Impacts of Simultaneous Multislice Acquisition on Sensitivity and Specificity in fMRI

Simultaneous multislice (SMS) imaging can be used to decrease the time between acquisition of fMRI volumes, which can increase sensitivity by facilitating the removal of higher-frequency artifacts and boosting effective sample size. The technique requires an additional processing step in which the slices are separated, or unaliased, to recover the whole brain volume. However, this may result in signal “leakage” between aliased locations, i.e., slice “leakage,” and lead to spurious activation (decreased specificity). SMS can also lead to noise amplification, which can reduce the benefits of decreased repetition time. In this study, we evaluate the original slice-GRAPPA (no leak block) reconstruction algorithmand acceleration factor (AF = 8) used in the fMRI data in the young adult Human Connectome Project (HCP). We also evaluate split slice-GRAPPA (leak block), which can reduce slice leakage. We use simulations to disentangle higher test statistics into true positives (sensitivity) and false positives (decreased specificity). Slice leakage was greatly decreased by split slice-GRAPPA. Noise amplification was decreased by using moderate acceleration factors (AF = 4). We examined slice leakage in unprocessed fMRI motor task data from the HCP. When data were smoothed, we found evidence of slice leakage in some, but not all, subjects. We also found evidence of SMS noise amplification in unprocessed task and processed resting-state HCP data

EEG-informed fMRI reveals spatiotemporal characteristics of perceptual decision making

Single-unit and multiunit recordings in primates have already established that decision making involves at least two general stages of neural processing: representation of evidence from early sensory areas and accumulation of evidence to a decision threshold from decision-related regions. However, the relay of information from early sensory to decision areas, such that the accumulation process is instigated, is not well understood. Using a cued paradigm and single-trial analysis of electroencephalography (EEG), we previously reported on temporally specific components related to perceptual decision making. Here, we use information derived from our previous EEG recordings to inform the analysis of fMRI data collected for the same behavioral task to ascertain the cortical origins of each of these EEG components. We demonstrate that a cascade of events associated with perceptual decision making takes place in a highly distributed neural network. Of particular importance is an activation in the lateral occipital complex implicating perceptual persistence as a mechanism by which object decision making in the human brain is instigated

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

Real-time decoding of question-and-answer speech dialogue using human cortical activity.

Natural communication often occurs in dialogue, differentially engaging auditory and sensorimotor brain regions during listening and speaking. However, previous attempts to decode speech directly from the human brain typically consider listening or speaking tasks in isolation. Here, human participants listened to questions and responded aloud with answers while we used high-density electrocorticography (ECoG) recordings to detect when they heard or said an utterance and to then decode the utterance's identity. Because certain answers were only plausible responses to certain questions, we could dynamically update the prior probabilities of each answer using the decoded question likelihoods as context. We decode produced and perceived utterances with accuracy rates as high as 61% and 76%, respectively (chance is 7% and 20%). Contextual integration of decoded question likelihoods significantly improves answer decoding. These results demonstrate real-time decoding of speech in an interactive, conversational setting, which has important implications for patients who are unable to communicate

Spatio-temporal wavelet regularization for parallel MRI reconstruction: application to functional MRI

Parallel MRI is a fast imaging technique that enables the acquisition of highly resolved images in space or/and in time. The performance of parallel imaging strongly depends on the reconstruction algorithm, which can proceed either in the original k-space (GRAPPA, SMASH) or in the image domain (SENSE-like methods). To improve the performance of the widely used SENSE algorithm, 2D- or slice-specific regularization in the wavelet domain has been deeply investigated. In this paper, we extend this approach using 3D-wavelet representations in order to handle all slices together and address reconstruction artifacts which propagate across adjacent slices. The gain induced by such extension (3D-Unconstrained Wavelet Regularized -SENSE: 3D-UWR-SENSE) is validated on anatomical image reconstruction where no temporal acquisition is considered. Another important extension accounts for temporal correlations that exist between successive scans in functional MRI (fMRI). In addition to the case of 2D+t acquisition schemes addressed by some other methods like kt-FOCUSS, our approach allows us to deal with 3D+t acquisition schemes which are widely used in neuroimaging. The resulting 3D-UWR-SENSE and 4D-UWR-SENSE reconstruction schemes are fully unsupervised in the sense that all regularization parameters are estimated in the maximum likelihood sense on a reference scan. The gain induced by such extensions is illustrated on both anatomical and functional image reconstruction, and also measured in terms of statistical sensitivity for the 4D-UWR-SENSE approach during a fast event-related fMRI protocol. Our 4D-UWR-SENSE algorithm outperforms the SENSE reconstruction at the subject and group levels (15 subjects) for different contrasts of interest (eg, motor or computation tasks) and using different parallel acceleration factors (R=2 and R=4) on 2x2x3mm3 EPI images.Comment: arXiv admin note: substantial text overlap with arXiv:1103.353

Role of noninvasive molecular imaging in determining response

The intersection of immunotherapy and radiation oncology is a rapidly evolving area of preclinical and clinical investigation. The strategy of combining radiation and immunotherapy to enhance local and systemic antitumor immune responses is intriguing yet largely unproven in the clinical setting because the mechanisms of synergy and the determinants of therapeutic response remain undefined. In recent years, several noninvasive molecular imaging approaches have emerged as a platform to interrogate the tumor immune microenvironment. These tools have the potential to serve as robust biomarkers for cancer immunotherapy and may hold several advantages over conventional anatomic imaging modalities and contemporary invasive tissue acquisition techniques. Given the key and expanding role of precision imaging in radiation oncology for patient selection, target delineation, image guided treatment delivery, and response assessment, noninvasive molecular-specific imaging may be uniquely suited to evaluate radiation/immunotherapy combinations. Herein, we describe several experimental imaging-based strategies that are currently being explored to characterize in vivo immune responses, and we review a growing body of preclinical data and nascent clinical experience with immuno-positron emission tomography molecular imaging as a putative biomarker for cancer immunotherapy. Finally, we discuss practical considerations for clinical translation to implement noninvasive molecular imaging of immune checkpoint molecules, immune cells, or associated elements of the antitumor immune response with a specific emphasis on its potential application at the interface of radiation oncology and immuno-oncology

Partially Adaptive STAP Algorithm Approaches to Functional MRI

In this work, the architectures of three partially adaptive STAP algorithms are introduced, one of which is explored in detail, that reduce dimensionality and improve tractability over fully adaptive STAP when used in construction of brain activation maps in fMRI. Computer simulations incorporating actual MRI noise and human data analysis indicate that element space partially adaptive STAP can attain close to the performance of fully adaptive STAP while significantly decreasing processing time and maximum memory requirements, and thus demonstrates potential in fMRI analysis

Complex-valued Time Series Modeling for Improved Activation Detection in fMRI Studies

A complex-valued data-based model with th order autoregressive errors and general real/imaginary error covariance structure is proposed as an alternative to the commonly used magnitude-only data-based autoregressive model for fMRI time series. Likelihood-ratio-test-based activation statistics are derived for both models and compared for experimental and simulated data. For a dataset from a right-hand finger-tapping experiment, the activation map obtained using complex-valued modeling more clearly identifies the primary activation region (left functional central sulcus) than the magnitude-only model. Such improved accuracy in mapping the left functional central sulcus has important implications in neurosurgical planning for tumor and epilepsy patients. Additionally, we develop magnitude and phase detrending procedures for complex-valued time series and examine the effect of spatial smoothing. These methods improve the power of complex-valued data-based activation statistics. Our results advocate for the use of the complex-valued data and the modeling of its dependence structures as a more efficient and reliable tool in fMRI experiments over the current practice of using only magnitude-valued datasets

Spatiotemporal dynamics of low frequency fluctuations in bold fMRI

Traditional fMRI utilizes blood oxygenation level dependent (BOLD) contrast to map brain activity. BOLD signal is sensitive to the hemodynamic changes associated with brain activity, and gives an indirect measure of brain activity. Low frequency fluctuations (LFFs) have been observed in the BOLD signal even in the absence of any anesthetic agent, and the correlations between the fluctuations from different brain regions has been used to map functional connectivity in the brain. Most studies involving spontaneous fluctuations in the BOLD signal extract connectivity patterns that show relationships between brain areas that are maintained over the length of the scanning session. The research presented in this document investigates the spatiotemporal dynamics of the BOLD fluctuations to identify common spatiotemporal patterns within a scan. First, the presence of a visually detectable spatiotemporal propagation pattern is demonstrated by utilizing single-slice data with high spatial and temporal resolution. The pattern consists of lateral-medial propagation of BOLD signal, demonstrating the presence of time-varying features in spontaneous BOLD fluctuations. Further, a novel pattern finding algorithm is developed for detecting repeated spatiotemporal patterns in BOLD fMRI data. The algorithm is applied to high temporal resolution T2*-weighted multislice images obtained from rats and humans in the absence of any task or stimulation. In rats, the primary pattern consists of waves of high signal intensity, propagating in a lateral-medial direction across the cortex, replicating the results obtained using visual observation. In humans, the most common spatiotemporal pattern consisted of an alteration between activation of areas comprising the "default-mode" (e.g., posterior cingulate and anterior medial prefrontal cortices) and the "task-positive" (e.g., superior parietal and premotor cortices) networks. Signal propagation from focal starting points is also observed. The pattern finding algorithm is shown to be reasonably insensitive to the variation in user-defined parameters, and the results are consistent within and between subjects. This novel approach for probing the spontaneous network activity of the brain has implications for the interpretation of conventional functional connectivity studies, and may increase the amount of information that can be obtained from neuroimaging data.Ph.D.Committee Chair: Keilholz, Shella; Committee Member: Hu, Xiaoping; Committee Member: Jaeger, Dieter; Committee Member: Sathian, Krish; Committee Member: Schumacher, Eri

A spatiotemporal nonparametric Bayesian model of multi-subject fMRI data

In this paper we propose a unified, probabilistically coherent framework for the analysis of task-related brain activity in multi-subject fMRI experiments. This is distinct from two-stage “group analysis” approaches traditionally considered in the fMRI literature, which separate the inference on the individual fMRI time courses from the inference at the population level. In our modeling approach we consider a spatiotemporal linear regression model and specifically account for the between-subjects heterogeneity in neuronal activity via a spatially informed multi-subject nonparametric variable selection prior. For posterior inference, in addition to Markov chain Monte Carlo sampling algorithms, we develop suitable variational Bayes algorithms. We show on simulated data that variational Bayes inference achieves satisfactory results at more reduced computational costs than using MCMC, allowing scalability of our methods. In an application to data collected to assess brain responses to emotional stimuli our method correctly detects activation in visual areas when visual stimuli are presented