核磁共振扩散测量和q-空间成像进展(英文)

在过去的近半个世纪, NMR扩散测量在理论和实践方面都不断取得进展,使得测量更加可靠和准确,并能获取越来越多的信息.随着扩散测量技术的发展,其科学应用范围也不断增加,覆盖从物理化学到临床医学等各个领域. NMR扩散测量不仅能提供分子的平移运动动力学信息,而且也可以提供影响平移运动的局部几何结构的信息,后一种应用通常称为q-空间成像.该综述聚焦于过去10年中的NMR扩散研究方面一些重大的进展.     

Dependence of temporal diffusion spectra on microstructural properties of biological tissues

The apparent diffusion coefficient (ADC) measured using magnetic resonance imaging methods provides information on microstructural properties of biological tissues, and thus has found applications as a useful biomarker for assessing changes such as those that occur in ischemic stroke and cancer. Conventional pulsed gradient spin echo methods are in widespread use and provide information on, for example, variations in cell density. The oscillating gradient spin echo (OGSE) method has the additional ability to probe diffusion behaviors more readily at short diffusion times, and the temporal diffusion spectrum obtained by the OGSE method provides a unique tool for characterizing tissues over different length scales, including structural features of intracellular spaces. It has previously been reported that several tissue properties can affect ADC measurements significantly, and the precise biophysical mechanisms that account for ADC changes in different situations are still unclear. Those factors may vary in importance depending on the time and length scale over which measurements are made. In the present work, a comprehensive numerical simulation is used to investigate the dependence of the temporal diffusion spectra measured by OGSE methods on different microstructural properties of biological tissues, including cell size, cell membrane permeability, intracellular volume fraction, intranucleus and intracytoplasm diffusion coefficients, nuclear size and T₂ relaxation times. Some unique characteristics of the OGSE method at relatively high frequencies are revealed. The results presented in the paper offer a framework for better understanding possible causes of diffusion changes and may be useful to assist the interpretation of diffusion data from OGSE measurements.     

The relationship of problems in biomedical MRI to the study of porous media.

The NMR methods that are used to characterize inanimate porous media measure relaxation times and related phenomena and material transport, fluid displacement and flow. Biological tissues are comprised of multiple small, fluid-filled compartments, such as cells, that restrict the movement of the bulk solvent water and whose constituents influence water proton relaxation times via numerous interactions with macromolecular surfaces. Several of the methods and concepts that have been developed in one field of application are also of great value in the other, and it may be expected that technical developments that have been spurred by biomedical applications of MR imaging will be used in the continuing study of porous media. Some recent specific studies from our laboratory include the development of multiple quantum coherence methods for studies of ordered water in anisotropic macromolecular assemblies, studies of the degree of restriction of water diffusion in cellular systems, multiple selective inversion imaging to depict the ratios of proton pool sizes and rates of magnetization transfer between proton populations, and diffusion tensor imaging to depict tissue anisotropies. These illustrate how approaches to obtain structural information from biological media are also relevant to porous media. For example, the recent development of oscillating gradient spin echo techniques (OGSE), an approach that extends our ability to resolve apparent diffusion changes over different time scales in tissues, has also been used to compute surface to volume measurements in assemblies of pores. Each of the new methods can be adapted to provide spatially resolved quantitative measurements of properties of interest, and these can be efficiently acquired with good accuracy using fast imaging methods such as echo planar imaging. The community of NMR scientists focused on applications to porous media should remain in close communication with those who use MRI to study problems in biomedicine, to their mutual benefits.     

Quantitative characterization of tissue microstructure with temporal diffusion spectroscopy

The signals recorded by diffusion-weighted magnetic resonance imaging (DWI) are dependent on the micro-structural properties of biological tissues, so it is possible to obtain quantitative structural information non-invasively from such measurements. Oscillating gradient spin echo (OGSE) methods have the ability to probe the behavior of water diffusion over different time scales and the potential to detect variations in intracellular structure. To assist in the interpretation of OGSE data, analytical expressions have been derived for diffusion-weighted signals with OGSE methods for restricted diffusion in some typical structures, including parallel planes, cylinders and spheres, using the theory of temporal diffusion spectroscopy. These analytical predictions have been confirmed with computer simulations. These expressions suggest how OGSE signals from biological tissues should be analyzed to characterize tissue microstructure, including how to estimate cell nuclear sizes. This approach provides a model to interpret diffusion data obtained from OGSE measurements that can be used for applications such as monitoring tumor response to treatment in vivo.     

