The effects of brain tissue decomposition on diffusion tensor imaging and tractography

There have been numerous high resolution diffusion tensor imaging studies in fixed animal brains, but relatively few studies in human brains. While animal tissues are generally fixed pre-mortem or directly postmortem, this is not possible for human tissue, therefore there is always some delay between death and tissue fixation. The elapsed time between death and tissue fixation, the postmortem interval (PMI), will most likely adversely affect the tissue's diffusion properties. We studied the effects of PMI on the diffusion properties of rodent brain. Eight mice were euthanized and the brains (kept in the skull) were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography was also performed. The temporal changes in regional ADC and FA values were analyzed statistically using a one-way ANOVA, followed by individual Student's T-tests. Regional FA and ADC of gray and white matter decreased significantly with time (p<0.05). DTI tractography showed a decrease in the number and coherence of reconstructed fiber pathways between PMIs 0 and 14. Elapsed time between death and tissue fixation has a major effect upon the brain's diffusion properties and should be born in mind when interpreting fixed brain DTI.     

DeepSTI: Towards tensor reconstruction using fewer orientations in susceptibility tensor imaging

Susceptibility tensor imaging (STI) is an emerging magnetic resonance imaging technique that characterizes the anisotropic tissue magnetic susceptibility with a second-order tensor model. STI has the potential to provide information for both the reconstruction of white matter fiber pathways and detection of myelin changes in the brain at mm resolution or less, which would be of great value for understanding brain structure and function in healthy and diseased brain. However, the application of STI in vivo has been hindered by its cumbersome and time-consuming acquisition requirement of measuring susceptibility induced MR phase changes at multiple head orientations. Usually, sampling at more than six orientations is required to obtain sufficient information for the ill-posed STI dipole inversion. This complexity is enhanced by the limitation in head rotation angles due to physical constraints of the head coil. As a result, STI has not yet been widely applied in human studies in vivo. In this work, we tackle these issues by proposing an image reconstruction algorithm for STI that leverages data-driven priors. Our method, called DeepSTI, learns the data prior implicitly via a deep neural network that approximates the proximal operator of a regularizer function for STI. The dipole inversion problem is then solved iteratively using the learned proximal network. Experimental results using both simulation and in vivo human data demonstrate great improvement over state-of-the-art algorithms in terms of the reconstructed tensor image, principal eigenvector maps and tractography results, while allowing for tensor reconstruction with MR phase measured at much less than six different orientations. Notably, promising reconstruction results are achieved by our method from only one orientation in human in vivo, and we demonstrate a potential application of this technique for estimating lesion susceptibility anisotropy in patients with multiple sclerosis.     

扩散张量成像在脑脓肿诊断中的价值

目的评价MR扩散张量成像在脑脓肿中的应用价值. 方法经病理及临床复查证实的脑脓肿9例.行常规MR扫描、扩散张量成像(DTI)检查.构建平均扩散系数(ADC)图和各向异性分数(FA)图,并测量脓肿及周围水肿区的ADC、FA值.结果在扩散张量加权像上,脓肿腔表现为高信号,水肿区呈低信号;在ADC图上,脓肿呈低信号,平均ADC值为(0.66±0.07)×10-3mm2/s,水肿区呈高信号;在FA图上,脓肿与水肿均表现为低信号.结论在DTI扩散张量加权像上,脓肿表现为较特异的高信号,ADC值较低,有助于和囊变、坏死性肿瘤鉴别.     

磁共振扩散张量成像在显示正常人脑白质纤维中的应用

目的应用DTI技术显示正常人脑白质纤维,探讨其与解剖学描述的一致性。方法20名健康志愿者行颅脑MRI与颅脑单次激发回波平面扩散张量成像扫描(b值=0,500s/mm2),在SiemensLeonardo工作站应用纤维束跟踪软件(SiemensStandar12dirs)进行后处理重建出白质纤维束。结果对主要白质纤维如皮质脊髓束、皮质核束、胼胝体、扣带、上纵束、下纵束、上枕额束、下枕额束、钩束进行模拟显示,不同纤维需要选择适合的感兴趣区、各向异性阈值、角度阈值、步长和体素内采样数目等参数,显示结果与解剖学描述具有较好的一致性。结论利用扩散张量成像技术可模拟显示正常人脑白质纤维,与解剖学描述具有较好的一致性,是在活体中研究人脑白质纤维的一种较可靠的方法。     

