Interhemispheric Connectivity of the Human Temporal Lobes.

Much is known regarding the major white matter pathways connecting the right and left temporal lobes, which project through the posterior corpus callosum, the anterior commissure, and the dorsal hippocampal commissure. However, details about the spatial location of these tracts are unclear, including their exact course and proximity to cortical and subcortical structures, the spatial relations between corpus callosum and anterior commissure projections, and the caudal extent of transcallosal connections within the splenium. We present an atlas of these tracts derived from high angular resolution diffusion tractography maps, providing improved visualization of the spatial relationships of these tracts. The data show several new details, including branching of the transcallosal pathway into medial and lateral divisions, projections of the transcallosal pathway into the external capsule and claustrum, complex patterns of overlap and interdigitation of the transcallosal and anterior commissure tracts, distinct dorsal and ventral regions of the splenium with high tract densities, and absence of temporal lobe projections in the caudal third of the splenium. Intersection of individual tract probability maps with individual cortical surfaces were used to identify likely regions with relatively higher cortical termination densities. These data should be useful for planning surgical approaches involving the temporal lobe and for developing functional-anatomical models of processes that depend on interhemispheric temporal lobe integration, including speech perception, semantic memory, and social cognition. Highlights: Interhemispheric connections of the human temporal lobes were visualized using high angular resolution diffusion tensor imaging tractography.Results are displayed on serial orthogonal sections to reveal detailed spatial relationships.Corpus callosum projections through the splenium form distinct dorsal and ventral bundles and are absent from the caudal splenium.The transcallosal pathway consists of distinct medial and lateral divisions.The results reveal projections to the external capsule and claustrum not previously described.Transcallosal and anterior commissural pathways show complex patterns of overlap and interdigitation.Surface mapping revealed areas with relatively high density of projections to the cortical surface.

Associations of prior concussion severity with brain microstructure using mean apparent propagator magnetic resonance imaging.

Magnetic resonance imaging (MRI) diffusion studies have shown chronic microstructural tissue abnormalities in athletes with history of concussion, but with inconsistent findings. Concussions with post-traumatic amnesia (PTA) and/or loss of consciousness (LOC) have been connected to greater physiological injury. The novel mean apparent propagator (MAP) MRI is expected to be more sensitive to such tissue injury than the conventional diffusion tensor imaging. This study examined effects of prior concussion severity on microstructure with MAP-MRI. Collegiate-aged athletes (N = 111, 38 females; ≥6 months since most recent concussion, if present) completed semistructured interviews to determine the presence of prior concussion and associated injury characteristics, including PTA and LOC. MAP-MRI metrics (mean non-Gaussian diffusion [NG Mean], return-to-origin probability [RTOP], and mean square displacement [MSD]) were calculated from multi-shell diffusion data, then evaluated for associations with concussion severity through group comparisons in a primary model (athletes with/without prior concussion) and two secondary models (athletes with/without prior concussion with PTA and/or LOC, and athletes with/without prior concussion with LOC only). Bayesian multilevel modeling estimated models in regions of interest (ROI) in white matter and subcortical gray matter, separately. In gray matter, the primary model showed decreased NG Mean and RTOP in the bilateral pallidum and decreased NG Mean in the left putamen with prior concussion. In white matter, lower NG Mean with prior concussion was present in all ROI across all models and was further decreased with LOC. However, only prior concussion with LOC was associated with decreased RTOP and increased MSD across ROI. Exploratory analyses conducted separately in male and female athletes indicate associations in the primary model may differ by sex. Results suggest microstructural measures in gray matter are associated with a general history of concussion, while a severity-dependent association of prior concussion may exist in white matter.

Characterization of diffusion MRI using the mean apparent propagator model in hemodialysis patients: A pilot study.

