基于扩散磁共振成像的纤维追踪技术为非侵入性观测脑白质结构提供了有力的手段，约束球面反卷积作为一种多纤维追踪模型，能够对体素内纤维的方向信息进行建模，进而实现脑纤维的重构.针对约束球面反卷积模型的不适定性以及细节信息丢失问题，本文在约束球面反卷积的基础上，结合邻域信息和分数阶正则化，提出了一种基于非局部约束球面反卷积模型的确定型纤维追踪算法，分数阶的非局部特性使得纤维方向分布模型估计的误差更小，而邻域信息的引入保证了空间一致性，可以减少噪声的影响.分别利用模拟数据、人脑实际数据对本文算法及基于约束球面反卷积的确定型纤维追踪算法作对比实验，结果表明，利用本文算法追踪的纤维不仅整体视觉效果上较整洁，而且对交叉纤维的重建结果更完整准确.

扩散张量脑模板包含丰富的大脑白质组织信息，在空间标准化或者脑图谱创建中具有重要价值，然而基于扩散张量模型构建的脑模板精度不高，特别是在脑部复杂的神经元微观结构区域中应用受到限制.针对这一问题，研究者们提出了基于高分辨率扩散成像构建大脑模板的方法.本文对使用扩散张量成像方法进行脑模板构建的研究进展进行了综述，首先介绍了扩散张量脑模板构建的发展进程，阐述了脑模板构建中解决的技术问题及同时存在的局限性；接着详细论述了基于扩散频谱成像及高角度分辨率扩散成像构建脑模板的不同方法间的差异，并总结了这些研究方法取得的重要进展；最后通过分析目前研究进展提出该研究问题中存在的不足以及未来的发展趋势.

We describe a framework for creating a time-resolved group average template of the developing brain using advanced multi-shell high angular resolution diffusion imaging data, for use in group voxel or fixel-wise analysis, atlas-building, and related applications. This relies on the recently proposed multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD) technique. We decompose the signal into one isotropic component and two anisotropic components, with response functions estimated from cerebrospinal fluid and white matter in the youngest and oldest participant groups, respectively. We build an orientationally-resolved template of those tissue components from data acquired from 113 babies between 33 and 44 weeks postmenstrual age, imaged as part of the Developing Human Connectome Project. These data were split into weekly groups, and registered to the corresponding group average templates using a previously-proposed non-linear diffeomorphic registration framework, designed to align orientation density functions (ODF). This framework was extended to allow the use of the multiple contrasts provided by the multi-tissue decomposition, and shown to provide superior alignment. Finally, the weekly templates were registered to the same common template to facilitate investigations into the evolution of the different components as a function of age. The resulting multi-tissue atlas provides insights into brain development and accompanying changes in microstructure, and forms the basis for future longitudinal investigations into healthy and pathological white matter maturation.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Constrained spherical deconvolution (CSD) has become one of the most widely used methods to extract white matter (WM) fibre orientation information from diffusion-weighted MRI (DW-MRI) data, overcoming the crossing fibre limitations inherent in the diffusion tensor model. It is routinely used to obtain high quality fibre orientation distribution function (fODF) estimates and fibre tractograms and is increasingly used to obtain apparent fibre density (AFD) measures. Unfortunately, CSD typically only supports data acquired on a single shell in q-space. With multi-shell data becoming more and more prevalent, there is a growing need for CSD to fully support such data. Furthermore, CSD can only provide high quality fODF estimates in voxels containing WM only. In voxels containing other tissue types such as grey matter (GM) and cerebrospinal fluid (CSF), the WM response function may no longer be appropriate and spherical deconvolution produces unreliable, noisy fODF estimates. The aim of this study is to incorporate support for multi-shell data into the CSD approach as well as to exploit the unique b-value dependencies of the different tissue types to estimate a multi-tissue ODF. The resulting approach is dubbed multi-shell, multi-tissue CSD (MSMT-CSD) and is compared to the state-of-the-art single-shell, single-tissue CSD (SSST-CSD) approach. Using both simulations and real data, we show that MSMT-CSD can produce reliable WM/GM/CSF volume fraction maps, directly from the DW data, whereas SSST-CSD has a tendency to overestimate the WM volume in voxels containing GM and/or CSF. In addition, compared to SSST-CSD, MSMT-CSD can substantially increase the precision of the fODF fibre orientations and reduce the presence of spurious fODF peaks in voxels containing GM and/or CSF. Both effects translate into more reliable AFD measures and tractography results with MSMT-CSD compared to SSST-CSD.Copyright © 2014 Elsevier Inc. All rights reserved.