Optimizing tissue clearing and imaging methods for human brain tissue

ObjectivesTo identify optimum sample conditions for human brains, we compared the clearing efficiency, antibody staining efficiency, and artifacts between fresh and cadaver samples.MethodsFresh and cadaver samples were cleared using X-CLARITY™. Clearing efficiency and artifact levels were calculated using ImageJ, and antibody staining efficiency was evaluated after confocal microscopy imaging. Three staining methods were compared: 4-day staining (4DS), 11-day staining (11DS), and 4-day staining with a commercial kit (4DS-C). The optimum staining method was then selected by evaluating staining time, depth, method complexity, contamination, and cost.ResultsFresh samples outperformed cadaver samples in terms of the time and quality of clearing, artifacts, and 4′,6-diamidino-2-phenylindole (DAPI) staining efficiency, but had a glial fibrillary acidic protein (GFAP) staining efficiency that was similar to that of cadaver samples. The penetration depth and DAPI staining improved in fresh samples as the incubation period lengthened. 4DS-C was the best method, with the deepest penetration. Human brain images containing blood vessels, cell nuclei, and astrocytes were visualized three-dimensionally. The chemical dye staining depth reached 800 µm and immunostaining depth exceeded 200 µm in 4 days.ConclusionsWe present optimized sample preparation and staining protocols for the visualization of three-dimensional macrostructure in the human brain.     

Automated fiber tracking of human brain white matter using diffusion tensor imaging

Reconstruction of white matter tracts based on diffusion tensor imaging (DTI) is currently widely used in clinical research. This reconstruction allows us to identify coordinates of specific white matter tracts and to investigate their anatomy. Fiber reconstruction, however, relies on manual identification of anatomical landmarks of a tract of interest, which is based on subjective judgment and thus a potential source of experimental variability. Here, an automated tract reconstruction approach is introduced. A set of reference regions of interest (rROIs) known to select a tract of interest was marked in our DTI brain atlas. The atlas was then linearly transformed to each subject, and the rROI set was transferred to the subject for tract reconstruction. Agreement between the automated and manual approaches was measured for 11 tracts in 10 healthy volunteers and found to be excellent (kappa>0.8) and remained high up to 4-5 mm of the linear transformation errors. As a first example, the automated approach was applied to brain tumor patients and strategies to cope with severe anatomical abnormalities are discussed.     

基于弥散张量成像技术构建人脑结构网络的研究进展

脑网络是复杂网络理论在神经科学研究中的重要应用,脑网络的构建与分析为脑疾病的预测、诊断及预后评价等提供了新的视角。弥散张量成像技术作为一种无创性展现脑白质纤维束形态的成像技术,现已被应用于脑网络的研究中。本文基于弥散张量成像技术构建大脑结构网络的研究进展做一综述。     

3D fiber tractography with susceptibility tensor imaging

Gradient-echo MRI has revealed anisotropic magnetic susceptibility in the brain white matter. This magnetic susceptibility anisotropy can be measured and characterized with susceptibility tensor imaging (STI). In this study, a method of fiber tractography based on STI is proposed and demonstrated in the mouse brain. STI experiments of perfusion-fixed mouse brains were conducted at 7.0 T. The magnetic susceptibility tensor was calculated for each voxel with regularization and decomposed into its eigensystem. The major eigenvector is found to be aligned with the underlying fiber orientation. Following the orientation of the major eigenvector, we are able to map distinctive fiber pathways in 3D. As a comparison, diffusion tensor imaging (DTI) and DTI fiber tractography were also conducted on the same specimens. The relationship between STI and DTI fiber tracts was explored with similarities and differences identified. It is anticipated that the proposed method of STI tractography may provide a new way to study white matter fiber architecture. As STI tractography is based on physical principles that are fundamentally different from DTI, it may also be valuable for the ongoing validation of DTI tractography.     

Cell-oriented analysis in vivo using diffusion tensor imaging for normal-appearing brain tissue in multiple sclerosis

There have been several methods proposed so far using diffusion tensor imaging (DTI) for the assessment of normal-appearing brain tissue (NABT) injury in multiple sclerosis (MS). However, for these methods, the analyses of the NABT injury at the cellular level, wherein histological examinations can be used, still present challenging problems. We developed a method of segregating NABT into the following anatomical structures using lambda chart analysis associated with a two-dimensional Gaussian deconvolution of diffusion characteristic functions: 1) structures primarily composed of small neurons and glia; 2) structures primarily composed of large neurons; 3) structures primarily composed of short axons; and 4) structures primarily composed of long axons. Each segregated structure that had a distinctive diffusion characteristic was subjected to the statistical inference of DTI-derived parameters for 14 patients with conventional relapsing-remitting MS (RRMS) and 20 age-matched healthy volunteers. In all of the structures, the trace values were significantly higher and the fractional anisotropy values were significantly lower in the RRMS patients than in the healthy volunteers. Furthermore, the volume fractions of the structures primarily composed of short axons markedly decreased, whereas those of the structures primarily composed of small neurons and glia markedly increased. These results suggest that axonal loss and glial proliferation predominantly occurred in the subcortical white matter and adjacent deep cortical layer, namely, the juxtacortical region. This cell-oriented analysis of NABT injury using DTI confirmed in vivo the histological observation that the juxtacortical region is the most vulnerable site in MS.     

In vivo diffusion tensor imaging (DTI) of brain subdivisions and vocal pathways in songbirds

The neural substrate for song behavior in songbirds, the song control system (SCS), is thus far the best-documented brain circuit in which to study neuroplasticity and adult neurogenesis. Not only does the volume of the key song control nuclei change in size, but also the density of the connections between them changes as a function of seasonal and hormonal influences. This study explores the potentials of in vivo Diffusion-Tensor MRI (DT-MRI or DTI) to visualize the distinct, concentrated connections of the SCS in the brain of the starling (Sturnus vulgaris). In vivo DTI on starling was performed on a 7T MR system using sagittal and coronal slices. DTI was accomplished with diffusion gradients applied in seven non-collinear directions. Fractional Anisotropy (FA)-maps allowed us to distinguish most of the grey matter and white matter-tracts, including the laminae subdividing the avian telencephalon and the tracts connecting the major song control nuclei (e.g., HVC with RA and X). The FA-maps also allowed us to discern a number of song control, auditory and visual nuclei. Fiber tracking was implemented to illustrate the discrimination of all tracts running from and to RA. Because of the remarkable plasticity inherent to the songbird brain, the successful implementation of DTI in this model could represent a useful tool for the in vivo exploration of fiber degeneration and regeneration and the biological mechanisms involved in brain plasticity.     

不同b值在正常人脑组织磁共振扩散张量成像中的应用探讨

目的获取正常人脑组织磁共振扩散张量图像,评价不同b值条件下的扩散张量图像改变。方法筛选28例正常(常规MR显示未见异常者)健康成年人,分别选取b=1000s/mm2,b=2000s/mm2和b=3000s/mm2同时进行磁共振扩散张量成像(DTI),应用Philips公司提供的分析软件分析扩散张量图。包括:各向同性表面扩散系数(ADCiso)图和各向异性图,测量不同b值时图像的信躁比(SNR)及灰白质对比度。结果随着b值的升高,各相同性图及ADCiso图均显示脑组织灰白质对比度增高,b=2000s/mm2组(或b=3000s/mm2组)与b=1000s/mm2组有显著差异(P<0.001),b=2000s/mm2组与b=3000s/mm2组无显著差异(P>0.05)。结论①b=1000s/mm2时,DTI图像质量最好,但脑组织灰白质对比度不高。②b=2000s/mm2时,DTI图像质量较好,对比度较佳,能提供更多的扩散信息,更好地反应脑组织内水分子的扩散特性。③b=3000s/mm2时,DTI图像质量较差,对比度最好,但与b=2000s/mm2组差异不显著(P>0.05),而且增加扫描时间。笔者认为扩散梯度因子b=2000s/mm2时,图像综合质量最优,建议常规应用。     

Quantitative susceptibility mapping of human brain reflects spatial variation in tissue composition

