Data-driven optimized flip angle selection for T1 estimation from spoiled gradient echo acquisitions.

PURPOSE: Define criteria for selection of optimal flip angle sets for T1 estimation and evaluate effects on T1 mapping. THEORY AND METHODS: Flip angle sets for spoiled gradient echo-based T1 mapping were selected by minimizing T1 estimate variance weighted by the joint density of M0 and T1 in an initial acquisition. The effect of optimized flip angle selection on T1 estimate error was measured using simulations and experimental data in the human and rat brain. RESULTS: For two-point acquisitions, optimized angle sets were similar to those proposed by other groups and, therefore, performed similarly. For multipoint acquisitions, optimal angle sets for T1 mapping in the brain consisted of a repetition of two angles. Implementation of optimal angles reduced T1 estimate variance by 30-40% compared with a multipoint acquisition using a range of angles. Performance of the optimal angle set was equivalent to that of a repetition of the two-angle set selected using criteria proposed by other researchers. CONCLUSION: Repetition of two carefully selected flip angles notably improves the precision of resulting T1 estimates compared with acquisitions using a range of flip angles. This work provides a flexible and widely applicable optimization method of particular use for those who repeatedly perform T1 estimation. Magn Reson Med 76:792-802, 2016. © 2015 Wiley Periodicals, Inc.

Tract Orientation and Angular Dispersion Deviation Indicator (TOADDI): A framework for single-subject analysis in diffusion tensor imaging.

The purpose of this work is to develop a framework for single-subject analysis of diffusion tensor imaging (DTI) data. This framework is termed Tract Orientation and Angular Dispersion Deviation Indicator (TOADDI) because it is capable of testing whether an individual tract as represented by the major eigenvector of the diffusion tensor and its corresponding angular dispersion are significantly different from a group of tracts on a voxel-by-voxel basis. This work develops two complementary statistical tests based on the elliptical cone of uncertainty, which is a model of uncertainty or dispersion of the major eigenvector of the diffusion tensor. The orientation deviation test examines whether the major eigenvector from a single subject is within the average elliptical cone of uncertainty formed by a collection of elliptical cones of uncertainty. The shape deviation test is based on the two-tailed Wilcoxon-Mann-Whitney two-sample test between the normalized shape measures (area and circumference) of the elliptical cones of uncertainty of the single subject against a group of controls. The False Discovery Rate (FDR) and False Non-discovery Rate (FNR) were incorporated in the orientation deviation test. The shape deviation test uses FDR only. TOADDI was found to be numerically accurate and statistically effective. Clinical data from two Traumatic Brain Injury (TBI) patients and one non-TBI subject were tested against the data obtained from a group of 45 non-TBI controls to illustrate the application of the proposed framework in single-subject analysis. The frontal portion of the superior longitudinal fasciculus seemed to be implicated in both tests (orientation and shape) as significantly different from that of the control group. The TBI patients and the single non-TBI subject were well separated under the shape deviation test at the chosen FDR level of 0.0005. TOADDI is a simple but novel geometrically based statistical framework for analyzing DTI data. TOADDI may be found useful in single-subject, graph-theoretic and group analyses of DTI data or DTI-based tractography techniques.

4D hyperspherical harmonic (HyperSPHARM) representation of surface anatomy: a holistic treatment of multiple disconnected anatomical structures.

Image-based parcellation of the brain often leads to multiple disconnected anatomical structures, which pose significant challenges for analyses of morphological shapes. Existing shape models, such as the widely used spherical harmonic (SPHARM) representation, assume topological invariance, so are unable to simultaneously parameterize multiple disjoint structures. In such a situation, SPHARM has to be applied separately to each individual structure. We present a novel surface parameterization technique using 4D hyperspherical harmonics in representing multiple disjoint objects as a single analytic function, terming it HyperSPHARM. The underlying idea behind HyperSPHARM is to stereographically project an entire collection of disjoint 3D objects onto the 4D hypersphere and subsequently simultaneously parameterize them with the 4D hyperspherical harmonics. Hence, HyperSPHARM allows for a holistic treatment of multiple disjoint objects, unlike SPHARM. In an imaging dataset of healthy adult human brains, we apply HyperSPHARM to the hippocampi and amygdalae. The HyperSPHARM representations are employed as a data smoothing technique, while the HyperSPHARM coefficients are utilized in a support vector machine setting for object classification. HyperSPHARM yields nearly identical results as SPHARM, as will be shown in the paper. Its key advantage over SPHARM lies computationally; HyperSPHARM possess greater computational efficiency than SPHARM because it can parameterize multiple disjoint structures using much fewer basis functions and stereographic projection obviates SPHARM's burdensome surface flattening. In addition, HyperSPHARM can handle any type of topology, unlike SPHARM, whose analysis is confined to topologically invariant structures.

