Improving fMRI Analysis and MR Reconstruction with the Incorporation of MR Relaxivities and Correlation Effect Examination

Functional magnetic resonance imaging (fMRI) and functional connectivity MRI (fcMRI) use the physical principles of nuclear MR to provide high resolution representations of brain activity and connectivity. As the fMRI and fcMRI signals are detected from the excited hydrogen atoms in a magnetic field, the acquired data is determined by the underlying physical processes, such as the MR relaxivities. In fMRI and fcMRI, the Fourier encoded frequency space measurements are reconstructed into brain images, then spatiotemporal processing operations are applied before computing the brain activation and connectivity statistics. This dissertation seeks to utilize the magnetic resonance (MR) relaxivities at different stages of the fMRI pipeline, and aims to observe the statistical implications of the spatiotemporal processing operators on the fMRI and fcMRI data. We first develop a new statistical complex-valued nonlinear fMRI activation model that incorporates the MR relaxivities of gray matter into the brain activation statistics by utilizing the physical MR magnetization equation and the first scans of the fMRI data. We provide both theoretical and experimental comparison between the proposed model with the conventional linear magnitude-only and complex-valued fMRI activation models. Our statistical analysis results show that the new model provides better accuracy in computing brain activation statistics while theoretically eliminating false positives in non-gray matter areas. We then develop a linear Fourier reconstruction operator that incorporates the MR relaxivities into the image reconstruction process to account for their effects. The utilization of a linear system makes it achievable to theoretically compute the statistical implications of the use of the proposed operator. By focusing on longitudinal relaxation time, T1, to include into the image reconstruction, we show that the application of the proposed Fourier reconstruction operator provides better image contrast in the reconstructed images by recovering the information of the tissue characteristics that exist prior to T1 equilibrium. We finally examine the effects of time series preprocessing on computed functional correlations through the use of linear operators and provide ways of accounting for such effects in computing functional activity and connectivity statistics. Using both theoretical and experimentally acquired functional connectivity data, we examine the correlations induced by commonly used spatial and temporal processing operations. Furthermore, we provide the expansion of the statistical fcMRI and fMRI models to incorporate the quantified processing induced correlations in computing brain activity and connectivity statistics

Incorporating Relaxivities to More Accurately Reconstruct MR Images

Purpose To develop a mathematical model that incorporates the magnetic resonance relaxivities into the image reconstruction process in a single step. Materials and methods In magnetic resonance imaging, the complex-valued measurements of the acquired signal at each point in frequency space are expressed as a Fourier transformation of the proton spin density weighted by Fourier encoding anomalies: T2⁎, T1, and a phase determined by magnetic field inhomogeneity (∆B) according to the MR signal equation. Such anomalies alter the expected symmetry and the signal strength of the k-space observations, resulting in images distorted by image warping, blurring, and loss in image intensity. Although T1 on tissue relaxation time provides valuable quantitative information on tissue characteristics, the T1 recovery term is typically neglected by assuming a long repetition time. In this study, the linear framework presented in the work of Rowe et al., 2007, and of Nencka et al., 2009 is extended to develop a Fourier reconstruction operation in terms of a real-valued isomorphism that incorporates the effects of T2⁎, ∆B, and T1. This framework provides a way to precisely quantify the statistical properties of the corrected image-space data by offering a linear relationship between the observed frequency space measurements and reconstructed corrected image-space measurements. The model is illustrated both on theoretical data generated by considering T2⁎, T1, and/or ∆B effects, and on experimentally acquired fMRI data by focusing on the incorporation of T1. A comparison is also made between the activation statistics computed from the reconstructed data with and without the incorporation of T1 effects. Result Accounting for T1 effects in image reconstruction is shown to recover image contrast that exists prior to T1 equilibrium. The incorporation of T1 is also shown to induce negligible correlation in reconstructed images and preserve functional activations. Conclusion With the use of the proposed method, the effects of T2⁎ and ∆B can be corrected, and T1 can be incorporated into the time series image-space data during image reconstruction in a single step. Incorporation of T1 provides improved tissue segmentation over the course of time series and therefore can improve the precision of motion correction and image registration

The SENSE-Isomorphism Theoretical Image Voxel Estimation (SENSE-ITIVE) Model for Reconstruction and Observing Statistical Properties of Reconstruction Operators

The acquisition of sub-sampled data from an array of receiver coils has become a common means of reducing data acquisition time in MRI. Of the various techniques used in parallel MRI, SENSitivity Encoding (SENSE) is one of the most common, making use of a complex-valued weighted least squares estimation to unfold the aliased images. It was recently shown in Bruce et al. [Magn. Reson. Imag. 29(2011):1267-1287] that when the SENSE model is represented in terms of a real-valued isomorphism,it assumes a skew-symmetric covariance between receiver coils, as well as an identity covariance structure between voxels. In this manuscript, we show that not only is the skew-symmetric coil covariance unlike that of real data, but the estimated covariance structure between voxels over a time series of experimental data is not an identity matrix. As such, a new model, entitled SENSE-ITIVE, is described with both revised coil and voxel covariance structures. Both the SENSE and SENSE-ITIVE models are represented in terms of real-valued isomorphisms, allowing for a statistical analysis of reconstructed voxel means, variances, and correlations resulting from the use of different coil and voxel covariance structures used in the reconstruction processes to be conducted. It is shown through both theoretical and experimental illustrations that the miss-specification of the coil and voxel covariance structures in the SENSE model results in a lower standard deviation in each voxel of the reconstructed images, and thus an artificial increase in SNR, compared to the standard deviation and SNR of the SENSE-ITIVE model where both the coil and voxel covariances are appropriately accounted for. It is also shown that there are differences in the correlations induced by the reconstruction operations of both models, and consequently there are differences in the correlations estimated throughout the course of reconstructed time series. These differences in correlations could result in meaningful differences in interpretation of results

A Statistical fMRI Model for Differential T\u3csub\u3e2\u3c/sub\u3e* Contrast Incorporating T\u3csub\u3e1\u3c/sub\u3e and T\u3csub\u3e2\u3c/sub\u3e* of Gray Matter

Relaxation parameter estimation and brain activation detection are two main areas of study in magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI). Relaxation parameters can be used to distinguish voxels containing different types of tissue whereas activation determines voxels that are associated with neuronal activity. In fMRI, the standard practice has been to discard the first scans to avoid magnetic saturation effects. However, these first images have important information on the MR relaxivities for the type of tissue contained in voxels, which could provide pathological tissue discrimination. It is also well-known that the voxels located in gray matter (GM) contain neurons that are to be active while the subject is performing a task. As such, GM MR relaxivities can be incorporated into a statistical model in order to better detect brain activation. Moreover, although the MR magnetization physically depends on tissue and imaging parameters in a nonlinear fashion, a linear model is what is conventionally used in fMRI activation studies. In this study, we develop a statistical fMRI model for Differential T2⁎ ConTrast Incorporating T1 and T2⁎ of GM, so-called DeTeCT-ING Model, that considers the physical magnetization equation to model MR magnetization; uses complex-valued time courses to estimate T1 and T2⁎ for each voxel; then incorporates gray matter MR relaxivities into the statistical model in order to better detect brain activation, all from a single pulse sequence by utilizing the first scans

A statistical examination of SENSE image reconstruction via an isomorphism representation

In magnetic resonance imaging, the parallel acquisition of subsampled spatial frequencies from an array of multiple receiver coils has become a common means of reducing data acquisition time. SENSitivity Encoding (SENSE) is a popular parallel image reconstruction model that uses a complex-valued least squares estimation process to unfold aliased images. In this article, the linear mathematical framework derived in Rowe et al. [J Neurosci Meth 159 (2007) 361–369] is built upon to perform image reconstruction with subsampled data acquired from multiple receiver coils, where the SENSE model is represented as a real-valued isomorphism. A statistical analysis is performed of the various image reconstruction operators utilized in the SENSE model, with an emphasis placed on the effects of each operator on voxel means, variances and correlations. It is shown that, despite the attractiveness of models that unfold the aliased images from subsampled data, there is an artificial correlation induced between reconstructed voxels from the different folds of aliased images. As such, the mathematical framework outlined in this manuscript could be further developed to provide a means of accounting for this unavoidable correlation induced by image reconstruction operators

Quantification of the Statistical Effects of Spatiotemporal Processing of Nontask fMRI Data

Nontask functional magnetic resonance imaging (fMRI) has become one of the most popular noninvasive areas of brain mapping research for neuroscientists. In nontask fMRI, various sources of “noise” corrupt the measured blood oxygenation level-dependent signal. Many studies have aimed to attenuate the noise in reconstructed voxel measurements through spatial and temporal processing operations. While these solutions make the data more “appealing,” many commonly used processing operations induce artificial correlations in the acquired data. As such, it becomes increasingly more difficult to derive the true underlying covariance structure once the data have been processed. As the goal of nontask fMRI studies is to determine, utilize, and analyze the true covariance structure of acquired data, such processing can lead to inaccurate and misleading conclusions drawn from the data if they are unaccounted for in the final connectivity analysis. In this article, we develop a framework that represents the spatiotemporal processing and reconstruction operations as linear operators, providing a means of precisely quantifying the correlations induced or modified by such processing rather than by performing lengthy Monte Carlo simulations. A framework of this kind allows one to appropriately model the statistical properties of the processed data, optimize the data processing pipeline, characterize excessive processing, and draw more accurate functional connectivity conclusions

Diffusion in Sephadex Gel Structures: Time Dependency Revealed by Multi-Sequence Acquisition over a Broad Diffusion Time Range

It has been increasingly reported that in biological tissues diffusion-weighted MRI signal attenuation deviates from mono-exponential decay, especially at high b-values. A number of diffusion models have been proposed to characterize this non-Gaussian diffusion behavior. One of these models is the continuous-time random-walk (CTRW) model, which introduces two new parameters: a fractional order time derivative α and a fractional order spatial derivative β. These new parameters have been linked to intravoxel diffusion heterogeneities in time and space, respectively, and are believed to depend on diffusion times. Studies on this time dependency are limited, largely because the diffusion time cannot vary over a board range in a conventional spin-echo echo-planar imaging sequence due to the accompanying T2 decays. In this study, we investigated the time-dependency of the CTRW model in Sephadex gel phantoms across a broad diffusion time range by employing oscillating-gradient spin-echo, pulsed-gradient spin-echo, and pulsed-gradient stimulated echo sequences. We also performed Monte Carlo simulations to help understand our experimental results. It was observed that the diffusion process fell into the Gaussian regime at extremely short diffusion times whereas it exhibited a strong time dependency in the CTRW parameters at longer diffusion times