Image phase from gradient echo MRI provides a unique contrast that reflects brain tissue composition variations, such as iron and myelin distribution. Phase imaging is emerging as a powerful tool for the investigation of functional brain anatomy and disease diagnosis. However, the quantitative value of phase is compromised by its nonlocal and orientation dependent properties. There is an increasing need for reliable quantification of magnetic susceptibility, the intrinsic property of tissue. In this study, we developed a novel and accurate susceptibility mapping method that is also phase-wrap insensitive. The proposed susceptibility mapping method utilized two complementary equations: (1) the Fourier relationship of phase and magnetic susceptibility; and (2) the first-order partial derivative of the first equation in the spatial frequency domain. In numerical simulation, this method reconstructed the susceptibility map almost free of streaking artifact. Further, the iterative implementation of this method allowed for high quality reconstruction of susceptibility maps of human brain in vivo. The reconstructed susceptibility map provided excellent contrast of iron-rich deep nuclei and white matter bundles from surrounding tissues. Further, it also revealed anisotropic magnetic susceptibility in brain white matter. Hence, the proposed susceptibility mapping method may provide a powerful tool for the study of brain physiology and pathophysiology. Further elucidation of anisotropic magnetic susceptibility in vivo may allow us to gain more insight into the white matter micro-architectures.     

弥散张量成像在胎儿脑发育中的研究进展

胎脑从妊娠第3周末一个简单的神经管结构发育成出生后功能结构复杂的脑组织,期间经历了脑原始诱导发育、神经细胞增殖、神经元移行、两侧大脑半球皮质层状结构形成、脑室、沟、裂、脑回发育,以及白质纤维出现到成熟的髓鞘化过程。这些发育过程极其精确复杂,但是遵从严格的顺序。产前超声仅能筛查早期胎脑较明显的先天异常,无法评估这些细微的脑结构发育情况。近年来发展的磁共振成像技术为胎脑发育的研究提供了有用工具,尤其是弥散张量成像技术通过检测脑组织的水分子弥散运动,提供了从微观结构层面观察胎脑信息的视角,同胎脑组织学研究形成互补。本文将简要介绍弥散张量成像(diffusion tensor imaging,DTI)技术应用于胎脑方面的优势及其主要应用手段,DTI对皮质层状结构的显示,以及显示白质纤维束出现的时间、顺序、胎脑纤维束连接的变化、白质髓鞘化前成熟过程等,还总结了目前DTI技术用于胎儿脑成像的主要技术难题与解决办法,为进一步应用弥散张量成像研究正常胎儿脑发育奠定理论基础。     

Diffusion tensor magnetic resonance imaging of brain tumors

DTI seems to offer the possibility of adding important information to presurgical planning. Although experience is limited, DTI seems to provide useful local information about the structures near the tumor, and this seems to be useful in planning. In the future, DTI may provide an improved way to monitor intraoperative surgical procedures as well as their complications. Furthermore, evaluation of the response to treatment with chemotherapy and radiation therapy might also be possible. Although DTI has some limitations, its active investigation and further study are clearly warranted.     

Diffusion tensor imaging segments the human amygdala in vivo

The amygdala plays an important role in emotion, learning, and memory. It would be highly advantageous to understand more precisely its internal structure and connectivity for individual human subjects in vivo. Earlier cytoarchitectural research in post-mortem human and animal brains has revealed multiple subdivisions and connectivity patterns, probably related to different functions. With standard magnetic resonance imaging (MRI) techniques, however, the amygdala appears as an undifferentiated area of grey matter. Using high-quality diffusion tensor imaging (DTI) at 3 Tesla, we show diffusion anisotropy in this grey matter area. Such data allowed us to subdivide the amygdala for the first time in vivo. In 15 living subjects, we applied a spectral clustering algorithm to the principal diffusion direction in each amygdala voxel and found a consistent subdivision of the amygdala into a medial and a lateral region. The topography of these regions is in good agreement with the fibre architecture visible in myelin-stained sections through the amygdala of a human post-mortem brain. From these in vivo results we derived a probabilistic map of amygdalar fibre orientations. This segmentation technique has important implications for functional studies in the processing of emotions, cognitive function, and psychiatric disorders and in studying morphometry and volumetry of amygdala subdivisions.     

轻度创伤性脑损伤患者动态扩散张量成像的演变规律

目的通过观察轻度创伤性脑损伤(TBI)患者DTI动态变化规律,探讨其在反映TBI病理生理学改变、病程发展方面的应用价值.方法对35例轻度TBI患者和35名健康对照者行常规MR、DTI检查.测量TBI患者(急性期、亚急性期、伤后5周～3个月)和对照者多个脑区的FA值、ADC值并进行比较,观察各测量值动态变化规律.结果 轻度TBI患者部分脑叶白质和脑干区的FA值在急性期、亚急性期时减低(P均<0.05),伤后5周～3个月时略低于对照者(P均>0.05),但急性期时胼胝体、内囊的FA值高于对照者(P均>0.05),此后持续减低,在伤后5周～3个月时差异仍具有统计学意义(P均<0.05).ADC值大致呈现为急性期减低,亚急性期及伤后5周～3个月逐渐升高(P均>0.05)的趋势.结论FA值减低反映神经轴索损伤,但急性期轻度TBI患者的胼胝体、内囊处FA值略升高,提示存在细胞毒性<水肿.ADC值反映轴索损伤不及FA值敏感、准确.     

