Yimei Li

Regression models for identifying noise sources in magnetic resonance images

Stochastic noise, susceptibility artifacts, magnetic field and radiofrequency inhomogeneities, and other noise components in magnetic resonance images (MRIs) can introduce serious bias into any measurements made with those images. We formally introduce three regression models including a Rician regression model and two associated normal models to characterize stochastic noise in various magnetic resonance imaging modalities, including diffusion-weighted imaging (DWI) and functional MRI (fMRI). Estimation algorithms are introduced to maximize the likelihood function of the three regression models. We also develop a diagnostic procedure for systematically exploring MR images to identify noise components other than simple stochastic noise, and to detect discrepancies between the fitted regression models and MRI data. The diagnostic procedure includes goodness-of-fit statistics, measures of influence, and tools for graphical display. The goodness-of-fit statistics can assess the key assumptions of the three regression models, whereas measures of influence can isolate outliers caused by certain noise components, including motion artifacts. The tools for graphical display permit graphical visualization of the values for the goodness-of-fit statistic and influence measures. Finally, we conduct simulation studies to evaluate performance of these methods, and we analyze a real dataset to illustrate how our diagnostic procedure localizes subtle image artifacts by detecting intravoxel variability that is not captured by the regression models.

Asymmetrical lateral ventricular enlargement in Parkinson’s disease

Background:u2002 A recent case report suggested the presence of asymmetrical lateral ventricular enlargement associated with motor asymmetry in Parkinson’s disease (PD). The current study explored these associations further.

Intrinsic Regression Models for Positive-Definite Matrices With Applications to Diffusion Tensor Imaging.

The aim of this paper is to develop an intrinsic regression model for the analysis of positive-definite matrices as responses in a Riemannian manifold and their association with a set of covariates, such as age and gender, in a Euclidean space. The primary motivation and application of the proposed methodology is in medical imaging. Because the set of positive-definite matrices do not form a vector space, directly applying classical multivariate regression may be inadequate in establishing the relationship between positive-definite matrices and covariates of interest, such as age and gender, in real applications. Our intrinsic regression model, which is a semiparametric model, uses a link function to map from the Euclidean space of covariates to the Riemannian manifold of positive-definite matrices. We develop an estimation procedure to calculate parameter estimates and establish their limiting distributions. We develop score statistics to test linear hypotheses on unknown parameters and develop a test procedure based on a resampling method to simultaneously assess the statistical significance of linear hypotheses across a large region of interest. Simulation studies are used to demonstrate the methodology and examine the finite sample performance of the test procedure for controlling the family-wise error rate. We apply our methods to the detection of statistical significance of diagnostic effects on the integrity of white matter in a diffusion tensor study of human immunodeficiency virus. Supplemental materials for this article are available online.

Multiscale adaptive generalized estimating equations for longitudinal neuroimaging data

Many large-scale longitudinal imaging studies have been or are being widely conducted to better understand the progress of neuropsychiatric and neurodegenerative disorders and normal brain development. The goal of this article is to develop a multiscale adaptive generalized estimation equation (MAGEE) method for spatial and adaptive analysis of neuroimaging data from longitudinal studies. MAGEE is applicable to making statistical inference on regression coefficients in both balanced and unbalanced longitudinal designs and even in twin and familial studies, whereas standard software platforms have several major limitations in handling these complex studies. Specifically, conventional voxel-based analyses in these software platforms involve Gaussian smoothing imaging data and then independently fitting a statistical model at each voxel. However, the conventional smoothing methods suffer from the lack of spatial adaptivity to the shape and spatial extent of region of interest and the arbitrary choice of smoothing extent, while independently fitting statistical models across voxels does not account for the spatial properties of imaging observations and noise distribution. To address such drawbacks, we adapt a powerful propagation-separation (PS) procedure to sequentially incorporate the neighboring information of each voxel and develop a new novel strategy to solely update a set of parameters of interest, while fixing other nuisance parameters at their initial estimators. Simulation studies and real data analysis show that MAGEE significantly outperforms voxel-based analysis.

Early Changes of Tissue Perfusion After Tissue Plasminogen Activator in Hyperacute Ischemic Stroke

Background and Purpose— It is hypothesized that tissue plasminogen activator rescues brain tissue by improving perfusion. In this study, we aimed to examine acute regional perfusion changes and how they influence infarction and clinical outcome. Methods— Three sequential MR scans were performed in 15 tissue plasminogen activator-treated patients within 3.5 (tp1), at 6 hours (tp2), and at 1 month (tp3) after stroke onset. “Hypoperfusion” was defined if mean transit time prolongation was more than a threshold (4 thresholds: 3, 4, 5, and 6 seconds). Four regions of interest were classified: (1) “reperfusion”—hypoperfused at tp1, normal at tp2; (2) “nonreperfusion”—hypoperfused at tp1 and tp2; (3) “normal perfusion”—normal at tp1 and tp2; and (4) “new hypoperfusion”—normal at tp1 and hypoperfused at tp2. Risk of infarction was calculated within each region of interest. Associations between tissue perfusion changes and clinical variables were evaluated using stepwise multiple linear regressions. Moreover, the association between National Institutes of Health Stroke Scale changes and perfusion alterations was assessed using linear mixed effect models. Results— Regardless of the mean transit time threshold chosen, the risk of infarction in nonreperfused regions (40% to 68%, thresholds 3 to 6 seconds) was higher than reperfused regions (9% to 30%, P<0.05), and it was higher in new hypoperfusion regions (9% to 33%) than normal perfusion regions (3% to 4%, P<0.05). Volume of new hypoperfusion was significantly associated with onset-to-treatment time and initial hypoperfused volume. Overall relative reperfusion was significantly associated with National Institutes of Health Stroke Scale improvement. Conclusion— Early tissue perfusion changes influenced final tissue fate. The development of new hypoperfusion may result from delay in tissue plasminogen activator and a large initial lesion.

SGPP: Spatial Gaussian Predictive Process Models for Neuroimaging Data

The aim of this paper is to develop a spatial Gaussian predictive process (SGPP) framework for accurately predicting neuroimaging data by using a set of covariates of interest, such as age and diagnostic status, and an existing neuroimaging data set. To achieve a better prediction, we not only delineate spatial association between neuroimaging data and covariates, but also explicitly model spatial dependence in neuroimaging data. The SGPP model uses a functional principal component model to capture medium-to-long-range (or global) spatial dependence, while SGPP uses a multivariate simultaneous autoregressive model to capture short-range (or local) spatial dependence as well as cross-correlations of different imaging modalities. We propose a three-stage estimation procedure to simultaneously estimate varying regression coefficients across voxels and the global and local spatial dependence structures. Furthermore, we develop a predictive method to use the spatial correlations as well as the cross-correlations by employing a cokriging technique, which can be useful for the imputation of missing imaging data. Simulation studies and real data analysis are used to evaluate the prediction accuracy of SGPP and show that SGPP significantly outperforms several competing methods, such as voxel-wise linear model, in prediction. Although we focus on the morphometric variation of lateral ventricle surfaces in a clinical study of neurodevelopment, it is expected that SGPP is applicable to other imaging modalities and features.

TwinMARM: Two-Stage Multiscale Adaptive Regression Methods for Twin Neuroimaging Data

Twin imaging studies have been valuable for understanding the relative contribution of the environment and genes on brain structures and their functions. Conventional analyses of twin imaging data include three sequential steps: spatially smoothing imaging data, independently fitting a structural equation model at each voxel, and finally correcting for multiple comparisons. However, conventional analyses are limited due to the same amount of smoothing throughout the whole image, the arbitrary choice of smoothing extent, and the decreased power in detecting environmental and genetic effects introduced by smoothing raw images. The goal of this paper is to develop a two-stage multiscale adaptive regression method (TwinMARM) for spatial and adaptive analysis of twin neuroimaging and behavioral data. The first stage is to establish the relationship between twin imaging data and a set of covariates of interest, such as age and gender. The second stage is to disentangle the environmental and genetic influences on brain structures and their functions. In each stage, TwinMARM employs hierarchically nested spheres with increasing radii at each location and then captures spatial dependence among imaging observations via consecutively connected spheres across all voxels. Simulation studies show that our TwinMARM significantly outperforms conventional analyses of twin imaging data. Finally, we use our method to detect statistically significant effects of genetic and environmental variations on white matter structures in a neonatal twin study.

STGP: Spatio-temporal Gaussian process models for longitudinal neuroimaging data

Longitudinal neuroimaging data plays an important role in mapping the neural developmental profile of major neuropsychiatric and neurodegenerative disorders and normal brain. The development of such developmental maps is critical for the prevention, diagnosis, and treatment of many brain-related diseases. The aim of this paper is to develop a spatio-temporal Gaussian process (STGP) framework to accurately delineate the developmental trajectories of brain structure and function, while achieving better prediction by explicitly incorporating the spatial and temporal features of longitudinal neuroimaging data. Our STGP integrates a functional principal component model (FPCA) and a partition parametric space-time covariance model to capture the medium-to-large and small-to-medium spatio-temporal dependence structures, respectively. We develop a three-stage efficient estimation procedure as well as a predictive method based on a kriging technique. Two key novelties of STGP are that it can efficiently use a small number of parameters to capture complex non-stationary and non-separable spatio-temporal dependence structures and that it can accurately predict spatio-temporal changes. We illustrate STGP using simulated data sets and two real data analyses including longitudinal positron emission tomography data from the Alzheimers Disease Neuroimaging Initiative (ADNI) and longitudinal lateral ventricle surface data from a longitudinal study of early brain development.

Multivariate varying coefficient models for DTI tract statistics

Diffusion tensor imaging (DTI) is important for characterizing the structure of white matter fiber bundles as well as detailed tissue properties along these fiber bundles in vivo. There has been extensive interest in the analysis of diffusion properties measured along fiber tracts as a function of age, diagnostic status, and gender, while controlling for other clinical variables. However, the existing methods have several limitations including the independent analysis of diffusion properties, a lack of method for accounting for multiple covariates, and a lack of formal statistical inference, such as estimation theory and hypothesis testing. This paper presents a statistical framework, called VCMTS, to specifically address these limitations. The VCMTS framework consists of four integrated components: a varying coefficient model for characterizing the association between fiber bundle diffusion properties and a set of covariates, the local polynomial kernel method for estimating smoothed multiple diffusion properties along individual fiber bundles, global and local test statistics for testing hypotheses of interest along fiber tracts, and a resampling method for approximating the p-value of the global test statistic. The proposed methodology is applied to characterizing the development of four diffusion properties along the splenium and genu of the corpus callosum tract in a study of neurodevelopment in healthy rhesus monkeys. Significant time effects on the four diffusion properties were found.

MARM: Multiscale Adaptive Regression Models for Neuroimaging Data

We develop a novel statistical model, called multiscale adaptive regression model (MARM), for spatial and adaptive analysis of neuroimaging data. The primary motivation and application of the proposed methodology is statistical analysis of imaging data on the two-dimensional (2D) surface or in the 3D volume for various neuroimaging studies. The existing voxel-wise approach has several major limitations for the analyses of imaging data, underscoring the great need for methodological development. The voxel-wise approach essentially treats all voxels as independent units, whereas neuroimaging data are spatially correlated in nature and spatially contiguous regions of activation with rather sharp edges are usually expected. The initial smoothing step before the voxel-wise approach often blurs the image data near the edges of activated regions and thus it can dramatically increase the numbers of false positives and false negatives. The MARM, which is developed for addressing these limitations, has three key features in the analysis of imaging data: being spatial, being hierarchical, and being adaptive. The MARM builds a small sphere at each location (called voxel) and use these consecutively connected spheres across all voxels to capture spatial dependence among imaging observations. Then, the MARM builds hierarchically nested spheres by increasing the radius of a spherical neighborhood around each voxel and combine all the data in a given radius of each voxel with appropriate weights to adaptively calculate parameter estimates and test statistics. Theoretically, we first establish that the MARM outperforms classical voxel-wise approach. Simulation studies are used to demonstrate the methodology and examine the finite sample performance of the MARM. We apply our methods to the detection of spatial patterns of brain atrophy in a neuroimaging study of Alzheimers disease. Our simulation studies with known ground truth confirm that the MARM significantly outperforms the voxel-wise methods.