AM-FM Analysis of Structural and Functional Magnetic Resonance Images

This thesis proposes the application of multi-dimensional Amplitude-Modulation Frequency-Modulation (AM-FM) methods to magnetic resonance images (MRI). The basic goal is to provide a framework for exploring non-stationary characteristics of structural and functional MRI (sMRI and fMRI). First, we provide a comparison framework for the most popular AM-FM methods using different filterbank configurations that includes Gabor, Equirriple and multi-scale directional designs. We compare the performance and robustness to Gaussian noise using synthetic FM image examples. We show that the multi-dimensional quasi-local method (QLM) with an equiripple filterbank gave the best results in terms of instantaneous frequency (IF) estimation. We then apply the best performing AM-FM method to sMRI to compute the 3D IF features. We use a t-test on the IF magnitude for each voxel to find evidence of significant differences between healthy controls and patients diagnosed with schizophrenia (n=353) can be found in the IF. We also propose the use of the instantaneous phase (IP) as a new feature for analyzing fMRI images. Using principal component analysis and independent component analysis on the instantaneous phase from fMRI, we built spatial maps and identified brain regions that are biologically coherent with the task performed by the subject. This thesis provides the first application of AM-FM models to fMRI and sMRI

An Independent Component Analysis Based Tool for Exploring Functional Connections in the Brain

This thesis describes the use of independent component analysis (ICA) as a measure of voxel similarity, which allows the user to find and view statistically independent maps of correlated voxel activity. The tool developed in this work uses a specialized clustering technique, designed to find and characterize clusters of activated voxels, to compare the independent component spatial maps across patients. This same method is also used to compare SPM results across patients

Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak −48, −18, −14; ZE = 5.65, pFWEcorr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = −0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population

Multiplexed Echo Planar Imaging for Sub-Second Whole Brain FMRI and Fast Diffusion Imaging

Echo planar imaging (EPI) is an MRI technique of particular value to neuroscience, with its use for virtually all functional MRI (fMRI) and diffusion imaging of fiber connections in the human brain. EPI generates a single 2D image in a fraction of a second; however, it requires 2–3 seconds to acquire multi-slice whole brain coverage for fMRI and even longer for diffusion imaging. Here we report on a large reduction in EPI whole brain scan time at 3 and 7 Tesla, without significantly sacrificing spatial resolution, and while gaining functional sensitivity. The multiplexed-EPI (M-EPI) pulse sequence combines two forms of multiplexing: temporal multiplexing (m) utilizing simultaneous echo refocused (SIR) EPI and spatial multiplexing (n) with multibanded RF pulses (MB) to achieve m×n images in an EPI echo train instead of the normal single image. This resulted in an unprecedented reduction in EPI scan time for whole brain fMRI performed at 3 Tesla, permitting TRs of 400 ms and 800 ms compared to a more conventional 2.5 sec TR, and 2–4 times reductions in scan time for HARDI imaging of neuronal fibertracks. The simultaneous SE refocusing of SIR imaging at 7 Tesla advantageously reduced SAR by using fewer RF refocusing pulses and by shifting fat signal out of the image plane so that fat suppression pulses were not required. In preliminary studies of resting state functional networks identified through independent component analysis, the 6-fold higher sampling rate increased the peak functional sensitivity by 60%. The novel M-EPI pulse sequence resulted in a significantly increased temporal resolution for whole brain fMRI, and as such, this new methodology can be used for studying non-stationarity in networks and generally for expanding and enriching the functional information

Introduction to fMRI: experimental design and data analysis

This provides an introduction to functional MRI, experimental design and data analysis procedures using statistical parametric mapping approach

Investigating microstructural variation in the human hippocampus using non-negative matrix factorization

In this work we use non-negative matrix factorization to identify patterns of microstructural variance in the human hippocampus. We utilize high-resolution structural and diffusion magnetic resonance imaging data from the Human Connectome Project to query hippocampus microstructure on a multivariate, voxelwise basis. Application of non-negative matrix factorization identifies spatial components (clusters of voxels sharing similar covariance patterns), as well as subject weightings (individual variance across hippocampus microstructure). By assessing the stability of spatial components as well as the accuracy of factorization, we identified 4 distinct microstructural components. Furthermore, we quantified the benefit of using multiple microstructural metrics by demonstrating that using three microstructural metrics (T1-weighted/T2-weighted signal, mean diffusivity and fractional anisotropy) produced more stable spatial components than when assessing metrics individually. Finally, we related individual subject weightings to demographic and behavioural measures using a partial least squares analysis. Through this approach we identified interpretable relationships between hippocampus microstructure and demographic and behavioural measures. Taken together, our work suggests non-negative matrix factorization as a spatially specific analytical approach for neuroimaging studies and advocates for the use of multiple metrics for data-driven component analyses

Resting state functional connectivity in the default mode network and aerobic exercise in young adults

Around the world Alzheimer’s Disease (AD) is on the rise. Previous studies have shown the default mode network (DMN) sees changes with AD progression as the disease erodes away cortical areas. Aerobic exercise with significant increases to cardiorespiratory fitness could show neuro-protective changes to delay AD. This study will explore if functional connectivity changes in the DMN can be seen in a young adult sample by using group independent component analysis through FSL MELODIC. The young adult sample of 19 were selected from a larger study at the Brain Plasticity and Neuroimaging Laboratory at Boston University. The participants engaged in a twelve-week exercise intervention in either a strength training or aerobic training group. They also completed pre-intervention and post-intervention resting-state fMRI scans to evaluate change in functional connectivity in the default mode network. Cardiorespiratory fitness was assessed using a modified Balke protocol with pre-intervention and post-intervention VO2 max percentiles being used. Through two repeated-measure ANOVA analyses, this study found no significant increase in mean functional connectivity or cardiorespiratory fitness in the young adult sample. While improvements in mean VO2 max percentile and functional connectivity would have been seen with a larger sample size, this study adds to the literature by suggesting if fitness does not improve significantly, neither will functional connectivity in the default mode network