人脑连合纤维的弥散张量纤维束成像

目的建立弥散张量纤维束成像对人脑连合纤维的显示方法,探讨显示结果与已知解剖知识的一致性.方法对1个正常志愿者进行单次激发回波平面弥散张量成像,利用纤维束成像软件包显示脑内连合纤维,观察重建的连合纤维与已知解剖知识的一致性.结果通过选择恰当的感兴趣区,设置不同的分数各向异性阈值、角度阈值、步长和体素内采样数目等参数,弥散张量纤维束成像可以清楚地显示胼胝体、穹隆和前连合等连合纤维的三维结构.显示结果与已知解剖知识具有良好的一致性.结论纤维束成像的结果与解剖学描述具有高度一致性,该方法是一种可靠的研究人脑纤维连接的方法.     

Direct quantitative comparison between cross-relaxation imaging and diffusion tensor imaging of the human brain at 3.0 T

Cross-relaxation imaging (CRI) describes the magnetization transfer within tissues between mobile water protons and macromolecular protons. Whole-brain parametric maps of the principle kinetic components of magnetization transfer, the fraction of macromolecular protons (f) and the rate constant (k), revealed detailed anatomy of white matter (WM) fiber tracts at 1.5 T. In this study, CRI was first adapted to 3.0 T, and constraints for transverse relaxation times of water and macromolecular protons were identified to enable unbiased f and k estimation. Subsequently, whole-brain CRI and diffusion tensor imaging (DTI) were performed in five healthy subjects. The parameters f and k were compared to DTI indices (fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD)) across a range of anatomic regions. In WM, neither f nor k was significantly correlated to FA, RD, and AD. In contrast, both f (r = 0.90 and r = − 0.80) and k (r = 0.92 and r = − 0.89) in gray matter (GM) were strongly correlated to FA and RD, respectively. A moderate correlation between ADC and k (r = 0.48) was identified in WM, while an inverse correlation was identified in GM (r = − 0.72). The lack of association between CRI and FA in WM is consistent with differences in the underlying physical principles between techniques — fiber density vs. directionality, respectively. The association in GM may be attributable to variable axonal density unique to each structure. Our findings suggest that whole-brain CRI provides distinct quantitative information compared to DTI, and CRI parameters may prove constructive as biomarkers in neurological diseases.     

磁共振扩散张量成像在新生儿脑发育的应用及展望

扩散张量成像(DTI)是一种十分敏感的、可以多参数量化检测局部水分子扩散特征的方法。本文回顾了DTI的基本原理,及DTI数据常用的分析方法,总结了新生儿、早产儿,脑灰质、脑白质发育过程中DTI参数的变化规律,显示DTI能够良好反映新生儿脑发育时的各种生理学变化,有望成为量化评价脑白质发育的有效工具。     

磁共振弥散张量成像技术在新生儿脑白质发育中的研究

目的运用磁共振弥散张量成像(DTI)技术研究分析新生儿脑白质发育规律和特点。材料与方法本研究纳入38名新生儿,包括18例适于胎龄早产儿,20例正常出生体重足月儿,按胎龄分为3组,分别测量各兴趣区FA值进行分析。结果新生儿脑实质FA值无左右差异。外周白质FA值小于深部白质,在深部脑白质中,胼胝体压部FA值高于膝部,内囊后肢高于前肢,胼胝体压部高于内囊后肢;在外周脑白质中,半卵圆中心层面中部白质FA值最高,半卵圆中心前、后白质的FA值均无统计学差异(P0.05)。Ⅲ组各兴趣区FA值均高于Ⅰ组,且差异有统计学意义(P0.05),相邻胎龄组比较,只有部分兴趣区有统计学差异。结论 DTI技术在研究新生儿脑白质成熟方面具有重要价值,FA值可定量评估髓鞘发育。