Optimization of a free water elimination two-compartment model for diffusion tensor imaging.

Diffusion tensor imaging is used to measure the diffusion of water in tissue. The diffusion properties carry information about the relative organization and structure of the underlying tissue. In the case of a single voxel containing both tissue and a fast diffusing component such as free water, a single diffusion tensor is no longer appropriate. A two-tensor free water elimination model has previously been proposed to correct for the case of volume mixing. Here, this model was implemented in a straightforward but novel manner without the use of spatial constraints. The optimal acquisition parameters were investigated through Monte Carlo simulations and human brain imaging studies. At a signal-to-noise ratio of 40 with 64 diffusion-weighted encoding images, the most accurate estimates of fast diffusion signal were obtained with two diffusion-weighted shells (b-value in s/mm(2)×number of directions) of 500×32 and 1500×32. The potential bias in fractional anisotropy induced by this two-compartment model was more than an order of magnitude less than the error of using the single diffusion tensor model in the presence of partial volume effects with free water. This strategy may be useful for characterizing the diffusion of tissues adjacent to cerebral spinal fluid (CSF), tissues affected by edema, and removing artifacts from blurring and ghosting of the CSF signal.

A framework for accurate determination of the T2 distribution from multiple echo magnitude MRI images.

Measurement of the T2 distribution in tissues provides biologically relevant information about normal and abnormal microstructure and organization. Typically, the T2 distribution is obtained by fitting the magnitude MR images acquired by a multi-echo MRI pulse sequence using an inverse Laplace transform (ILT) algorithm. It is well known that the ideal magnitude MR signal follows a Rician distribution. Unfortunately, studies attempting to establish the validity and efficacy of the ILT algorithm assume that these input signals are Gaussian distributed. Violation of the normality (or Gaussian) assumption introduces unexpected artifacts, including spurious cerebrospinal fluid (CSF)-like long T2 components; bias of the true geometric mean T2 values and in the relative fractions of various components; and blurring of nearby T2 peaks in the T2 distribution. Here we apply and extend our previously proposed magnitude signal transformation framework to map noisy Rician-distributed magnitude multi-echo MRI signals into Gaussian-distributed signals with high accuracy and precision. We then perform an ILT on the transformed data to obtain an accurate T2 distribution. Additionally, we demonstrate, by simulations and experiments, that this approach corrects the aforementioned artifacts in magnitude multi-echo MR images over a large range of signal-to-noise ratios.

Pseudometrically constrained centroidal voronoi tessellations: Generating uniform antipodally symmetric points on the unit sphere with a novel acceleration strategy and its applications to diffusion and three-dimensional radial MRI.

PURPOSE: The purpose of this work is to investigate the hypothesis that uniform sampling measurements that are endowed with antipodal symmetry play an important role in image quality when the raw data and image data are related through the Fourier relationship. Currently, it is extremely challenging to generate large and uniform antipodally symmetric point sets suitable for three-dimensional radial MRI. A novel approach is proposed to solve this long-standing problem in a unique and optimal way. METHODS: The proposed method is based on constrained centroidal Voronoi tessellations of the upper hemisphere with a novel pseudometric. RESULTS: The time complexity of the proposed tessellations was shown to be effectively linear, i.e., on the order of the number of sampling measurements. For small sample size, the proposed method was comparable with the state-of-the-art method (a direct iterative minimization of the electrostatic potential energy of a collection of electrons antipodal-symmetrically distributed on the unit sphere) in terms of the sampling uniformity. For large sample size, in which the state-of-the-art method is infeasible, the reconstructed images from the proposed method has less streak and ringing artifacts, when compared with those of the commonly used methods. CONCLUSION: This work proposed a unique and optimal approach to solving a long-standing problem in generating uniform sampling points for three-dimensional radial MRI.

Mean apparent propagator (MAP) MRI: a novel diffusion imaging method for mapping tissue microstructure.

Diffusion-weighted magnetic resonance (MR) signals reflect information about underlying tissue microstructure and cytoarchitecture. We propose a quantitative, efficient, and robust mathematical and physical framework for representing diffusion-weighted MR imaging (MRI) data obtained in "q-space," and the corresponding "mean apparent propagator (MAP)" describing molecular displacements in "r-space." We also define and map novel quantitative descriptors of diffusion that can be computed robustly using this MAP-MRI framework. We describe efficient analytical representation of the three-dimensional q-space MR signal in a series expansion of basis functions that accurately describes diffusion in many complex geometries. The lowest order term in this expansion contains a diffusion tensor that characterizes the Gaussian displacement distribution, equivalent to diffusion tensor MRI (DTI). Inclusion of higher order terms enables the reconstruction of the true average propagator whose projection onto the unit "displacement" sphere provides an orientational distribution function (ODF) that contains only the orientational dependence of the diffusion process. The representation characterizes novel features of diffusion anisotropy and the non-Gaussian character of the three-dimensional diffusion process. Other important measures this representation provides include the return-to-the-origin probability (RTOP), and its variants for diffusion in one- and two-dimensions-the return-to-the-plane probability (RTPP), and the return-to-the-axis probability (RTAP), respectively. These zero net displacement probabilities measure the mean compartment (pore) volume and cross-sectional area in distributions of isolated pores irrespective of the pore shape. MAP-MRI represents a new comprehensive framework to model the three-dimensional q-space signal and transform it into diffusion propagators. Experiments on an excised marmoset brain specimen demonstrate that MAP-MRI provides several novel, quantifiable parameters that capture previously obscured intrinsic features of nervous tissue microstructure. This should prove helpful for investigating the functional organization of normal and pathologic nervous tissue.

Conceptual Foundations of Diffusion in Magnetic Resonance.

A thorough review of the q-space technique is presented starting from a discussion of Fick's laws. The work presented here is primarily conceptual, theoretical and hopefully pedagogical. We offered the notion of molecular concentration to unify Fick's laws and diffusion MRI within a coherent conceptual framework. The fundamental relationship between diffusion MRI and the Fick's laws are carefully established. The conceptual and theoretical basis of the q-space technique is investigated from first principles.

Sparse and optimal acquisition design for diffusion MRI and beyond.

PURPOSE: Diffusion magnetic resonance imaging (MRI) in combination with functional MRI promises a whole new vista for scientists to investigate noninvasively the structural and functional connectivity of the human brain-the human connectome, which had heretofore been out of reach. As with other imaging modalities, diffusion MRI data are inherently noisy and its acquisition time-consuming. Further, a faithful representation of the human connectome that can serve as a predictive model requires a robust and accurate data-analytic pipeline. The focus of this paper is on one of the key segments of this pipeline-in particular, the development of a sparse and optimal acquisition (SOA) design for diffusion MRI multiple-shell acquisition and beyond. METHODS: The authors propose a novel optimality criterion for sparse multiple-shell acquisition and quasimultiple-shell designs in diffusion MRI and a novel and effective semistochastic and moderately greedy combinatorial search strategy with simulated annealing to locate the optimum design or configuration. The goal of the optimality criteria is threefold: first, to maximize uniformity of the diffusion measurements in each shell, which is equivalent to maximal incoherence in angular measurements; second, to maximize coverage of the diffusion measurements around each radial line to achieve maximal incoherence in radial measurements for multiple-shell acquisition; and finally, to ensure maximum uniformity of diffusion measurement directions in the limiting case when all the shells are coincidental as in the case of a single-shell acquisition. The approach taken in evaluating the stability of various acquisition designs is based on the condition number and the A-optimal measure of the design matrix. RESULTS: Even though the number of distinct configurations for a given set of diffusion gradient directions is very large in general-e.g., in the order of 10(232) for a set of 144 diffusion gradient directions, the proposed search strategy was found to be effective in finding the optimum configuration. It was found that the square design is the most robust (i.e., with stable condition numbers and A-optimal measures under varying experimental conditions) among many other possible designs of the same sample size. Under the same performance evaluation, the square design was found to be more robust than the widely used sampling schemes similar to that of 3D radial MRI and of diffusion spectrum imaging (DSI). CONCLUSIONS: A novel optimality criterion for sparse multiple-shell acquisition and quasimultiple-shell designs in diffusion MRI and an effective search strategy for finding the best configuration have been developed. The results are very promising, interesting, and practical for diffusion MRI acquisitions.

Temporal scaling characteristics of diffusion as a new MRI contrast: findings in rat hippocampus.

Features of the diffusion-time dependence of the diffusion-weighted magnetic resonance imaging (MRI) signal provide a new contrast that could be altered by numerous biological processes and pathologies in tissue at microscopic length scales. An anomalous diffusion model, based on the theory of Brownian motion in fractal and disordered media, is used to characterize the temporal scaling (TS) characteristics of diffusion-related quantities, such as moments of the displacement and zero-displacement probabilities, in excised rat hippocampus specimens. To reduce the effect of noise in magnitude-valued MRI data, a novel numerical procedure was employed to yield accurate estimation of these quantities even when the signal falls below the noise floor. The power-law dependencies characterize the TS behavior in all regions of the rat hippocampus, providing unique information about its microscopic architecture. The relationship between the TS characteristics and diffusion anisotropy is investigated by examining the anisotropy of TS, and conversely, the TS of anisotropy. The findings suggest the robustness of the technique as well as the reproducibility of estimates. TS characteristics of the diffusion-weighted signals could be used as a new and useful marker of tissue microstructure.

A simple scheme for generating nearly uniform distribution of antipodally symmetric points on the unit sphere.

A variant of the Thomson problem, which is about placing a set of points uniformly on the surface of a sphere, is that of generating uniformly distributed points on the sphere that are endowed with antipodal symmetry, i.e., if x is an element of the point set then -x is also an element of that point set. Point sets with antipodal symmetry are of special importance to many scientific and engineering applications. Although this type of point sets may be generated through the minimization of a slightly modified electrostatic potential, the optimization procedure becomes unwieldy when the size of the point set increases beyond a few thousands. Therefore, it is desirable to have a deterministic scheme capable of generating this type of point set with near uniformity. In this work, we will present a simple deterministic scheme to generate nearly uniform point sets with antipodal symmetry.

Extremely efficient and deterministic approach to generating optimal ordering of diffusion MRI measurements.

PURPOSE: Diffusion MRI measurements are typically acquired sequentially with unit gradient directions that are distributed uniformly on the unit sphere. The ordering of the gradient directions has significant effect on the quality of dMRI-derived quantities. Even though several methods have been proposed to generate optimal orderings of gradient directions, these methods are not widely used in clinical studies because of the two major problems. The first problem is that the existing methods for generating highly uniform and antipodally symmetric gradient directions are inefficient. The second problem is that the existing methods for generating optimal orderings of gradient directions are also highly inefficient. In this work, the authors propose two extremely efficient and deterministic methods to solve these two problems. METHODS: The method for generating nearly uniform point set on the unit sphere (with antipodal symmetry) is based upon the notion that the spacing between two consecutive points on the same latitude should be equal to the spacing between two consecutive latitudes. The method for generating optimal ordering of diffusion gradient directions is based on the idea that each subset of incremental sample size, which is derived from the prescribed and full set of gradient directions, must be as uniform as possible in terms of the modified electrostatic energy designed for antipodally symmetric point set. RESULTS: The proposed method outperformed the state-of-the-art method in terms of computational efficiency by about six orders of magnitude. CONCLUSIONS: Two extremely efficient and deterministic methods have been developed for solving the problem of optimal ordering of diffusion gradient directions. The proposed strategy is also applicable to optimal view-ordering in three-dimensional radial MRI.

