised DTI (GDTI) study

Rank-2 tensors are unable to represent multi-modal diffusion associated with intra-voxel orientational heterogeneity (IVOH), which occurs where axons are incoherently oriented, such as where bundles intersect or diverge. Under this condition, they are oblate or spheroidally shaped, resulting in artefactually low anisotropy, potentially masking reduced axonal density, myelinisation and integrity. Higher rank tensors can represent multi-modal diffusion, and suitable metrics such as generalised anisotropy (GA) and scaled entropy (SE) have been introduced. The effect of tensor rank was studied through simulations, and analysing high angular resolution diffusion imaging (HARDI) data from two volunteers, fit with rank-2, rank-4 and rank-6 tensors. The variation of GA and SE as a function of rank was investigated through difference maps and region of interest (ROI)-based comparisons. Results were correlated with orientation distribution functions (ODF) reconstructed with q-ball, and with colour-maps of the principal and second eigenvectors. Simulations revealed that rank-4 tensors are able to represent multi-modal diffusion, and that increasing rank further has a minor effect on measurements. IVOH was detected in subcortical regions of the corona radiata, along the superior longitudinal fasciculus, in the radiations of the genu of the corpus callosum, in peritrigonal white matter and along the inferior fronto-occipital and longitudinal fascicula. In these regions, elevating tensor rank increased anisotropy. This was also true for the corpus callosum, cingulum and anterior limb of the internal capsule, where increasing tensor rank resulted in patterns that, although mono-modal, were more anisotropic. In these regions the second eigenvector was coherently oriented. As rank-4 tensors have only 15 distinct elements, they can be determined without acquiring a large number of directions. By removing artefactual underestimation of anisotropy, their use may increase the sensitivity to pathological change.     

弥散张量磁共振成像的新进展

弥散张量磁共振成像技术是近年来出现的一项新技术,由于其对脑白质纤维具有高度敏感性以致在临床上的应用日益广泛,并为人体中枢神经系统的深入研究提供了有效的工具。     

Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder

Background

Diffusion tensor imaging (DTI) studies have shown changes in the microstructure of white matter in bipolar disorder. Studies suggest both localised, predominantly fronto-limbic, as well as more widespread changes in white matter, but with some apparent inconsistency. A meta-analysis of white matter alterations in adults with bipolar disorder was undertaken.

Method

Whole-brain DTI studies comparing adults with bipolar disorder to healthy controls on fractional anisotropy (FA) were retrieved using searches of MEDLINE and EMBASE from between 2003 and December 2012. White-matter tract involvement was collated and quantified. Clusters of significantly altered FA were meta-analysed using effect-size signed differential mapping (ES-SDM).

Results

Ten VBA studies (252 patients and 256 controls) and five TBSS studies (138 patients and 98 controls) met inclusion criteria. Sixty-one clusters of significantly different FA between bipolar disorder and healthy controls were identified. Analysis of white-matter tracts indicated that all major classes of tracts are implicated. ES-SDM meta-analysis of VBA studies revealed three significant clusters of decreased FA in bipolar disorder (a right posterior temporoparietal cluster and two left cingulate clusters). Findings limited to the Bipolar Type I papers were more robust.

Limitations

Voxel-based studies do not accurately identify tracts, and our ES-SDM analysis used only published peak voxels rather than raw DTI data.

Conclusions

There is consistent data indicating widespread white matter involvement with decreased white matter FA demonstrated in three disparate areas in bipolar disorder. White matter alterations are not limited to anterior fronto-limbic pathways in bipolar disorder.     

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.     

Fractional anisotropy and mean diffusivity: comparison between 3.0-T and 1.5-T diffusion tensor imaging with parallel imaging using histogram and region of interest analysis

We performed a comparison study focusing on differences in fractional anisotropy (FA) and mean diffusivity (MD) between 3-T and 1.5-T diffusion tensor imaging (DTI) with parallel imaging. Thirty healthy volunteers underwent DTI with an eight-channel phased-array coil at both 3 T and 1.5 T. Histogram and region of interest (ROI) analyses were performed. Paired t tests were applied for statistical analysis. Signal-to-noise ratios of these regions were also measured. For histogram analysis, peak location of FA was significantly lower at 3 T than at 1.5 T (P = 0.04). Mean FA was significantly higher at 3 T than at 1.5 T (P = 0.002). Peak location of MD was significantly lower at 3 T than at 1.5 T (P < 0.001). Mean MD was significantly lower at 3 T than at 1.5 T (P < 0.001). In ROI analysis, FA was significantly larger at 3 T than at 1.5 T in the centrum semiovale (P < 0.001), middle cerebellar peduncle (P < 0.001), cerebral peduncle (P = 0.006), posterior limb of the internal capsule (P = 0.007), genu (P < 0.001) and splenium (P < 0.001). FA was significantly lower at 3 T than at 1.5 T in the globus pallidus (P < 0.001). MD was significantly smaller at 3 T than at 1.5 T in the globus pallidus (P = 0.007), thalamus (P < 0.001), centrum semiovale (P < 0.001), middle cerebellar peduncle (P < 0.001), cerebral peduncle (P = 0.01), posterior limb of the internal capsule (P < 0.001), genu (P = 0.01) and splenium (P < 0.001). Significant differences in FA and MD exist between 3 T and 1.5 T for whole-brain histogram analysis and ROI analysis.     