Diffusion-weighted magnetic resonance imaging (diffusion MRI) is being used to characterize morphological development of cells within developing cerebral cortical gray matter. Abnormal morphology is a shared characteristic of cerebral cortical neurons for many neurodevelopmental disorders, and therefore diffusion MRI is potentially of high value for monitoring growth-related anatomical changes of relevance to brain function. Here, the theoretical framework for analyzing diffusion MRI data is summarized. An overview of quantitative methods for validating the interpretations of diffusion MRI data using light microscopy is then presented. These theoretical modeling and validation methods have been used to precisely characterize changes in water diffusion anisotropy with development in the context of several animal model systems. Further, in diffusion MRI studies of several preclinical models of neurodevelopmental disorders, the ability is demonstrated of diffusion MRI to detect abnormal morphological neural development. These animal model studies are reviewed along with recent initial efforts to translate the findings into an approach for studies of human subjects. This body of data indicates that diffusion MRI has the requisite sensitivity to detect abnormal cellular development in the context of several models of neurodevelopmental disorders, and therefore may provide a new strategy for detecting abnormalities in early stages of brain development in humans.Copyright © 2018. Published by Elsevier Inc.

The cortical layers define the architecture of the gray matter and its neuroanatomical regions and are essential for brain function. Abnormalities in cortical layer development, growth patterns, organization, or size can affect brain physiology and cognition. Unfortunately, while large population studies are underway that will greatly increase our knowledge about these processes, current non-invasive techniques for characterizing the cortical layers remain inadequate. For decades, high-resolution T1 and T2 Weighted Magnetic Resonance Imaging (MRI) have been the method-of-choice for gray matter and layer characterization. In the past few years, however, diffusion MRI has shown increasing promise for its unique insights into the fine structure of the cortex. Several different methods, including surface analysis, connectivity exploration, and sub-voxel component modeling, are now capable of exploring the diffusion characteristics of the cortex. In this review, we will discuss current advances in the application of diffusion imaging for cortical characterization and its unique features, with a particular emphasis on its spatial resolution, arguably its greatest limitation. In addition, we will explore the relationship between the diffusion MRI signal and the cellular components of the cortex, as visualized by histology. While the obstacles facing the widespread application of cortical diffusion imaging remain daunting, the information it can reveal may prove invaluable. Within the next few years, we predict a surge in the application of this technique and a concomitant expansion of our knowledge of cortical layers.Copyright © 2018 Elsevier Inc. All rights reserved.

High b value diffusion-weighted images sampled at high angular resolution were analyzed using a composite hindered and restricted model of diffusion (CHARMED). Measurements and simulations of diffusion in white matter using CHARMED provide an unbiased estimate of fiber orientation with consistently smaller angular uncertainty than when calculated using a DTI model or with a dual tensor model for any given signal-to-noise level. Images based on the population fraction of the restricted compartment provide a new contrast mechanism that enhances white matter like DTI. Nevertheless, it is assumed that these images might be more sensitive than DTI to white matter disorders. We also provide here an experimental design and analysis framework to implement CHARMED MRI that is feasible on human clinical scanners.

