The connectivity domain: Analyzing resting state fMRI data using feature-based data-driven and model-based methods.

Spontaneous fluctuations of resting state functional MRI (rsfMRI) have been widely used to understand the macro-connectome of the human brain. However, these fluctuations are not synchronized among subjects, which leads to limitations and makes utilization of first-level model-based methods challenging. Considering this limitation of rsfMRI data in the time domain, we propose to transfer the spatiotemporal information of the rsfMRI data to another domain, the connectivity domain, in which each value represents the same effect across subjects. Using a set of seed networks and a connectivity index to calculate the functional connectivity for each seed network, we transform data into the connectivity domain by generating connectivity weights for each subject. Comparison of the two domains using a data-driven method suggests several advantages in analyzing data using data-driven methods in the connectivity domain over the time domain. We also demonstrate the feasibility of applying model-based methods in the connectivity domain, which offers a new pathway for the use of first-level model-based methods on rsfMRI data. The connectivity domain, furthermore, demonstrates a unique opportunity to perform first-level feature-based data-driven and model-based analyses. The connectivity domain can be constructed from any technique that identifies sets of features that are similar across subjects and can greatly help researchers in the study of macro-connectome brain function by enabling us to perform a wide range of model-based and data-driven approaches on rsfMRI data, decreasing susceptibility of analysis techniques to parameters that are not related to brain connectivity information, and evaluating both static and dynamic functional connectivity of the brain from a new perspective.

Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4-6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that "Action" and "Cognition" are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances.

Extracting functional connectivity brain networks at the resting state from pulsed arterial spin labeling data.

Introduction: Functional connectivity in the brain is often studied with blood oxygenation level dependent (BOLD) resting state functional magnetic resonance imaging (rsfMRI), but the BOLD signal is several steps removed from neuronal activity. Arterial spin labeling (ASL), particularly pulsed ASL (PASL), has also the capacity to measure the blood-flow changes in response to activity. In this paper, we investigated the feasibility of extracting major brain networks from PASL data, in contrast with rsfMRI analsyis. Materials and methods: In this retrospective study, we analyzed a cohort dataset that consists of 21 mild traumatic brain injury (mTBI) patients and 29 healthy controls, which was collected in a previous study. By extracting 10 major brain networks from the data of both PASL and rsfMRI, we contrasted their similarities and differences in the 10 networks extracted from both modalities. Results: Our data demonstrated that PASL could be used to extract all 10 major brain networks. Eight out of 10 networks demonstrated over 60 % similarity to rsfMRI data. Meanwhile, there are similar but not identical changes in networks detected between mTBI patients and healthy controls with both modalities. Notably, the PASL-extracted default mode network (DMN), other than the rsfMRI-extracted DMN, includes some regions known to be associated with the DMN in other studies. It demonstrated that PASL data can be analyzed to identify resting state networks with reasonable reliability, even without rsfMRI data. Conclusion: Our analysis provides an opportunity to extract functional connectivity information in heritage datasets in which ASL but not BOLD was collected.

Characterization of brain microstructural abnormalities in cirrhotic patients without overt hepatic encephalopathy using diffusion kurtosis imaging.

Cirrhosis is a major public health concern. However, little is known about the neurobiological mechanisms underlying brain microstructure alterations in cirrhotic patients. The purpose of this prospective study was to investigate brain microstructural alterations in cirrhosis with or without minimal hepatic encephalopathy (MHE) and their relationship with patients' neurocognitive performance and disease duration using voxel-based analysis of diffusion kurtosis imaging (DKI). DKI data were acquired from 30 cirrhotic patients with MHE, 31 patients without MHE (NMHE) and 59 healthy controls. All DKI-derived parametric maps were compared across the three groups to investigate their group differences. Correlation analyses were further performed to assess relationships between altered imaging parameters and clinical data. Voxel-based analysis of DKI data results showed that MHE/NMHE patients had increased radial diffusivity, axial diffusivity (AD) and mean diffusivity in addition to decreased axial kurtosis (AK) and fractional anisotropy of kurtosis in several regions. Compared to controls, these regions were primarily the cingulum, temporal and frontal cortices. The DKI metrics (i.e., AK and AD) were correlated with clinical variables in the two patient groups. In conclusion, DKI is useful for detecting brain microstructural abnormalities in MHE and NMHE patients. Abnormal DKI parameters suggest alterations in brain microstructural complexity in cirrhotic patients, which may contribute to the neurobiological basis of neurocognitive impairment. These results may provide additional information on the pathophysiology of cirrhosis.

Susceptibility Weighted Imaging and Mapping of Micro-Hemorrhages and Major Deep Veins after Traumatic Brain Injury.

Micro-hemorrhages are a common result of traumatic brain injury (TBI), which can be quantified with susceptibility weighted imaging and mapping (SWIM), a quantitative susceptibility mapping approach. A total of 23 TBI patients (five women, 18 men; median age, 41.25 years old; range, 21.69-67.75 years) with an average Glasgow Coma Scale score of 7 (range, 3-15) at admission were recruited at mean 149 d (range, 57-366) after injury. Susceptibility-weighted imaging data were collected and post-processed to create SWIM images. The susceptibility value of small hemorrhages (diameter ≤10 mm) and major deep veins (right septal, left septal, central septal, right thalamostriate, left thalamostriate, internal cerebral, right basal vein of Rosenthal, left basal vein of Rosenthal, and pial veins) were evaluated. Different susceptibility thresholds were tested to determine SWIM's sensitivity and specificity for differentiating hemorrhages from the veins. A total of 253 deep veins and 173 small hemorrhages were identified and evaluated. The mean susceptibility of hemorrhages was 435±206 parts per billion (ppb) and the mean susceptibility of deep veins was 108±56 ppb. Hemorrhages showed a significantly higher susceptibility than all deep veins (p<0.001). With different thresholds (250, 227 and 200 ppb), the specificity was 97%, 95%, and 92%, and the sensitivity was 84%, 90%, and 92%, respectively. These results show that SWIM could be used to differentiate hemorrhages from veins in TBI patients in a semi-automated manner with reasonable sensitivity and specificity. A larger cohort will be needed to validate these findings.

Connectome-scale assessment of structural and functional connectivity in mild traumatic brain injury at the acute stage.

Mild traumatic brain injury (mTBI) accounts for over one million emergency visits each year in the United States. The large-scale structural and functional network connectivity changes of mTBI are still unknown. This study was designed to determine the connectome-scale brain network connectivity changes in mTBI at both structural and functional levels. 40 mTBI patients at the acute stage and 50 healthy controls were recruited. A novel approach called Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOLs) was applied for connectome-scale analysis of both diffusion tensor imaging and resting state functional MRI data. Among 358 networks identified on DICCCOL analysis, 41 networks were identified as structurally discrepant between patient and control groups. The involved major white matter tracts include the corpus callosum, and superior and inferior longitudinal fasciculi. Functional connectivity analysis identified 60 connectomic signatures that differentiate patients from controls with 93.75% sensitivity and 100% specificity. Analysis of functional domains showed decreased intra-network connectivity within the emotion network and among emotion-cognition interactions, and increased interactions among action-emotion and action-cognition as well as within perception networks. This work suggests that mTBI may result in changes of structural and functional connectivity on a connectome scale at the acute stage.

Cerebral hemodynamic changes of mild traumatic brain injury at the acute stage.

Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation.