Brain functioning relies on various segregated/specialized neural regions functioning as an integrated-interconnected network (i.e., metastability). Various psychiatric and neurologic disorders are ...associated with aberrant functioning of these brain networks. In this study, we present a novel framework integrating the strength and temporal variability of metastability in brain networks. We demonstrate that this approach provides novel mechanistic insights which enables better imaging-based predictions. Using whole-brain resting-state fMRI and a graph-theoretic framework, we integrated strength and temporal-variability of complex-network properties derived from effective connectivity networks, obtained from 87 U.S. Army soldiers consisting of healthy combat controls (
= 28), posttraumatic stress disorder (PTSD;
= 17), and PTSD with comorbid mild-traumatic brain injury (mTBI;
= 42). We identified prefrontal dysregulation of key subcortical and visual regions in PTSD/mTBI, with all network properties exhibiting lower variability over time, indicative of poorer flexibility. Larger impairment in the prefrontal-subcortical pathway but not prefrontal-visual pathway differentiated comorbid PTSD/mTBI from the PTSD group. Network properties of the prefrontal-subcortical pathway also had significant association (
= 0.56) with symptom severity and neurocognitive performance; and were also found to possess high predictive ability (81.4% accuracy in classifying the disorders, explaining 66-72% variance in symptoms), identified through machine learning. Our framework explained 13% more variance in behaviors compared to the conventional framework. These novel insights and better predictions were made possible by our novel framework using static and time-varying network properties in our three-group scenario, advancing the mechanistic understanding of PTSD and comorbid mTBI. Our contribution has wide-ranging applications for network-level characterization of healthy brains as well as mental disorders.
Left atrial (LA) strain is impaired in left ventricular (LV) diastolic dysfunction, associated with increased LV end diastolic pressure (LVEDP). In patients with preserved LV ejection fraction ...(LVEF), coronary artery disease (CAD) is known to impair LV diastolic function. The relationship of LVEDP with CAD and impact on LA strain is not well studied.
Patients with LVEF >50% (n = 37, age 61 ± 7 years) underwent coronary angiography, high-fidelity LV pressure measurements and cardiac magnetic resonance imaging. LA volumes, LA emptying fraction (LAEF), LA reservoir strain (LARS) and LA long-axis shortening (LALAS) were measured. By coronary angiography, patients were assigned into 3 groups: severe-CAD (n = 19, with obstruction of major coronary arteries >70% and/or history of coronary revascularization), mild-to-moderate-CAD (n = 10, obstruction of major coronary arteries 30–60%), and no-CAD (n = 8, obstruction of major coronary arteries and branches <30%). Overall, LVEF was 65 ± 8% and LVEDP was 14.4 ± 5.6 mmHg. Clinical characteristics, LVEDP and LV function measurements were similar in 3 groups. Severe-CAD group had lower LAEF, LALAS and LARS than those in no-CAD group (P < 0.05 all). In regression analysis, LARS and LALAS were associated with CAD severity and treatment with Nitrates, whereas LAEF and LAEFactive were associated with CAD severity, treatment with Nitrates and LA minimum volume (P < 0.05 all). LAEFpassive was associated with LVED volume (P < 0.05).
LA functional impairment may be affected by coexistent CAD severity, medications, in particular, Nitrates, and loading conditions, which should be considered when assessing LA function and LA-LV interaction. Our findings inspire exploration in a larger cohort.
•LA strain and function are impaired in CAD regardless of LVEDP.•LA function may be affected by coexistent CAD severity, medications and loading conditions.•LA strain alone may be insufficient to accurately predict LVEDP in patients with CAD.
Mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are characterized by blood-brain barrier (BBB) breakdown leading to abnormal BBB permeability ahead of brain atrophy or dementia. ...Previous findings in AD mouse models have reported the beneficial effect of extra-virgin olive oil (EVOO) against AD, which improved BBB and memory functions and reduced brain amyloid-β (Aβ) and related pathology. This work aimed to translate these preclinical findings to humans in individuals with MCI. We examined the effect of daily consumption of refined olive oil (ROO) and EVOO for 6 months in MCI subjects on BBB permeability (assessed by contrast-enhanced MRI), and brain function (assessed using functional-MRI) as the primary outcomes. Cognitive function and AD blood biomarkers were also assessed as the secondary outcomes. Twenty-six participants with MCI were randomized with 25 participants completed the study. EVOO significantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functional connectivity. While ROO consumption did not alter BBB permeability or brain connectivity, it improved CDR scores and increased functional brain activation to a memory task in cortical regions involved in perception and cognition. Moreover, EVOO and ROO significantly reduced blood Aβ
/Aβ
and p-tau/t-tau ratios, suggesting that both altered the processing and clearance of Aβ. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect. This proof-of-concept study justifies further clinical trials to assess olive oil's protective effects against AD and its potential role in preventing MCI conversion to AD and related dementias.