This paper introduces neurite orientation dispersion and density imaging (NODDI), a practical diffusion MRI technique for estimating the microstructural complexity of dendrites and axons in vivo on clinical MRI scanners. Such indices of neurites relate more directly to and provide more specific markers of brain tissue microstructure than standard indices from diffusion tensor imaging, such as fractional anisotropy (FA). Mapping these indices over the whole brain on clinical scanners presents new opportunities for understanding brain development and disorders. The proposed technique enables such mapping by combining a three-compartment tissue model with a two-shell high-angular-resolution diffusion imaging (HARDI) protocol optimized for clinical feasibility. An index of orientation dispersion is defined to characterize angular variation of neurites. We evaluate the method both in simulation and on a live human brain using a clinical 3T scanner. Results demonstrate that NODDI provides sensible neurite density and orientation dispersion estimates, thereby disentangling two key contributing factors to FA and enabling the analysis of each factor individually. We additionally show that while orientation dispersion can be estimated with just a single HARDI shell, neurite density requires at least two shells and can be estimated more accurately with the optimized two-shell protocol than with alternative two-shell protocols. The optimized protocol takes about 30 min to acquire, making it feasible for inclusion in a typical clinical setting. We further show that sampling fewer orientations in each shell can reduce the acquisition time to just 10 min with minimal impact on the accuracy of the estimates. This demonstrates the feasibility of NODDI even for the most time-sensitive clinical applications, such as neonatal and dementia imaging.Copyright © 2012 Elsevier Inc. All rights reserved.

Microstructure imaging is a technique based on diffusion magnetic resonance imaging to characterize the microstructure of human brain tissue in vivo.It has been widely used in neuroscience research and clinical application.The microstructure imaging model correlates different tissue properties and magnetic resonance signals to estimate the microscopic properties of the tissue.This paper first introduces the research status and shortcomings of microstructure imaging，then summarizes the classical brain microstructure imaging methods from the perspective of signal model and multi compartment model，summarizes the advantages and disadvantages of these two types of models，and introduces the quantitative analysis methods of microstructure.Finally，the microstructure imaging technology is summarized and prospected.

微结构成像是基于扩散磁共振成像在活体内表征人脑组织微结构特性的技术，现已被广泛应用于神经科学研究和临床应用中.微结构成像模型将不同组织特性和磁共振信号相关联以估算组织的微观特性.本文首先介绍微结构成像的研究现状及不足，之后从信号模型与多隔室模型两个角度综述了经典的大脑微结构成像方法，总结这两类模型存在的优点及不足，并介绍微结构量化分析方法，最后对微结构成像技术进行总结和展望.

Diffusion-weighted imaging (DWI) provides a noninvasive tool to probe tissue microstructure. We propose a simplified model of neural cytoarchitecture intended to capture the essential features important for water diffusion as measured by NMR. Two components contribute to the NMR signal in this model: (i) the dendrites and axons, which are modeled as long cylinders with two diffusion coefficients, parallel (D(L)) and perpendicular (D(T)) to the cylindrical axis, and (ii) an isotropic monoexponential diffusion component describing water diffusion within and across all other structures, i.e., in extracellular space and glia cells. The model parameters are estimated from 153 diffusion-weighted images acquired from a formalin-fixed baboon brain. A close correspondence between the data and the signal model is found, with the model parameters consistent with literature values. The model provides an estimate of dendrite density from noninvasive MR diffusion measurements, a parameter likely to be of value for understanding normal as well as abnormal brain development and function.