NMR characterization of general compartment size distributions.

The influence of molecular diffusion on the nuclear magnetic resonance (NMR) signal can be exploited to estimate compartment size distributions in heterogeneous specimens. Theoretical relationships between the NMR signal intensity at long diffusion times and the moments of a general distribution of isolated pores with characteristic shapes (planar, cylindrical or spherical) are established. A numerical method based on expressing a general diffusion-attenuated NMR signal profile in a series of complete orthogonal basis functions is introduced and subsequently employed to estimate the moments of the compartment size distribution. The results on simulated and real data obtained from controlled water-filled microcapillaries demonstrate the power of the approach to create contrast based not only on the mean of the compartment size but also its variance. The technique can be employed to address a variety of problems such as characterizing distributions of droplet sizes in emulsions and of apparent axon diameters in nerve fascicles.

Analytically exact spiral scheme for generating uniformly distributed points on the unit sphere.

The problem of constructing a set of uniformly-distributed points on the surface of a sphere, also known as the Thomson problem, has a long and interesting history, which dates back to J.J. Thomson in 1904. A particular variant of the Thomson problem that is of great importance to biomedical imaging is that of generating a nearly uniform distribution of points on the sphere via a deterministic scheme. Although the point set generated through the minimization of electrostatic potential is the gold standard, minimizing the electrostatic potential of one thousand points (or charges) or more remains a formidable task. Therefore, a deterministic scheme capable of generating efficiently and accurately a set of uniformly-distributed points on the sphere has an important role to play in many scientific and engineering applications, not the least of which is to serve as an initial solution (with random perturbation) for the electrostatic repulsion scheme. In the work, we will present an analytically exact spiral scheme for generating a highly uniform distribution of points on the unit sphere.

Effects of physiological noise in population analysis of diffusion tensor MRI data.

The goal of this study is to characterize the potential effect of artifacts originating from physiological noise on statistical analysis of diffusion tensor MRI (DTI) data in a population. DTI derived quantities including mean diffusivity (Trace(D)), fractional anisotropy (FA), and principal eigenvector (ε(1)) are computed in the brain of 40 healthy subjects from tensors estimated using two different methods: conventional nonlinear least-squares, and robust fitting (RESTORE). RESTORE identifies artifactual data points as outliers and excludes them on a voxel-by-voxel basis. We found that outlier data points are localized in specific spatial clusters in the population, indicating a consistency in brain regions affected across subjects. In brain parenchyma RESTORE slightly reduces inter-subject variance of FA and Trace(D). The dominant effect of artifacts, however, is bias. Voxel-wise analysis indicates that inclusion of outlier data points results in clusters of under- and over-estimation of FA, while Trace(D) is always over-estimated. Removing outliers affects ε(1) mostly in low anisotropy regions. It was found that brain regions known to be affected by cardiac pulsation - cerebellum and genu of the corpus callosum, as well as regions not previously reported, splenium of the corpus callosum-show significant effects in the population analysis. It is generally assumed that statistical properties of DTI data are homogenous across the brain. This assumption does not appear to be valid based on these results. The use of RESTORE can lead to a more accurate evaluation of a population, and help reduce spurious findings that may occur due to artifacts in DTI data.

A system and mathematical framework to model shear flow effects in biomedical DW-imaging and spectroscopy.

The pulsed-field gradient (PFG) MR experiment enables one to measure particle displacements, velocities, and even higher moments of complex fluid motions. In diffusion-weighted MRI (DWI) in living tissue, where the PFG MRI experiment is used to measure diffusion, Brownian motion is assumed to dominate the displacements causing the observed signal loss. However, motions of water molecules caused by various active biological processes occurring at different length and time scales may also cause additional dephasing of magnetization and signal loss. To help understand their relative effects on the DWI signal attenuation, we used an integrated experimental and theoretical framework: a Rheo-NMR, which served as an experimental model system to precisely prescribe a microscopic velocity distribution; and a mathematical model that relates the DW signal intensity in the Rheo-NMR to experimental parameters that characterize the impressed velocity field. A technical innovation reported here is our use of 'natural' (in this case, polar) coordinates both to simplify the description the fluid motion within the Couette cell of the Rheo-NMR, as well as to acquire and reconstruct magnitude and phase MR images obtained within it. We use this integrated model system to demonstrate how shear flows appears as pseudo-diffusion in magnitude DW MR signals obtained using PFG spin-echo (PGSE) NMR and MRI sequences. Our results lead us to reinterpret the possible causes of signal loss in DWI in vivo, in particular to revise and generalize the previous notion of intra-voxel incoherent motion (IVIM) in order to describe activity driven flows that appear as pseudo-diffusion over multiple length and time scales in living tissues.