Quantitative analysis of spatial distortions of diffusion techniques at 3T

Diffusion has been widely adopted in the clinical setting to study the microstructural tissue changes in conjunction with anatomic imaging and metabolic imaging to offer insights on the status of the tissue injury or lesion. However, geometric distortions caused by magnetic susceptibility effects, eddy currents and gradient imperfections greatly affect the clinical utility of the diffusion images. Several diffusion methods have been proposed in the recent years to obtain diffusion parameters with increased accuracy. In most cases, the comparisons to the clinical standard echo-planar imaging (EPI) diffusion are done visually without quantitative measurements. In this study, we present three simple, complementary quantitative methods of nonrigid image registration and shape analyses for evaluating spatial distortions on magnetic resonance images with application in comparing single-shot fast spin-echo (SSFSE) and EPI based diffusion measurements. These methods have confirmed the SSFSE based diffusion method is less distorted than the EPI based one, which is generally accepted through visual inspection.     

Single-shot fast spin-echo diffusion tensor imaging of the brain and spine with head and phased array coils at 1.5 T and 3.0 T

In this study, we investigated the use of a single-shot fast spin-echo-based sequence to perform diffusion tensor imaging (DTI) with improved anatomic fidelity through the entire brain and the cervical spine. Traditionally, diffusion tensor images have been acquired by single-shot echo-planar imaging (EPI) methods in which large distortions result from magnetic susceptibility effects, especially near air-tissue interfaces. These distortions can be problematic, especially in anterior and inferior portions of the brain, and they also can severely limit applications in the spine. At higher magnetic fields these magnetic susceptibility artifacts are increased. The single-shot fast spin-echo (SSFSE) method used in this study utilizes radiofrequency rephasing in the transverse plane and thus provides diffusion images with negligible distortion even at 3 Tesla. In addition, the SSFSE sequence does not require multiple fast-receivers, which are not available on many magnetic resonance (MR) systems. Phased array coils were used to increase the signal-to-noise ratio of the images, offering a major inherent advantage in diffusion tensor imaging of the spine and brain. The mean diffusion measurements obtained with the SSFSE acquisition were not statistically different (p > 0.05) from EPI-based acquisitions. Compared to routine T(2)-weighted MR images, the DTI-EPI sequence showed up to 20% in elongation of the brain in the anterior-posterior direction on a sagittal image due to magnetic susceptibility distortions, whereas in the DTI-SSFSE, the image distortions were negligible. The diffusion tensor SSFSE method was also able to assess diffusion abnormalities in a brain stem hemorrhage, unaffected by the spatial distortions that limited conventional EPI acquisition.     

Crossing fibers, diffractions and nonhomogeneous magnetic field: correction of artifacts by bipolar gradient pulses

In recent years, diffusion tensor imaging (DTI) and its variants have been used to describe fiber orientations and q-space diffusion MR was proposed as a means to obtain structural information on a micron scale. Therefore, there is an increasing need for complex phantoms with predictable microcharacteristics to challenge different indices extracted from the different diffusion MR techniques used. The present study examines the effect of diffusion pulse sequence on the signal decay and diffraction patterns observed in q-space diffusion MR performed on micron-scale phantoms of different geometries and homogeneities. We evaluated the effect of the pulse gradient stimulated-echo, the longitudinal eddy current delay (LED) and the bipolar LED (BPLED) pulse sequences. Interestingly, in the less homogeneous samples, the expected diffraction patterns were observed only when diffusion was measured with the BPLED sequence. We demonstrated the correction ability of bipolar diffusion gradients and showed that more accurate physical parameters are obtained when such a diffusion gradient scheme is used. These results suggest that bipolar gradient pulses may result in more accurate data if incorporated into conventional diffusion-weighted imaging and DTI.     