Assessment of the diagnostic value of diffusion tensor imaging in patients with spinal cord compression: a meta-analysis

We investigated the diagnostic value of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging (DTI) in patients with spinal cord compression (SCC) using a meta-analysis framework. Multiple scientific literature databases were exhaustively searched to identify articles relevant to this study. Mean values and standardized mean differences (SMDs) were calculated for the ADC and FA in normal and diseased tissues. The STATA version 12.0 software was used for statistical analysis. Of the 41 articles initially retrieved through database searches, 11 case-control studies were eligible for the meta-analysis and contained a combined total of 645 human subjects (394 patients with SCC and 251 healthy controls). All 11 studies reported data on FA, and 9 contained data related to the ADC. The combined SMDs of the ADC and FA showed that the ADC was significantly higher and the FA was lower in patients with SCC than in healthy controls. Subgroup analysis based on the b value showed higher ADCs in patients with SCC than in healthy controls at b values of both ≤500 and >500 s/mm². In summary, the main findings of this meta-analysis revealed an increased ADC and decreased FA in patients with SCC, indicating that DTI is an important diagnostic imaging tool to assess patients suspected to have SCC.     

腰椎间盘MR扩散张量成像及其定量分析

目的　研究正常成人腰椎间盘MR扩散张量成像及其量化特征。 方法 采用Philips 1.5T超导MR成像系统,对20例健康志愿者的L1/2～L5/S1椎间盘进行扫描,得到常规T1W、T2W,DTI扫描采用单次激发SE-EPI序列,扫描后处理获得纤维环示踪图（DTT）、FA彩图、FA图、e ADC图、Trance D图,观察DTT图上纤维环形态,通过ADC值、Trace D值、FA值的测量,定量分析纤维环、髓核的扩散特征。 结果　应用MR扩散张量成像可获取椎间盘纤维示踪图（DTT）、FA彩图、FA图、e ADC图、Trance D图,正常纤维环呈连续、规则均匀的环形,不同板层纤维束呈交错排列。纤维环的FA值显著高于髓核FA值(P<0.05),髓核Trace值显著高于纤维环(P<0.05),在髓核和纤维环内,轴向扩散高于放射状扩散　(P<0.05),腰椎不同节段椎间盘内髓核、纤维环的扩散特征无显著性差别(P>0.05)。 结论　磁共振DTI能够显示纤维环内纤维束板层形态、排列;纤维环和髓核具有不同的扩散特征,纤维环的各向异性更显著,髓核更易于发生扩散;椎间盘内的主要扩散方向呈轴向。     

Gray matter density and white matter integrity in pianists' brain: a combined structural and diffusion tensor MRI study

The current study combined structural magnetic resonance imaging (sMRI) and diffusion tensor MRI (DT-MRI) to investigate both gray matter density (GMD) and white matter integrity (WMI) in 18 pianists and 21 age-matched non-musicians. The pianists began their piano training at a mean age of 12. Voxel-based morphometry of the sMRI data showed that the pianists had higher GMD in the left primary sensorimotor cortex and right cerebellum. Voxel-based analysis of the DT-MRI data showed that pianists had higher fractional anisotropy (FA) (indicating higher WMI) in the right posterior limb of the internal capsule. The sMRI and DT-MRI results indicate that both the GMD and WMI of pianists may exhibit movement-related increases during adolescence or even early adulthood compared with non-musicians.     

Prognosis of cervical myelopathy based on diffusion tensor imaging with artificial intelligence methods

Diffusion tensor imaging (DTI) has been proposed for the prognosis of cervical myelopathy (CM), but the manual analysis of DTI features is complicated and time consuming. This study evaluated the potential of artificial intelligence (AI) methods in the analysis of DTI for the prognosis of CM. Seventy‐five patients who underwent surgical treatment for CM were recruited for DTI imaging and were divided into two groups based on their one‐year follow‐up recovery. The DTI features of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were extracted from DTI maps of all cervical levels. Conventional AI models using logistic regression (LR), k‐nearest neighbors (KNN), and a radial basis function kernel support vector machine (RBF‐SVM) were built using these DTI features. In addition, a deep learning model was applied to the DTI maps. Their performances were compared using 50 repeated 10‐fold cross‐validations. The accuracy of the classifications reached 74.2% ± 1.6% for LR, 85.6% ± 1.4% for KNN, 89.7% ± 1.6% for RBF‐SVM, and 59.2% ± 3.8% for the deep leaning model. The RBF‐SVM algorithm achieved the best accuracy, with sensitivity and specificity of 85.0% ± 3.4% and 92.4% ± 1.9% respectively. This finding indicates that AI methods are feasible and effective for DTI analysis for the prognosis of CM.