To better understand documented cognitive decline in hemodialysis (HD) patients, diffusion MRI (dMRI) has been used to characterize brain anatomical deficits relative to controls. Studies to this point have primarily used diffusion tensor imaging (DTI) to model the three-dimensional diffusion of water in HD patients, with DTI parameters reflecting underlying microstructural changes of brain tissue. Since DTI has some limitations in characterizing tissue microstructure, some of which may be complicated by HD, we explored the use of the mean apparent propagator (MAP) model to describe diffusion in HD patients. We collected anatomical T1 and T2 FLAIR MRIs as well as multi-shell dMRI in ten HD participants and ten age-matched controls. The T1 and T2 FLAIR MRIs were used for tissue segmentation and identification of white matter hyperintensity, respectively. Multi-shell dMRI data were used to estimate MAP and DTI diffusion models. Each model was then used to characterize the differences between the HD cohort and the age-matched controls in normal appearing white matter, subcortical gray matter, corpus callosum (CC) and bilateral radiata (Rad). As expected, parameters of both DTI and MAP models of dMRI were significantly different in HD participants compared to controls. However, some MAP parameters suggested additional tissue microstructural changes in HD participants, such as increased axonal diameter. Measurements of non-Gaussianity indicated that MAP provided better a diffusion estimate than DTI, and MAP appeared to provide a more accurate measure of anisotropy in Rad, based on measures of the Rad/CC ratio. In conclusion, parameters of the MAP and DTI models were both sensitive to changes in diffusivity in HD participants compared to controls; however, the MAP model appeared to provide additional detailed information about changes in brain tissue microstructure.

Dynamic tracking of scaphoid, lunate, and capitate carpal bones using four-dimensional MRI.

A preliminary exploration of technical methodology for dynamic analysis of scaphoid, capitate, and lunate during unconstrained movements is performed in this study. A heavily accelerated and fat-saturated 3D Cartesian MRI acquisition was used to capture temporal frames of the unconstrained moving wrist of 5 healthy subjects. A slab-to-volume point-cloud based registration was then utilized to register the moving volumes to a high-resolution image volume collected at a neutral resting position. Comprehensive in-silico error analyses for different acquisition parameter settings were performed to evaluate the performance limits of several dynamic metrics derived from the registration parameters. Computational analysis suggested that sufficient volume coverage for the dynamic acquisitions was reached when collecting 12 slice-encodes at 2.5mm resolution, which yielded a temporal resolution of and 2.6 seconds per volumetric frame. These acquisition parameters resulted in total in-silico errors of 1.9°±1.8° and 3°±4.6° in derived principal rotation angles within ulnar-radial deviation and flexion-extension motion, respectively. Rotation components of the carpal bones in the radius coordinate system were calculated and found to be consistent with earlier 4D-CT studies. Temporal metric profiles derived from ulnar-radial deviation motion demonstrated better performance than those derived from flexion/extension movements. Future work will continue to explore the use of these methods in deriving more complex dynamic metrics and their application to subjects with symptomatic carpal dysfunction.

Diffusion propagator metrics are biased when simultaneous multi-slice acceleration is used.

Advanced diffusion MRI models are being explored to study the complex microstructure of the brain with higher accuracy. However, these techniques require long acquisition times. Simultaneous Multi-Slice (SMS) accelerates data acquisition by exciting multiple image slices simultaneously and separating the overlapping slices using a mathematical model, which makes use of the distinct information coming from an array of receive coils. However, SMS acceleration introduces increased noise in reconstructed images and crosstalk between simultaneously excited slices. These compounded effects from SMS acceleration could affect quantitative MRI techniques such as diffusion imaging. In this study, the effects of SMS acceleration on the accuracy of propagator metrics obtained from a model-free advanced diffusion technique called Mean Apparent Propagator MRI (MAP-MRI) was investigated. Ten healthy volunteers were scanned with SMS accelerated multi-shell diffusion MRI acquisitions. Group analyses were performed to study brain regions affected by SMS acceleration. In addition, diffusion metrics from atlas-based fiber tracts of interest were analyzed to investigate how propagator metrics in major fiber tracts were biased by 2- and 3-band SMS acceleration. Both zero-displacement metrics and non-Gaussianity metrics were significantly altered when SMS acceleration was used. MAP-MRI metrics calculated from SMS-3 showed significant differences with respect to SMS-2. Furthermore, with the shorter TR afforded by SMS acceleration, the characteristics of this bias have changed. This has implications for studies using diffusion MRI with SMS acceleration to investigate the effects of a disease or injury on the brain tissues.

Value CMR: Towards a Comprehensive, Rapid, Cost-Effective Cardiovascular Magnetic Resonance Imaging.