Creatine Kinase (CK) reaction plays an important role in energy metabolism and estimate of its reaction rate constant in heart provides important insight into cardiac energetics. Fast saturation ...transfer method (Formula: see text nominal) to measure CK reaction rate constant (kf) was previously demonstrated in open chest swine hearts. The goal of this work is to further develop this method for measuring the kf in human myocardium at 7T. Formula: see text approach is combined with 1D-ISIS/2D-CSI for in vivo spatial localization and myocardial CK forward rate constant was then measured in 7 volunteers at 7T.
Formula: see text method uses two partially relaxed saturation transfer (ST) spectra and correction factor to determine CK rate constant. Correction factor is determined by numerical simulation of Bloch McConnell equations using known spin and experimental parameters. Optimal parameters and error estimate in calculation of CK reaction rate constant were determined by simulations. The technique was validated in calf muscles by direct comparison with saturation transfer measurements. Formula: see text pulse sequence was incorporated with 1D-image selected in vivo spectroscopy, combined with 2D-chemical shift spectroscopic imaging (1D-ISIS/2D-CSI) for studies in heart. The myocardial CK reaction rate constant was then measured in 7 volunteers.
Skeletal muscle kf determined by conventional approach and Formula: see text approach were the same 0.31 ± 0.02 s-1 and 0.30 ± 0.04 s-1 demonstrating the validity of the technique. Results are reported as mean ± SD. Myocardial CK reaction rate constant was 0.29 ± 0.05 s-1, consistent with previously reported studies.
Formula: see text method enables acquisition of 31P saturation transfer MRS under partially relaxed conditions and enables 2D-CSI of kf in myocardium. This work enables applications for in vivo CSI imaging of energetics in heart and other organs in clinically relevant acquisition time.
Functional brain connectivity based on resting-state functional magnetic resonance imaging (fMRI) has been shown to be correlated with human personality and behavior. In this study, we sought to know ...whether capabilities and traits in dogs can be predicted from their resting-state connectivity, as in humans. We trained awake dogs to keep their head still inside a 3T MRI scanner while resting-state fMRI data was acquired. Canine behavior was characterized by an integrated behavioral score capturing their hunting, retrieving, and environmental soundness. Functional scans and behavioral measures were acquired at three different time points across detector dog training. The first time point (TP1) was prior to the dogs entering formal working detector dog training. The second time point (TP2) was soon after formal detector dog training. The third time point (TP3) was three months' post detector dog training while the dogs were engaged in a program of maintenance training for detection work. We hypothesized that the correlation between resting-state FC in the dog brain and behavior measures would significantly change during their detection training process (from TP1 to TP2) and would maintain for the subsequent several months of detection work (from TP2 to TP3). To further study the resting-state FC features that can predict the success of training, dogs at TP1 were divided into a successful group and a non-successful group. We observed a core brain network which showed relatively stable (with respect to time) patterns of interaction that were significantly stronger in successful detector dogs compared to failures and whose connectivity strength at the first time point predicted whether a given dog was eventually successful in becoming a detector dog. A second ontologically based flexible peripheral network was observed whose changes in connectivity strength with detection training tracked corresponding changes in behavior over the training program. Comparing dog and human brains, the functional connectivity between the brain stem and the frontal cortex in dogs corresponded to that between the locus coeruleus and left middle frontal gyrus in humans, suggestive of a shared mechanism for learning and retrieval of odors. Overall, the findings point toward the influence of phylogeny and ontogeny in dogs producing two dissociable functional neural networks.
Abstract
Recent magnetic resonance spectroscopy (MRS) studies suggest that abnormalities of the glutamatergic system in schizophrenia may be dependent on illness stage, medication status, and ...symptomatology. Glutamatergic metabolites appear to be elevated in the prodromal and early stages of schizophrenia but unchanged or reduced below normal in chronic, medicated patients. However, few of these studies have measured metabolites with high-field 7T MR scanners, which offer higher signal-to-noise ratio and better spectral resolution than 3T scanners and facilitate separation of glutamate and glutamine into distinct signals. In this study, we examined glutamate and other metabolites in the dorsal anterior cingulate cortex (ACC) of first-episode schizophrenia patients. Glutamate and N-acetylaspartate (NAA) were significantly lower in schizophrenia patients vs controls. No differences were observed in levels of glutamine, GABA, or other metabolites. In schizophrenia patients but not controls, GABA was negatively correlated with the total score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as well as the immediate memory and language subscales. Our findings suggest that glutamate and NAA reductions in the ACC may be present early in the illness, but additional large-scale studies are needed to confirm these results as well as longitudinal studies to determine the effect of illness progression and treatment. The correlation between GABA and cognitive function suggests that MRS may be an important technique for investigating the neurobiology underlying cognitive deficits in schizophrenia.