Probabilistic Identification and Estimation of Noise (PIESNO): a self-consistent approach and its applications in MRI.

Data analysis in MRI usually entails a series of processing procedures. One of these procedures is noise assessment, which in the context of this work, includes both the identification of noise-only pixels and the estimation of noise variance (standard deviation). Although noise assessment is critical to many MRI processing techniques, the identification of noise-only pixels has received less attention than has the estimation of noise variance. The main objectives of this paper are, therefore, to demonstrate (a) that the identification of noise-only pixels has an important role to play in the analysis of MRI data, (b) that the identification of noise-only pixels and the estimation of noise variance can be combined into a coherent framework, and (c) that this framework can be made self-consistent. To this end, we propose a novel iterative approach to simultaneously identify noise-only pixels and estimate the noise standard deviation from these identified pixels in a commonly used data structure in MRI. Experimental and simulated data were used to investigate the feasibility, the accuracy and the stability of the proposed technique.

Remarks on q-space MR propagator in partially restricted, axially-symmetric, and isotropic environments.

The problem of reconstruction of an apparent propagator from a series of diffusion-attenuated magnetic resonance (MR) signals is revisited. In nonimaging acquisitions, the inverse Fourier transform of the MR signal attenuation is consistent with the notion of an ensemble average propagator. However, in image acquisitions where one is interested in quantifying a displacement distribution in every voxel of the image, the propagator derived in the traditional way may lead to a counter-intuitive profile when it is nonsymmetric, which could be a problem in partially restricted environments. By exploiting the reciprocity of the diffusion propagator, an alternative is introduced, which implies a forward Fourier transform of the MR signal attenuations yielding a propagator reflected around the origin. Two simple problems were considered as examples. In the case of diffusion in the proximity of a restricting barrier, the reflected propagator yields a more meaningful result, whereas in the case of curving fibers, the original propagator is more intuitive. In the final section of the article, two more one-dimensional transformations are introduced, which enable the reconstruction of two- and three-dimensional propagators in, respectively, axially symmetric and isotropic environments - in both cases, from one-dimensional q-space MR data.

A signal transformational framework for breaking the noise floor and its applications in MRI.

A long-standing problem in magnetic resonance imaging (MRI) is the noise-induced bias in the magnitude signals. This problem is particularly pressing in diffusion MRI at high diffusion-weighting. In this paper, we present a three-stage scheme to solve this problem by transforming noisy nonCentral Chi signals to noisy Gaussian signals. A special case of nonCentral Chi distribution is the Rician distribution. In general, the Gaussian-distributed signals are of interest rather than the Gaussian-derived (e.g., Rayleigh, Rician, and nonCentral Chi) signals because the Gaussian-distributed signals are generally more amenable to statistical treatment through the principle of least squares. Monte Carlo simulations were used to validate the statistical properties of the proposed framework. This scheme opens up the possibility of investigating the low signal regime (or high diffusion-weighting regime in the case of diffusion MRI) that contains potentially important information about biophysical processes and structures of the brain.

On the six-dimensional orthogonal tensor representation of the rotation in three dimensions: A simplified approach.

The six-dimensional orthogonal tensor representation of the rotation about an axis in three dimensions was first proposed by (Mehrabadi et al. 1995). In this brief note, a simple and coherent approach is presented to construct the six-dimensional orthogonal tensor representation of the rotation of any parametrization in three dimensions and to prove its orthogonality.