Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

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

Semiparametric Bayesian models for human brain mapping

Functional magnetic resonance imaging (fMRI) has led to enormous progress in human brain mapping. Adequate analysis of the massive spatiotemporal data sets generated by this imaging technique, combining parametric and non-parametric components, imposes challenging problems in statistical modelling. Complex hierarchical Bayesian models in combination with computer-intensive Markov chain Monte Carlo inference are promising tools.The purpose of this paper is twofold. First, it provides a review of general semiparametric Bayesian models for the analysis of fMRI data. Most approaches focus on important but separate temporal or spatial aspects of the overall problem, or they proceed by stepwise procedures. Therefore, as a second aim, we suggest a complete spatiotemporal model for analysing fMRI data within a unified semiparametric Bayesian framework. An application to data from a visual stimulation experiment illustrates our approach and demonstrates its computational feasibility

Functional MRI during hippocampal deep brain stimulation in the healthy rat brain

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS

fMRI activation detection with EEG priors

The purpose of brain mapping techniques is to advance the understanding of the relationship between structure and function in the human brain in so-called activation studies. In this work, an advanced statistical model for combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings is developed to fuse complementary information about the location of neuronal activity. More precisely, a new Bayesian method is proposed for enhancing fMRI activation detection by the use of EEG-based spatial prior information in stimulus based experimental paradigms. I.e., we model and analyse stimulus influence by a spatial Bayesian variable selection scheme, and extend existing high-dimensional regression methods by incorporating prior information on binary selection indicators via a latent probit regression with either a spatially-varying or constant EEG effect. Spatially-varying effects are regularized by intrinsic Markov random field priors. Inference is based on a full Bayesian Markov Chain Monte Carlo (MCMC) approach. Whether the proposed algorithm is able to increase the sensitivity of mere fMRI models is examined in both a real-world application and a simulation study. We observed, that carefully selected EEG--prior information additionally increases sensitivity in activation regions that have been distorted by a low signal-to-noise ratio

Differential detection of impact site versus rotational site injury by magnetic resonance imaging and microglial morphology in an unrestrained mild closed head injury model.

Seventy-five percent of all traumatic brain injuries are mild and do not cause readily visible abnormalities on routine medical imaging making it difficult to predict which individuals will develop unwanted clinical sequelae. Microglia are brain-resident macrophages and early responders to brain insults. Their activation is associated with changes in morphology or expression of phenotypic markers including P2Y12 and major histocompatibility complex class II. Using a murine model of unrestrained mild closed head injury (mCHI), we used microglia as reporters of acute brain injury at sites of impact versus sites experiencing rotational stress 24&nbsp;h post-mCHI. Consistent with mild injury, a modest 20% reduction in P2Y12 expression was detected by quantitative real-time PCR (qPCR) analysis but only in the impacted region of the cortex. Furthermore, neither an influx of blood-derived immune cells nor changes in microglial expression of CD45, TREM1, TREM2, major histocompatibility complex class II or CD40 were detected. Using magnetic resonance imaging (MRI), small reductions in T2 weighted values were observed but only near the area of impact and without overt tissue damage (blood deposition, edema). Microglial morphology was quantified without cryosectioning artifacts using ScaleA(2) clarified brains from CX3CR1-green fluorescence protein (GFP) mice. The cortex rostral to the mCHI impact site receives greater rotational stress but neither MRI nor molecular markers of microglial activation showed significant changes from shams in this region. However, microglia in this rostral region did display signs of morphologic activation equivalent to that observed in severe CHI. Thus, mCHI-triggered rotational stress is sufficient to cause injuries undetectable by routine MRI that could result in altered microglial surveillance of brain homeostasis. Acute changes in microglial morphology reveal brain responses to unrestrained mild traumatic brain injury In areas subjected to rotational stress distant from impact site In the absence of detectable changes in standard molecular indicators of brain damage, inflammation or microglial activation. That might result in decreased surveillance of brain function and increased susceptibility to subsequent brain insults