Importance of exactb-tensor calculation for quantitative diffusion tensor imaging and tracking of neuronal fiber bundles

Quantitative diffusion tensor imaging (DTI) is a novel method of magnetic resonance (MR) imaging providing information on the brain’s microstructure in vivo. DTI can be effectively measured with modern clinical MR scanners. However, imaging sequence details required for accurateb matrix calculation and for following DTI quantification are normally unknown to the user. In this work, we investigated the accuracy ofb value approximation if theb matrix is calculated without taking into account the effect of imaging gradients. It was found that an error of more than 4% in DTI estimation arises for a quite typical brain imaging protocol. The errors in mean diffusivity and fractional anisotropy index depend on diffusion tensor shape and eigenvectors orientation and exceed noise level in DTI quantification. These errors however have a strong impact on fiber tracking — up to 30% difference was found between the fiber tracks corresponding to exact and approximate calculated DTI data. Since these errors are dependent on imaging parameters and sequence implementation, accurateb matrix calculations are important for adequate comparison between data acquired on different MR scanners and also for data measured with the different imaging protocols.     

Reproducibility of MRI-derived measurements of right ventricular volumes and myocardial mass

Magnetic resonance (MR) imaging has been shown to provide accurate measurements of right ventricular (RV) volumes and myocardial mass. The purpose of this study was to evaluate the reproducibility of MR imaging, which in clinical practice may be as important as its absolute accuracy. The reproducibility of MR imaging measurements of the right ventricle was assessed by analyzing 40 serial functional MR imaging examinations of the right ventricle with variance component analysis. Standard deviations and 95% ranges for change were: for RV myocardial mass, 5.9 and 16 g; and for RV ejection fraction, 6.0% and 16%, respectively. Reproducibility was similar for cine and spin-echo MR imaging. The intraobserver and interobserver errors were especially large, indicating that observer subjectivity is the limiting factor in the interpretation of the MR images. This study suggests that the reproducibility of RV measurements is adequate to detect RV hypertrophy and a low ejection fraction in the individual patient. For accurate follow-up examinations, whereby smaller changes are to be detected, the reproducibility of MR imaging measurements may not be sufficient. More effort is needed to improve the reproducibility of MR imaging measurements.     

Reduced field-of-view DTI segmentation of cervical spine tissue

The number of diffusion tensor imaging (DTI) studies regarding the human spine has considerably increased and it is challenging because of the spine’s small size and artifacts associated with the most commonly used clinical imaging method. A novel segmentation method based on the reduced field-of-view (rFOV) DTI dataset is presented in cervical spinal canal cerebrospinal fluid, spinal cord grey matter and white matter classification in both healthy volunteers and patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Due to each channel based on high resolution rFOV DTI images providing complementary information on spinal tissue segmentation, we want to choose a different contribution map from multiple channel images. Via principal component analysis (PCA) and a hybrid diffusion filter with a continuous switch applied on fourteen channel features, eigen maps can be obtained and used for tissue segmentation based on the Bayesian discrimination method. Relative to segmentation by a pair of expert readers, all of the automated segmentation results in the experiment fall in the good segmentation area and performed well, giving an average segmentation accuracy of about 0.852 for cervical spinal cord grey matter in terms of volume overlap. Furthermore, this has important applications in defining more accurate human spinal cord tissue maps when fusing structural data with diffusion data. rFOV DTI and the proposed automatic segmentation outperform traditional manual segmentation methods in classifying MR cervical spinal images and might be potentially helpful for detecting cervical spine diseases in NMO and MS.     

Volumetric measurement of canine gliomas using MRI

The evaluation of tumor size by neurodiagnostic imaging is an important tool in determining disease progression or treatment efficacy. Apparent tumor size on any single slice image is sensitive to tumor shape and slice orientation. Volumetric measurements which use multiple, stacked images attenuate that sensitivity and can provide insights into tumor architecture. Volumetric measurements were made of induced canine gliomas using three common MR imaging protocols and with and without a contrast agent. Comparisons of the volumes described by each technique are made.     