Background
Tissue Doppler index E/è is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with ...preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied.
Methods and Results
From the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/è and invasive LVFP in preserved EF (≥50%). In random‐effects models, E/è had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography–recommended E/è cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9–48%), 37% (13–61%), and 24% (6–46%), and summary specificity was 92% (82–100%), 91% (80–99%), and 98% (92–100%). Positive likelihood ratio (LR+) was <5 for lateral and mean E/è. LR+ was slightly >10 for septal E/è obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/è (lateral, mean, and septal, respectively) was 64% (38–86%), 36% (3–74%), and 50% (14–81%), while summary specificity was 73% (54–89%), 83% (49–100%), and 89% (66–100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/è could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability.
Conclusions
There is insufficient evidence to support that E/è can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/è to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well‐designed prospective clinical trial.
MRI is a valuable diagnostic tool to investigate spinal cord (SC) pathology. SC MRI can benefit from the increased signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at ultra-high fields ...such as 7 T. However, SC MRI acquisitions with routine Cartesian readouts are prone to image artifacts caused by physiological motion. MRI acquisition techniques with non-Cartesian readouts such as rosette can help reduce motion artifacts. The purpose of this study was to demonstrate the feasibility of high-resolution SC imaging using rosette trajectory with magnetization transfer preparation (MT-prep) and compressed sensing (CS) at 7 T. Five healthy volunteers participated in the study. Images acquired with rosette readouts demonstrated reduced motion artifacts compared to the standard Cartesian readouts. The combination of multi-echo rosette-readout images improved the CNR by approximately 50% between the gray matter (GM) and white matter (WM) compared to single-echo images. MT-prep images showed excellent contrast between the GM and WM with magnetization transfer ratio (MTR) and cerebrospinal fluid normalized MT signal (MTCSF) = 0.12 ± 0.017 and 0.74 ± 0.013, respectively, for the GM; and 0.18 ± 0.011 and 0.58 ± 0.009, respectively, for the WM. Under-sampled acquisition using rosette readout with CS reconstruction demonstrated up to 6 times faster scans with comparable image quality as the fully-sampled acquisition.
Magnetic resonance spectroscopic imaging (MRSI) provides information about the spatial distribution of metabolites in the brain. These metabolite maps can be valuable in diagnosing central nervous ...system pathology. However, MRSI generally suffers from a long acquisition time, poor spatial resolution, and a low metabolite signal‐to‐noise ratio (SNR). Ultrahigh field strengths (≥ 7 T) can benefit MRSI with an improved SNR and allow high‐resolution metabolic mapping. Non‐Cartesian spatial‐spectral encoding techniques, such as rosette spectroscopic imaging, can efficiently sample spatial and temporal domains, which significantly reduces the imaging time and enables high‐resolution metabolic mapping in a clinically relevant scan time. In the current study, high‐resolution (in‐plane resolution of 2 × 2 mm2) mapping of proton (1H) metabolites in the human brain at 7 T, is demonstrated. Five healthy subjects participated in the study. Using a time‐efficient rosette trajectory and short TR/TE free induction decay MRSI, high‐resolution maps of 1H metabolites were obtained in a clinically relevant imaging time (6 min). Suppression of the water signal was achieved with an optimized water suppression enhanced through T1 effects approach and lipid removal was performed using L2‐regularization in the postprocessing. Spatial distributions of N‐acetyl‐aspartate, total choline, creatine, N‐acetyl‐aspartyl glutamate, myo‐inositol, and glutamate were generated with Cramer–Rao lower bounds of less than 20%.
A nonlipid‐suppressed 1H FID magnetic resonance spectroscopic imaging (MRSI) technique using a rosette trajectory is demonstrated for mapping major 1H metabolites in the human brain at 7 T. This technique can generate major 1H metabolic maps with an in‐plane resolution of 2 mm in an acquisition time of less than 6 min for a single slice. This technique is fast and can be very useful for clinical applications.
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