Diffusional kurtosis imaging (DKI) is a clinically feasible extension of diffusion tensor imaging that probes restricted water diffusion in biological tissues using magnetic resonance imaging. Here we provide a physically meaningful interpretation of DKI metrics in white matter regions consisting of more or less parallel aligned fiber bundles by modeling the tissue as two non-exchanging compartments, the intra-axonal space and extra-axonal space. For the b-values typically used in DKI, the diffusion in each compartment is assumed to be anisotropic Gaussian and characterized by a diffusion tensor. The principal parameters of interest for the model include the intra- and extra-axonal diffusion tensors, the axonal water fraction and the tortuosity of the extra-axonal space. A key feature is that these can be determined directly from the diffusion metrics conventionally obtained with DKI. For three healthy young adults, the model parameters are estimated from the DKI metrics and shown to be consistent with literature values. In addition, as a partial validation of this DKI-based approach, we demonstrate good agreement between the DKI-derived axonal water fraction and the slow diffusion water fraction obtained from standard biexponential fitting to high b-value diffusion data. Combining the proposed WM model with DKI provides a convenient method for the clinical assessment of white matter in health and disease and could potentially provide important information on neurodegenerative disorders.Copyright © 2011 Elsevier Inc. All rights reserved.

This article presents a simple method for estimating the effective diffusion coefficients parallel and perpendicular to the axons unconfounded by the intravoxel fiber orientation distribution. We also call these parameters the per-axon or microscopic diffusion coefficients.Diffusion MR imaging is used to probe the underlying tissue material. The key observation is that for a fixed b-value the spherical mean of the diffusion signal over the gradient directions does not depend on the axon orientation distribution. By exploiting this invariance property, we propose a simple, fast, and robust estimator of the per-axon diffusion coefficients, which we refer to as the spherical mean technique.We demonstrate quantitative maps of the axon-scale diffusion process, which has factored out the effects due to fiber dispersion and crossing, in human brain white matter. These microscopic diffusion coefficients are estimated in vivo using a widely available off-the-shelf pulse sequence featuring multiple b-shells and high-angular gradient resolution.The estimation of the per-axon diffusion coefficients is essential for the accurate recovery of the fiber orientation distribution. In addition, the spherical mean technique enables us to discriminate microscopic tissue features from fiber dispersion, which potentially improves the sensitivity and/or specificity to various neurological conditions. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.© 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.

To determine the intracellular water preexchange lifetime, τ, the "average residence time" of water, in the intracellular milieu of neurons and astrocytes. The preexchange lifetime is important for modeling a variety of MR data sets, including relaxation, diffusion-sensitive, and dynamic contrast-enhanced data sets.Herein, τ in neurons and astrocytes is determined in a microbead-adherent, cultured cell system. In concert with thin-slice selection, rapid flow of extracellular media suppresses extracellular signal, allowing determination of the transcytolemmal-exchange-dominated, intracellular T. With this knowledge, and that of the intracellular T in the absence of exchange, τ can be derived.Under normal culture conditions, τ for neurons is 0.75 ± 0.05 s versus 0.57 ± 0.03 s for astrocytes. Both neuronal and astrocytic τ s decrease within 30 min after the onset of oxygen-glucose deprivation, with the astrocytic τ showing a substantially greater decrease than the neuronal τ.Given an approximate intra- to extracellular volume ratio of 4:1 in the brain, these data imply that, under normal physiological conditions, an MR experimental characteristic time of less than 0.012 s is required for a nonexchanging, two-compartment (intra- and extracellular) model to be valid for MR studies. This characteristic time shortens significantly (i.e., 0.004 s) under injury conditions. Magn Reson Med 79:1616-1627, 2018. © 2017 International Society for Magnetic Resonance in Medicine.© 2017 International Society for Magnetic Resonance in Medicine.

Spherical deconvolution methods have been applied to diffusion MRI to improve diffusion tensor tractography results in brain regions with multiple fibre crossing. Recent developments, such as the introduction of non-negative constraints on the solution, allow a more accurate estimation of fibre orientations by reducing instability effects due to noise robustness. Standard convolution methods do not, however, adequately model the effects of partial volume from isotropic tissue, such as gray matter, or cerebrospinal fluid, which may degrade spherical deconvolution results. Here we use a newly developed spherical deconvolution algorithm based on an adaptive regularization (damped version of the Richardson-Lucy algorithm) to reduce isotropic partial volume effects. Results from both simulated and in vivo datasets show that, compared to a standard non-negative constrained algorithm, the damped Richardson-Lucy algorithm reduces spurious fibre orientations and preserves angular resolution of the main fibre orientations. These findings suggest that, in some brain regions, non-negative constraints alone may not be sufficient to reduce spurious fibre orientations. Considering both the speed of processing and the scan time required, this new method has the potential for better characterizing white matter anatomy and the integrity of pathological tissue.