Improvement of electrospun polymer fiber meshes pore size by femtosecond laser irradiation

Polymer meshes have recently attracted great attention due to their great variety of applications in fields such as tissue engineering and drug delivery. Poly(?-caprolactone) nanofibers were prepared by electrospinning giving rise to porous meshes. However, for some applications in tissue engineering where, for instance, cell migration into the inner regions of the mesh is aimed, the pore size obtained by conventional techniques is too narrow. To improve the pore size, laser irradiation with femtosecond pulses (i.e., negligible heat diffusion into the polymer material and confined excitation energy) is performed. A detailed study of the influence of the pulse energy, pulse length, and number of pulses on the topography of electrospun fiber meshes has been carried out, and the irradiated areas have been studied by scanning electron microscopy, contact angle measurements and spectroscopic techniques. The results show that using the optimal laser parameters, micropores are formed and the nature of the fibers is preserved.     

Effect of radiofrequency inhomogeneity on water-content based electrical properties tomography and its correction by flip angle maps

Water-content based electrical properties tomography (wEPT) can retrieve electrical properties (EPs) from water-content maps. B₁⁺ field information is not involved in the traditional magnetic resonance electrical properties tomography approach. wEPT can be performed through conventional MR scanning, such as T₁-weighted spin-echo imaging, which provides convenient access to multiple clinical applications. However, the inhomogeneous radiofrequency (RF) field induced by RF coils would cause inaccuracy in wEPT reconstructions during MR scanning. We conducted a detailed investigation to evaluate the effect of inhomogeneous RF field on wEPT reconstructions to guarantee that EP mapping is desired for clinical practice. Two important considerations are involved, namely, multiple typical coil configurations and various flip angles (FAs). We proposed a correction scheme with actual FA mapping to calibrate the RF inhomogeneity and finally validated it by using human imaging at 3 T. This study illustrates a detailed evaluation for wEPT under imperfect RF homogeneity and further provides a feasible correction procedure to mitigate it. The profound knowledge of wEPT provided in our work will benefit its performance in clinical applications.     

基于Hartley变换的磁共振成象

许多磁共振成象的应用场合需要利用正交双通道来采集一个具有时间和空间分辨力的对象序列。传统的基于Ｆｏｕｒｉｅｒ变换的成象方法，一方面，图象序列的重建时各帧图象是独立地进行重建的，因而图象序列的时间分辨力受到编码的限制；另一方面，来自两个通道之间的Ｆａｒｔｌｅｙ变换的磁共振成象技术。     

Noninvasive quantification of fluid mechanical energy losses in the total cavopulmonary connection with magnetic resonance phase velocity mapping

A major determinant of the success of surgical vascular modifications, such as the total cavopulmonary connection (TCPC), is the energetic efficiency that is assessed by calculating the mechanical energy loss of blood flow through the new connection. Currently, however, to determine the energy loss, invasive pressure measurements are necessary. Therefore, this study evaluated the feasibility of the viscous dissipation (VD) method, which has the potential to provide the energy loss without the need for invasive pressure measurements. Two experimental phantoms, a U-shaped tube and a glass TCPC, were scanned in a magnetic resonance (MR) imaging scanner and the images were used to construct computational models of both geometries. MR phase velocity mapping (PVM) acquisitions of all three spatial components of the fluid velocity were made in both phantoms and the VD was calculated. VD results from MR PVM experiments were compared with VD results from computational fluid dynamics (CFD) simulations on the image-based computational models. The results showed an overall agreement between MR PVM and CFD. There was a similar ascending tendency in the VD values as the image spatial resolution increased. The most accurate computations of the energy loss were achieved for a CFD grid density that was too high for MR to achieve under current MR system capabilities (in-plane pixel size of less than 0.4 mm). Nevertheless, the agreement between the MR PVM and the CFD VD results under the same resolution settings suggests that the VD method implemented with a clinical imaging modality such as MR has good potential to quantify the energy loss in vascular geometries such as the TCPC.     

High Probe Intensity Photobleaching Measurement of Lateral Diffusion in Cell Membranes

Lateral diffusion measurements, most commonly accomplished through Fluorescence Photobleaching Recovery (FPR or FRAP), provide important information on cell membrane molecules' size, environment and participation in intermolecular interactions. However, serious difficulties arise when these techniques are applied to weakly expressed proteins of either of two types: fusions of membrane receptors with visible fluorescent proteins or membrane molecules on autofluorescent cells. To achieve adequate sensitivity in these cases, techniques such as interference fringe FPR are needed. However, in such measurements, cytoplasmic species contribute to the fluorescence recovery signal and thus yield diffusion parameters not properly representing the small number of surface molecules. A new method helps eliminate these difficulties. High Probe Intensity (HPI)-FPR measurements retain the intrinsic confocality of spot measurements to eliminate interference from fluorescent cytoplasmic species. However, HPI-FPR methods lift the previous requirement that FPR procedures be performed at probe beam intensities low enough to not induce bleaching in samples during measurements. The high probe intensities now employed provide much larger fluorescence signals and thus more information on molecular diffusion from each measurement. We report successful measurement of membrane dynamics by this technique.     

Compressed Sensing MRI Using Sparsity Averaging and FISTA

Magnetic resonance imaging (MRI) is widely adopted for clinical diagnosis due to its non-invasively detection. However, acquisition of full k-space data limits its imaging speed. Compressed sensing (CS) provides a new technique to significantly reduce the measurements with high-quality MR image reconstruction. The sparsity of the MR images is one of the crucial bases of CS-MRI. In this paper, we present to use sparsity averaging prior for CS-MRI reconstruction in the basis of that MR images have average sparsity over multiple wavelet frames. The problem is solved using a Fast Iterative Shrinkage Thresholding Algorithm (FISTA), each iteration of which includes a shrinkage step. The performance of the proposed method is evaluated for several types of MR images. The experiment results illustrate that our approach exhibits a better performance than those methods that using redundant frame or a single orthonormal basis to promote sparsity.     

Diffusion Measurement in Phantoms and Tissues Using SLIM Localization

A new approach to efficient localized diffusion measurements has been developed and evaluated on phantoms and isolated tissues. The combination of a diffusion-sensitive pulse sequence with SLIM (spectral localization by imaging) makes efficient and accurate localized water and metabolite diffusion measurements possible with a substantial improvement in spatial or time resolution compared to standard methods. Phantom experiments showed that diffusion of substances present in relatively low concentration within small compartments can be measured accurately by this method, suggesting potential applications for diffusion measurements of metabolitesin vivo.Experiments on excised rat uterine horns demonstrated the ability of this method to measure localized diffusion of water within irregularly shaped regions of biological samples. Accurate diffusion measurements were achieved in the localized regions with acquisition times less than would have been required by standard diffusion imaging methods.     

Diffusion changes precede size reduction in neoadjuvant treatment of breast cancer

Traditionally, tumor response has been assessed via tumor size measurements during the course of a treatment. However, changes in these morphologically based measures occur relatively late in the course of a treatment. Alternative biomarkers are currently being evaluated to enable an earlier assessment of treatment to facilitate early cessation and cost savings. Diffusion-weighted imaging (DWI) has been identified by preclinical studies to be a likely alternative to tumor size measurements. In this study, 10 patients were examined prior to and after the first and second chemotherapy cycle time points. Longest diameter tumor measurements and apparent diffusion coefficients (ADCs) were recorded at each exam. An increase in the mean (normalized) ADC was noted as early as the first cycle time point. However, a reduction in the mean (normalized) longest diameter was only noted at the second cycle time point. Significant alterations from the baseline value were noted for ADC at the first (P=.005) and second cycle time points (P=.004). Longest diameter measurements only achieved a borderline significance at the second time point (P=.057). These results indicate that DWI may provide a suitable biomarker capable of providing an indication of response to treatment prior to tumor size measurements.     

扩散张量成像的人脑模板构建

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.