Cardiac magnetic resonance imaging (CMR) is considered the gold standard for measuring cardiac function. Further, in a single CMR exam, information about cardiac structure, tissue composition, and blood flow could be obtained. Nevertheless, CMR is underutilized due to long scanning times, the need for multiple breath-holds, use of a contrast agent, and relatively high cost. In this work, we propose a rapid, comprehensive, contrast-free CMR exam that does not require repeated breath-holds, based on recent developments in imaging sequences. Time-consuming conventional sequences have been replaced by advanced sequences in the proposed CMR exam. Specifically, conventional 2D cine and phase-contrast (PC) sequences have been replaced by optimized 3D-cine and 4D-flow sequences, respectively. Furthermore, conventional myocardial tagging has been replaced by fast strain-encoding (SENC) imaging. Finally, T1 and T2 mapping sequences are included in the proposed exam, which allows for myocardial tissue characterization. The proposed rapid exam has been tested in vivo. The proposed exam reduced the scan time from >1 hour with conventional sequences to <20 minutes. Corresponding cardiovascular measurements from the proposed rapid CMR exam showed good agreement with those from conventional sequences and showed that they can differentiate between healthy volunteers and patients. Compared to 2D cine imaging that requires 12-16 separate breath-holds, the implemented 3D-cine sequence allows for whole heart coverage in 1-2 breath-holds. The 4D-flow sequence allows for whole-chest coverage in less than 10 minutes. Finally, SENC imaging reduces scan time to only one slice per heartbeat. In conclusion, the proposed rapid, contrast-free, and comprehensive cardiovascular exam does not require repeated breath-holds or to be supervised by a cardiac imager. These improvements make it tolerable by patients and would help improve cost effectiveness of CMR and increase its adoption in clinical practice.

Association of Head Impact Exposure with White Matter Macrostructure and Microstructure Metrics.

Prior studies have reported white matter abnormalities associated with a history of cumulative concussion and/or repetitive head impacts (RHI) in contact sport athletes. Growing evidence suggests these abnormalities may begin as more subtle changes earlier in life in active younger athletes. We investigated the relationship between prior concussion and contact sport exposure with multi-modal white matter microstructure and macrostructure using magnetic resonance imaging. High school and collegiate athletes (n = 121) completed up to four evaluations involving neuroimaging. Linear mixed-effects models examined associations of years of contact sport exposure (i.e., RHI proxy) and prior concussion across multiple metrics of white matter, including total white matter volume, diffusion tensor imaging (DTI) metrics, diffusion kurtosis imaging (DKI) metrics, and quantitative susceptibility mapping (QSM). A significant inverse association between cumulative years of contact sport exposure and QSM was observed, F(1, 237.77) = 4.67, p = 0.032. Cumulative contact sport exposure was also associated with decreased radial diffusivity, F(1, 114.56) = 5.81, p = 0.018, as well as elevated fractional anisotropy, F(1, 115.32) = 5.40, p = 0.022, and radial kurtosis, F(1, 113.45) = 4.03, p = 0.047. In contrast, macroscopic white matter volume was not significantly associated with cumulative contact sport exposure (p > 0.05). Concussion history was not significantly associated with QSM, DTI, DKI, or white matter volume (all, p > 0.05). Cumulative contact sport exposure is associated with subtle differences in white matter microstructure, but not gross white matter macrostructure, in young active athletes. Longitudinal follow-up is required to assess the progression of these findings to determine their contribution to potential adverse effects later in life.

Split-slice training and hyperparameter tuning of RAKI networks for simultaneous multi-slice reconstruction.

PURPOSE: Simultaneous multi-slice acquisitions are essential for modern neuroimaging research, enabling high temporal resolution functional and high-resolution q-space sampling diffusion acquisitions. Recently, deep learning reconstruction techniques have been introduced for unaliasing these accelerated acquisitions, and robust artificial-neural-networks for k-space interpolation (RAKI) have shown promising capabilities. This study systematically examines the impacts of hyperparameter selections for RAKI networks, and introduces a novel technique for training data generation which is analogous to the split-slice formalism used in slice-GRAPPA. METHODS: RAKI networks were developed with variable hyperparameters and with and without split-slice training data generation. Each network was trained and applied to five different datasets including acquisitions harmonized with Human Connectome Project lifespan protocol. Unaliasing performance was assessed through L1 errors computed between unaliased and calibration frequency-space data. RESULTS: Split-slice training significantly improved network performance in nearly all hyperparameter configurations. Best unaliasing results were achieved with three layer RAKI networks using at least 64 convolutional filters with receptive fields of 7 voxels, 128 single-voxel filters in the penultimate RAKI layer, batch normalization, and no training dropout with the split-slice augmented training dataset. Networks trained without the split-slice technique showed symptoms of network over-fitting. CONCLUSIONS: Split-slice training for simultaneous multi-slice RAKI networks positively impacts network performance. Hyperparameter tuning of such reconstruction networks can lead to further improvements in unaliasing performance.