Diffusion-weighted (DW) MR images contain information about the orientation of brain white matter fibres that potentially can be used to study human brain connectivity in vivo using tractography techniques. Currently, the diffusion tensor model is widely used to extract fibre directions from DW-MRI data, but fails in regions containing multiple fibre orientations. The spherical deconvolution technique has recently been proposed to address this limitation. It provides an estimate of the fibre orientation distribution (FOD) by assuming the DW signal measured from any fibre bundle is adequately described by a single response function. However, the deconvolution is ill-conditioned and susceptible to noise contamination. This tends to introduce artefactual negative regions in the FOD, which are clearly physically impossible. In this study, the introduction of a constraint on such negative regions is proposed to improve the conditioning of the spherical deconvolution. This approach is shown to provide FOD estimates that are robust to noise whilst preserving angular resolution. The approach also permits the use of super-resolution, whereby more FOD parameters are estimated than were actually measured, improving the angular resolution of the results. The method provides much better defined fibre orientation estimates, and allows orientations to be resolved that are separated by smaller angles than previously possible. This should allow tractography algorithms to be designed that are able to track reliably through crossing fibre regions.

High angular resolution measurements of diffusion are used to estimate the angular distribution and diffusion anisotropy of fibers in a voxel. A simple, axially symmetric model of diffusion in white matter fibers is used to relate diffusion measurements to fiber properties. The new technique is called fiber orientation estimated using continuous axially symmetric tensors (FORECAST). It is tested using both numerical simulation and in vivo measurements. The new method agrees with other methods in voxels containing single fibers, but resolves crossing fibers better, at least at the level of diffusion weighting used in this study (tr(b) = 1480 s/mm2). The simplifying assumptions of the model are tested by comparison with the "model-free" q-ball analysis of in vivo data and the results are shown to be in good agreement. The new method addresses the problem of partial volume averaging in diffusion tensor imaging and provides a basis for more reliable estimates of fiber orientation and fractional anisotropy.(c) 2005 Wiley-Liss, Inc.

Microstructure imaging from diffusion magnetic resonance (MR) data represents an invaluable tool to study non-invasively the morphology of tissues and to provide a biological insight into their microstructural organization. In recent years, a variety of biophysical models have been proposed to associate particular patterns observed in the measured signal with specific microstructural properties of the neuronal tissue, such as axon diameter and fiber density. Despite very appealing results showing that the estimated microstructure indices agree very well with histological examinations, existing techniques require computationally very expensive non-linear procedures to fit the models to the data which, in practice, demand the use of powerful computer clusters for large-scale applications. In this work, we present a general framework for Accelerated Microstructure Imaging via Convex Optimization (AMICO) and show how to re-formulate this class of techniques as convenient linear systems which, then, can be efficiently solved using very fast algorithms. We demonstrate this linearization of the fitting problem for two specific models, i.e. ActiveAx and NODDI, providing a very attractive alternative for parameter estimation in those techniques; however, the AMICO framework is general and flexible enough to work also for the wider space of microstructure imaging methods. Results demonstrate that AMICO represents an effective means to accelerate the fit of existing techniques drastically (up to four orders of magnitude faster) while preserving accuracy and precision in the estimated model parameters (correlation above 0.9). We believe that the availability of such ultrafast algorithms will help to accelerate the spread of microstructure imaging to larger cohorts of patients and to study a wider spectrum of neurological disorders. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.