Cardiac functional magnetic resonance imaging at 7T: Image quality optimization and ultra-high field capabilities.

BACKGROUND: 7T cardiac magnetic resonance imaging (MRI) introduces several advantages, as well as some limitations, compared to lower-field imaging. The capabilities of ultra-high field (UHF) MRI have not been fully exploited in cardiac functional imaging. AIM: To optimize 7T cardiac MRI functional imaging without the need for conducting B1 shimming or subject-specific tuning, which improves scan efficiency. In this study, we provide results from phantom and in vivo scans using a multi-channel transceiver modular coil. METHODS: We investigated the effects of adding a dielectric pad at different locations next to the imaged region of interest on improving image quality in subjects with different body habitus. We also investigated the effects of adjusting the imaging flip angle in cine and tagging sequences on improving image quality, B1 field homogeneity, signal-to-noise ratio (SNR), blood-myocardium contrast-to-noise ratio (CNR), and tagging persistence throughout the cardiac cycle. RESULTS: The results showed the capability of achieving improved image quality with high spatial resolution (0.75 mm × 0.75 mm × 2 mm), high temporal resolution (20 ms), and increased tagging persistence (for up to 1200 ms cardiac cycle duration) at 7T cardiac MRI after adjusting scan set-up and imaging parameters. Adjusting the imaging flip angle was essential for achieving optimal SNR and myocardium-to-blood CNR. Placing a dielectric pad at the anterior left position of the chest resulted in improved B1 homogeneity compared to other positions, especially in subjects with small chest size. CONCLUSION: Improved regional and global cardiac functional imaging can be achieved at 7T MRI through simple scan set-up adjustment and imaging parameter optimization, which would allow for more streamlined and efficient UHF cardiac MRI.

Optimization of hyperparameters for SMS reconstruction.

PURPOSE: Simultaneous multi-slice (SMS) imaging accelerates MRI data acquisition by exciting multiple image slices with a single radiofrequency pulse. Overlapping slices encoded in acquired signal are separated using a mathematical model, which requires estimation of image reconstruction kernels using calibration data. Several parameters used in SMS reconstruction impact the quality and fidelity of final images. Therefore, finding an optimal set of reconstruction parameters is critical to ensure that accelerated acquisition does not significantly degrade resulting image quality. METHODS: Gradient-echo echo planar imaging data were acquired with a range of SMS acceleration factors from a cohort of five volunteers with no known neurological pathology. Images were collected using two available phased-array head coils (a 48-channel array and a reduced diameter 32-channel array) that support SMS. Data from these coils were identically reconstructed offline using a range of coil compression factors and reconstruction kernel parameters. A hybrid space (k-x), externally-calibrated coil-by-coil slice unaliasing approach was used for image reconstruction. The image quality of the resulting reconstructed SMS images was assessed by evaluating correlations with identical echo-planar reference data acquired without SMS. A finger tapping functional MRI (fMRI) experiment was also performed and group analysis results were compared between data sets reconstructed with different coil compression levels. RESULTS: Between the two RF coils tested in this study, the 32-channel coil with smaller dimensions clearly outperformed the larger 48-channel coil in our experiments. Generally, a large calibration region (144-192 samples) and small kernel sizes (2-4 samples) in ky direction improved image quality. Use of regularization in the kernel fitting procedure had a notable impact on the fidelity of reconstructed images and a regularization value 0.0001 provided good image quality. With optimal selection of other hyperparameters in the hybrid space SMS unaliasing algorithm, coil compression caused small reduction in correlation between single-band and SMS unaliased images. Similarly, group analysis of fMRI results did not show a significant influence of coil compression on resulting image quality. CONCLUSIONS: This study demonstrated that the hyperparameters used in SMS reconstruction need to be fine-tuned once the experimental factors such as the RF receive coil and SMS factor have been determined. A cursory evaluation of SMS reconstruction hyperparameter values is therefore recommended before conducting a full-scale quantitative study using SMS technologies.

Serial Diffusion Kurtosis Magnetic Resonance Imaging Study during Acute, Subacute, and Recovery Periods after Sport-Related Concussion.

Sport-related concussion (SRC) is common in contact sports, but there remains a lack of reliable, unbiased biomarkers of brain injury and recovery. Although the symptoms of SRC generally resolve over a period of days to weeks, the lack of a biomarker impairs detection and return-to-play decisions. To this date, the pathophysiological recovery profile and relationships between brain changes and symptoms remained unclear. In the current study, diffusion kurtosis imaging (DKI) was used to monitor the effects of SRC on the brain and the trajectory of recovery in concussed American football players (n = 96) at <48 h, and 8, 15, and 45 days post-injury, who were compared with a matched group of uninjured players (n = 82). The concussed group reported significantly higher symptoms within 48 h after injury than controls, which resolved by the 8-day follow-up. The concussed group also demonstrated poorer performance on balance testing at <48 h and 8 days than controls. There were no significant differences between the groups in the Standardized Assessment of Concussion (SAC), a cognitive screening measure. DKI data were acquired with 3 mm isotropic resolution, and analyzed using tract-based spatial statistics (TBSS). Additionally, voxel- and region of interest-based analyses were also conducted. At <48 h, the concussed group showed significantly higher axial kurtosis than the control group. These differences increased in extent and magnitude at 8 days, then receded at 15 days, and returned to the normal levels by 45 days. Kurtosis fractional anisotropy (FA) exhibited a delayed response, with a consistent increase by days 15 and 45. The results indicate that changes detected in the acute period appear to be prolonged compared with clinical recovery, but additional brain changes not observable acutely appear to progress. Although further studies are needed to understand the pathological features of DKI changes after SRC, these findings highlight a potential disparity between clinical symptoms and pathophysiological recovery after SRC.

Oswestry Disability Index scores correlate with MRI measurements in degenerating intervertebral discs and endplates.

BACKGROUND: Low back pain (LBP) is a widespread problem and the leading cause of disability worldwide. While the cause of LBP is multifactorial, several studies suggested that inflammatory mediators in damaged subchondral plates of degenerating discs may lead to chemical sensitization and mechanical stimulation, eventually causing pain. The goal of this study was to explore associations between such changes and LBP-related disability using dynamic contrast-enhanced MRI. METHODS: Thirty-two patients diagnosed with nonspecific LBP and 24 healthy control subjects were studied with dynamic contrast-enhanced (DCEMRI) MRI and T1r (spin-lattice relaxation in the rotating frame) acquisitions. DCEMRI enhancement in disc endplate regions and average T1ρ measurements in the nucleus pulposus were extracted. The LBP patients were grouped based on their Oswestry Disability Index (ODI) scores and associations between MRI measurements and ODI scores were analyzed. RESULTS: Significant associations were found between ODI scores and DCEMRI enhancement in the cartilaginous endplate regions of the most degenerated discs. ODI scores also correlated with T1ρ measurements in the nucleus pulposus of degenerating discs. CONCLUSIONS: DCEMRI enhancement in the cartilaginous endplate regions and lower T1ρ measurements in the nucleus pulposus (NP) were associated with greater disability that is related to low back pain as reported on the ODI. This complements earlier reports suggesting a link between LBP and endplate degeneration. Further studies are needed to validate these findings. SIGNIFICANCE: Our findings indicated that dynamic contrast-enhanced MRI signal enhancement in the cartilaginous endplate regions were associated with greater disability related to low back pain. This signal enhancement might be an indication of inflammatory changes in disc endplate regions. Therefore, advanced quantitative imaging techniques like the ones presented in this study might be needed to complement conventional radiological evaluations to identify the subset of patients who could potentially benefit from novel therapies directed towards treating the disc endplate regions.

A high-resolution fMRI investigation of BNST and centromedial amygdala activity as a function of affective stimulus predictability, anticipation, and duration.

Relative to the centromedial amygdala (CM), the bed nucleus of the stria terminalis (BNST) may exhibit more sustained activation toward threat, sensitivity to unpredictability and activation during anxious anticipation. These factors are often intertwined. For example, greater BNST (vs CM) activation during a block of aversive stimuli may reflect either more sustained activation to the stimuli or greater activation due to the anticipation of upcoming stimuli. To further investigate these questions, we had participants (19 females, 9 males) complete a task adapted from a study conducted by Somerville, Whalen and Kelly in 2013, during high-resolution 7-Tesla fMRI BOLD acquisition. We found a larger response to negative vs neutral blocks (sustained threat) than to images (transient) in the BNST, but not the CM. However, in an additional analysis, we also found BNST, but not CM, activation to the onset of the anticipation period on negative vs neutral trials, possibly contributing to BNST activation across negative blocks. Predictability did not affect CM or BNST activation. These results suggest a BNST role in anxious anticipation and highlight the need for further research clarifying the temporal response characteristics of these regions.

Analysis of errors in diffusion kurtosis imaging caused by slice crosstalk in simultaneous multi-slice imaging.

Simultaneous multi-slice (SMS) imaging techniques accelerate diffusion MRI data acquisition. However, slice separation is imperfect and results in residual signal leakage between the simultaneously excited slices. The resulting consistent bias may adversely affect diffusion model parameter estimation. Although this bias is usually small and might not affect the simplified diffusion tensor model significantly, higher order diffusion models such as kurtosis are likely to be more susceptible to such effects. In this work, two SMS reconstruction techniques and an alternative acquisition approach were tested to quantify the effects of slice crosstalk on diffusion kurtosis parameters. In reconstruction, two popular slice separation algorithms, slice GRAPPA and split-slice GRAPPA, are evaluated to determine the effect of slice leakage on diffusion kurtosis metrics. For the alternative acquisition, the slice pairings were varied across diffusion weighted images such that the signal leakage does not come from the same overlapped slice for all diffusion encodings. Simulation results demonstrated the potential benefits of randomizing the slice pairings. However, various experimental factors confounded the advantages of slice pair randomization. In volunteer experiments, region-of-interest analyses found high metric errors with each of the SMS acquisitions and reconstructions in the brain white matter.

Optimization of q-space sampling for mean apparent propagator MRI metrics using a genetic algorithm.

Mean Apparent Propagator (MAP) MRI is a recently introduced technique to estimate the diffusion probability density function (PDF) robustly. Using the estimated PDF, MAP MRI then calculates zero-displacement and non-Gaussianity metrics, which might better characterize tissue microstructure compared to diffusion tensor imaging or diffusion kurtosis imaging. However, intensive q-space sampling required for MAP MRI limits its widespread adoption. A reduced q-space sampling scheme that maintains the accuracy of the derived metrics would make it more practical. A heuristic approach for acquiring MAP MRI with fewer q-space samples has been introduced earlier with scan duration of less than 10 minutes. However, the sampling scheme was not optimized systematically to preserve the accuracy of the model metrics. In this work, a genetic algorithm is implemented to determine optimal q-space subsampling schemes for MAP MRI that will keep total scan time under 10 min. Results show that the metrics derived from the optimized schemes more closely match those computed from the full set, especially in dense fiber tracts such as the corpus callosum.

Chronic differences in white matter integrity following sport-related concussion as measured by diffusion MRI: 6-Month follow-up.

Recent studies demonstrated evidence of physiological changes in the brain following sport-related concussion (SRC) that persisted beyond the point at which athletes achieved full symptom recovery. Diffusion MRI techniques have been used to study brain white matter (WM) changes following SRC; however, longitudinal studies that follow injured athletes from the acute to chronic stages of injury are sparse. The current study explores potential persisting effects of the injury, which serves as a follow-up to our previous work that reported WM changes in the acute and subacute phase of SRC recovery. Concussed high school and collegiate football players (n = 17) and well-matched teammate controls (n = 20) were followed up at 6 months postinjury with diffusion tensor (DTI) and diffusion kurtosis imaging (DKI) as well as measures of self-reported symptoms, cognitive functioning, and balance. Results of tract-based spatial statistics (TBSS) analyses revealed continued widespread decreased mean and axial diffusivity compared to control subjects in 6-month follow-up scans. On the other hand, kurtosis metrics, which were significantly higher in concussed athletes in the acute phase, had normalized. WM tract regions-of-interest (ROIs) were created from significant clusters in the TBSS analysis, and linear mixed effects (LME) analyses were used to look at longitudinal changes in these ROIs over time. LME analyses revealed few time × group interactions indicating findings were relatively stable over time. In addition, acute concussion symptoms predicted diffusivity measures at 6 months postinjury. Findings indicate that DTI and DKI may be useful tools in assessing concussion severity, recovery, and possible long-term effects of concussion.

Filter-probe diffusion imaging improves spinal cord injury outcome prediction.

OBJECTIVE: Diffusion-weighted imaging (DWI) is a powerful tool for investigating spinal cord injury (SCI), but has limited specificity for axonal damage, which is the most predictive feature of long-term functional outcome. In this study, a technique designed to detect acute axonal injury, filter-probe double diffusion encoding (FP-DDE), is compared with standard DWI for predicting long-term functional and cellular outcomes. METHODS: This study extends FP-DDE to predict long-term functional and histological outcomes in a rat SCI model of varying severities (n = 58). Using a 9.4T magnetic resonance imaging (MRI) system, a whole-cord FP-DDE spectroscopic voxel was acquired in 3 minutes at the lesion site and compared to DWI at 48 hours postinjury. Relationships with chronic (30-day) locomotor and histological outcomes were evaluated with linear regression. RESULTS: The FP-DDE measure of parallel diffusivity (ADC|| ) was significantly related to chronic hind limb locomotor functional outcome (R2 = 0.63, p < 0.0001), and combining this measurement with acute functional scores demonstrated prognostic benefit versus functional testing alone (p = 0.0007). Acute ADC|| measurements were also more closely related to the number of injured axons measured 30 days after the injury than standard DWI. Furthermore, acute FP-DDE images showed a clear and easily interpretable pattern of injury that closely corresponded with chronic MRI and histology observations. INTERPRETATION: Collectively, these results demonstrate FP-DDE benefits from greater specificity for acute axonal damage in predicting functional and histological outcomes with rapid acquisition and fully automated analysis, improving over standard DWI. FP-DDE is a promising technique compatible with clinical settings, with potential research and clinical applications for evaluation of spinal cord pathology. Ann Neurol 2018;83:37-50.

Assessing diffusion kurtosis tensor estimation methods using a digital brain phantom derived from human connectome project data.

PURPOSE: Diffusion kurtosis imaging (DKI) has gained popularity in recent years as an advanced diffusion-weighted MRI technique. This work aims to quantitatively compare the performance and accuracy of four DKI processing algorithms. For this purpose, a digital DKI brain phantom is developed. METHODS: Data from the Human Connectome Project database were used to generate a DKI digital phantom. In a Monte Carlo Rician noise simulation, four DKI processing algorithms were compared based on their mean squared error, squared bias, and variance. RESULTS: Algorithm performance was region-dependent and differed for each diffusion metric and noise level. Crossover between variance and squared bias error occurred between signal-to-noise ratios of 30 and 40. CONCLUSION: Through the framework presented here, DKI algorithms can be quantitatively compared via a ground truth data set. Error maps are critical as algorithm performance varies spatially. Bias-plus-variance decomposition provides a more complete picture than MSE alone. In combination with refinements in acquisition in future studies, the accuracy and efficiency of DKI will continue to improve promoting clinical adoption.

Stability of MRI metrics in the advanced research core of the NCAA-DoD concussion assessment, research and education (CARE) consortium.

The NCAA-DoD Concussion Assessment, Research, and Education (CARE) consortium is performing a large-scale, comprehensive study of sport related concussions in college student-athletes and military service academy cadets. The CARE "Advanced Research Core" (ARC), is focused on executing a cutting-edge investigative protocol on a subset of the overall CARE athlete population. Here, we present the details of the CARE ARC MRI acquisition and processing protocol along with preliminary analyzes of within-subject, between-site, and between-subject stability across a variety of MRI biomarkers. Two experimental datasets were utilized for this analysis. First, two "human phantom" subjects were imaged multiple times at each of the four CARE ARC imaging sites, which utilize equipment from two imaging vendors. Additionally, a control cohort of healthy athletes participating in non-contact sports were enrolled in the study at each CARE ARC site and imaged at four time points. Multiple morphological image contrasts were acquired in each MRI exam; along with quantitative diffusion, functional, perfusion, and relaxometry imaging metrics. As expected, the imaging markers were found to have varying levels of stability throughout the brain. Importantly, between-subject variance was generally found to be greater than within-subject and between-site variance. These results lend support to the expectation that cross-site and cross-vendor advanced quantitative MRI metrics can be utilized to improve analytic power in assessing sensitive neurological variations; such as those effects hypothesized to occur in sports-related-concussion. This stability analysis provides a crucial foundation for further work utilizing this expansive dataset, which will ultimately be freely available through the Federal Interagency Traumatic Brain Injury Research Informatics System.

Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala-BNST connectivity during periods of threat vs safety.

Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants' self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala-BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism.