Magnetic resonance spectroscopy investigation in the right human hippocampus following spinal cord injury.

OBJECTIVE Preclinical studies have shown that cognitive impairments following spinal cord injury (SCI), such as impaired spatial memory, are linked to inflammation, neurodegeneration, and reduced neurogenesis in the right hippocampus. This cross-sectional study aims to characterize metabolic and macrostructural changes in the right hippocampus and their association to cognitive function in traumatic SCI patients. METHODS Within this cross-sectional study, cognitive function was assessed in 28 chronic traumatic SCI patients and 18 age-, sex-, and education-matched healthy controls by a visuospatial and verbal memory test. A magnetic resonance spectroscopy (MRS) and structural MRI protocol was performed in the right hippocampus of both groups to quantify metabolic concentrations and hippocampal volume, respectively. Group comparisons investigated changes between SCI patients and healthy controls and correlation analyses investigated their relationship to memory performance. RESULTS Memory performance was similar in SCI patients and healthy controls. The quality of the recorded MR spectra was excellent in comparison to the best-practice reports for the hippocampus. Metabolite concentrations and volume of the hippocampus measured based on MRS and MRI were not different between two groups. Memory performance in SCI patients and healthy controls was not correlated with metabolic or structural measures. CONCLUSION This study suggests that the hippocampus may not be pathologically affected at a functional, metabolic, and macrostructural level in chronic SCI. This points toward the absence of significant and clinically relevant trauma-induced neurodegeneration in the hippocampus

Magnetic resonance spectroscopy investigation in the right human hippocampus following spinal cord injury

OBJECTIVE Preclinical studies have shown that cognitive impairments following spinal cord injury (SCI), such as impaired spatial memory, are linked to inflammation, neurodegeneration, and reduced neurogenesis in the right hippocampus. This cross-sectional study aims to characterize metabolic and macrostructural changes in the right hippocampus and their association to cognitive function in traumatic SCI patients. METHODS Within this cross-sectional study, cognitive function was assessed in 28 chronic traumatic SCI patients and 18 age-, sex-, and education-matched healthy controls by a visuospatial and verbal memory test. A magnetic resonance spectroscopy (MRS) and structural MRI protocol was performed in the right hippocampus of both groups to quantify metabolic concentrations and hippocampal volume, respectively. Group comparisons investigated changes between SCI patients and healthy controls and correlation analyses investigated their relationship to memory performance. RESULTS Memory performance was similar in SCI patients and healthy controls. The quality of the recorded MR spectra was excellent in comparison to the best-practice reports for the hippocampus. Metabolite concentrations and volume of the hippocampus measured based on MRS and MRI were not different between two groups. Memory performance in SCI patients and healthy controls was not correlated with metabolic or structural measures. CONCLUSION This study suggests that the hippocampus may not be pathologically affected at a functional, metabolic, and macrostructural level in chronic SCI. This points toward the absence of significant and clinically relevant trauma-induced neurodegeneration in the hippocampus

Beyond Frameworks: Structuring Reticular Materials across Nano‐, Meso‐, and Bulk Regimes

Reticular materials are of high interest for diverse applications, ranging from catalysis and separation to gas storage and drug delivery. These open, extended frameworks can be tailored to the intended application through crystal‐structure design. Implementing these materials in application settings, however, requires structuring beyond their lattices, to interface the functionality at the molecular level effectively with the macroscopic world. To overcome this barrier, efforts in expressing structural control across molecular, nano‐, meso‐, and bulk regimes is the essential next step. In this Review, we give an overview of recent advances in using self‐assembly as well as externally controlled tools to manufacture reticular materials over all the length scales. We predict that major research advances in deploying these two approaches will facilitate the use of reticular materials in addressing major needs of society

Improved inter-subject alignment of the lumbosacral cord for group-level in vivo gray and white matter assessments: A scan-rescan MRI study at 3T

INTRODUCTION: Magnetic resonance imaging (MRI) enables the investigation of pathological changes in gray and white matter at the lumbosacral enlargement (LSE) and conus medullaris (CM). However, conducting group-level analyses of MRI metrics in the lumbosacral spinal cord is challenging due to variability in CM length, lack of established image-based landmarks, and unknown scan-rescan reliability. This study aimed to improve inter-subject alignment of the lumbosacral cord to facilitate group-level analyses of MRI metrics. Additionally, we evaluated the scan-rescan reliability of MRI-based cross-sectional area (CSA) measurements and diffusion tensor imaging (DTI) metrics. METHODS: Fifteen participants (10 healthy volunteers and 5 patients with spinal cord injury) underwent axial T2*-weighted and diffusion MRI at 3T. We assessed the reliability of spinal cord and gray matter-based landmarks for inter-subject alignment of the lumbosacral cord, the inter-subject variability of MRI metrics before and after adjusting for the CM length, the intra- and inter-rater reliability of CSA measurements, and the scan-rescan reliability of CSA measurements and DTI metrics. RESULTS: The slice with the largest gray matter CSA as an LSE landmark exhibited the highest reliability, both within and across raters. Adjusting for the CM length greatly reduced the inter-subject variability of MRI metrics. The intra-rater, inter-rater, and scan-rescan reliability of MRI metrics were the highest at and around the LSE (scan-rescan coefficient of variation <3% for CSA measurements and <7% for DTI metrics within the white matter) and decreased considerably caudal to it. CONCLUSIONS: To facilitate group-level analyses, we recommend using the slice with the largest gray matter CSA as a reliable LSE landmark, along with an adjustment for the CM length. We also stress the significance of the anatomical location within the lumbosacral cord in relation to the reliability of MRI metrics. The scan-rescan reliability values serve as valuable guides for power and sample size calculations in future longitudinal studies

Progressive neurodegeneration following spinal cord injury: Implications for clinical trials.

OBJECTIVE: To quantify atrophy, demyelination, and iron accumulation over 2 years following acute spinal cord injury and to identify MRI predictors of clinical outcomes and determine their suitability as surrogate markers of therapeutic intervention. METHODS: We assessed 156 quantitative MRI datasets from 15 patients with spinal cord injury and 18 controls at baseline and 2, 6, 12, and 24 months after injury. Clinical recovery (including neuropathic pain) was assessed at each time point. Between-group differences in linear and nonlinear trajectories of volume, myelin, and iron change were estimated. Structural changes by 6 months were used to predict clinical outcomes at 2 years. RESULTS: The majority of patients showed clinical improvement with recovery stabilizing at 2 years. Cord atrophy decelerated, while cortical white and gray matter atrophy progressed over 2 years. Myelin content in the spinal cord and cortex decreased progressively over time, while cerebellar loss decreases decelerated. As atrophy progressed in the thalamus, sustained iron accumulation was evident. Smaller cord and cranial corticospinal tract atrophy, and myelin changes within the sensorimotor cortices, by 6 months predicted recovery in lower extremity motor score at 2 years. Whereas greater cord atrophy and microstructural changes in the cerebellum, anterior cingulate cortex, and secondary sensory cortex by 6 months predicted worse sensory impairment and greater neuropathic pain intensity at 2 years. CONCLUSION: These results draw attention to trauma-induced neuroplastic processes and highlight the intimate relationships among neurodegenerative processes in the cord and brain. These measurable changes are sufficiently large, systematic, and predictive to render them viable outcome measures for clinical trials

Tracking trauma-induced structural and functional changes above the level of spinal cord injury

PURPOSE OF REVIEW: This review will highlight the latest findings from neuroimaging studies that track structural and functional changes within the central nervous system at both the brain and spinal cord levels following acute human spinal cord injury (SCI). The putative, underlying biological mechanisms of structural change (e.g. degradation of neural tissue) rostral to the lesion site will be discussed in relation to animal models of SCI and their potential value in clinical studies of human SCI. RECENT FINDINGS: Recent prospective studies in human acute SCI have begun to reveal the time-course, spatial distribution and extent of structural changes following an acute SCI and their relation to functional outcome. Adaptive changes in sensory and motor pathways above the level of the lesion have prognostic value and complement clinical readouts. SUMMARY: The introduction of sensitive neuroimaging biomarkers will be an essential step forward in the implementation of interventional trials in which proof-of-concept is currently limited to clinical readouts, but more responsive measures are required to improve the sensitivity of clinical trials

Optimized multi-echo gradient-echo magnetic resonance imaging for gray and white matter segmentation in the lumbosacral cord at 3 T

Atrophy in the spinal cord (SC), gray (GM) and white matter (WM) is typically measured in-vivo by image segmentation on multi-echo gradient-echo magnetic resonance images. The aim of this study was to establish an acquisition and analysis protocol for optimal SC and GM segmentation in the lumbosacral cord at 3 T. Ten healthy volunteers underwent imaging of the lumbosacral cord using a 3D spoiled multi-echo gradient-echo sequence (Siemens FLASH, with 5 echoes and 8 repetitions) on a Siemens Prisma 3 T scanner. Optimal numbers of successive echoes and signal averages were investigated comparing signal-to-noise (SNR) and contrast-to-noise ratio (CNR) values as well as qualitative ratings for segmentability by experts. The combination of 5 successive echoes yielded the highest CNR between WM and cerebrospinal fluid and the highest rating for SC segmentability. The combination of 3 and 4 successive echoes yielded the highest CNR between GM and WM and the highest rating for GM segmentability in the lumbosacral enlargement and conus medullaris, respectively. For segmenting the SC and GM in the same image, we suggest combining 3 successive echoes. For SC or GM segmentation only, we recommend combining 5 or 3 successive echoes, respectively. Six signal averages yielded good contrast for reliable SC and GM segmentation in all subjects. Clinical applications could benefit from these recommendations as they allow for accurate SC and GM segmentation in the lumbosacral cord

Reliability of spinal cord measures based on synthetic T1_{1}-weighted MRI derived from multiparametric mapping (MPM)

Short MRI acquisition time, high signal-to-noise ratio, and high reliability are crucial for image quality when scanning healthy volunteers and patients. Cross-sectional cervical cord area (CSA) has been suggested as a marker of neurodegeneration and potential outcome measure in clinical trials and is conventionally measured on T$_{1}$-weigthed 3D Magnetization Prepared Rapid Acquisition Gradient-Echo (MPRAGE) images. This study aims to reduce the acquisition time for the comprehensive assessment of the spinal cord, which is typically based on MPRAGE for morphometry and multi-parameter mapping (MPM) for microstructure. The MPRAGE is replaced by a synthetic T$_{1}$-w MRI (synT$_{1}$-w) estimated from the MPM, in order to measure CSA. SynT$_{1}$-w images were reconstructed using the MPRAGE signal equation based on quantitative maps of proton density (PD), longitudinal (R$_{1}$) and effective transverse (R$_{2}$*) relaxation rates. The reliability of CSA measurements from synT$_{1}$-w images was determined within a multi-center test-retest study format and validated against acquired MPRAGE scans by assessing the agreement between both methods. The response to pathological changes was tested by longitudinally measuring spinal cord atrophy following spinal cord injury (SCI) for synT$_{1}$-w and MPRAGE using linear mixed effect models. CSA measurements based on the synT$_{1}$-w MRI showed high intra-site (Coefficient of variation [CoV]: 1.43% to 2.71%) and inter-site repeatability (CoV: 2.90% to 5.76%), and only a minor deviation of -1.65 mm$^{2}$ compared to MPRAGE. Crucially, by assessing atrophy rates and by comparing SCI patients with healthy controls longitudinally, differences between synT$_{1}$-w and MPRAGE were negligible. These results demonstrate that reliable estimates of CSA can be obtained from synT$_{1}$-w images, thereby reducing scan time significantly

Cross-checking to reduce adverse events resulting from medical errors in the emergency department: study protocol of the CHARMED cluster randomized study

International audienceBackgroundMedical errors and preventable adverse events are a major cause of concern, especially in the emergency department (ED) where its prevalence has been reported to be roughly of 5–10 % of visits. Due to a short length of stay, emergency patients are often managed by a sole physician – in contrast with other specialties where they can benefit from multiples handover, ward rounds and staff meetings. As some studies report that the rate and severity of errors may decrease when there is more than one physician involved in the management in different settings, we sought to assess the impact of regular systematic cross-checkings between physicians in the ED.DesignThe CHARMED (Cross-checking to reduce adverse events resulting from medical errors in the emergency department) study is a multicenter cluster randomized study that aim to evaluate the reduction of the rate of severe medical errors with implementation of systematic cross checkings between emergency physician, compared to a control period with usual care. This study will evaluate the effect of this intervention on the rate of severe medical errors (i.e. preventable adverse events or near miss) using a previously described two-level chart abstraction. We made the hypothesis that implementing frequent and systematic cross checking will reduce the rate of severe medical errors from 10 to 6 % - 1584 patients will be included, 140 for each period in each center.DiscussionThe CHARMED study will be the largest study that analyse unselected ED charts for medical errors. This could provide evidence that frequent systematic cross-checking will reduce the incidence of severe medical errors

Kaehler forms and cosmological solutions in type II supergravities

We consider cosmological solutions to type II supergravity theories where the spacetime is split into a FRW universe and a K\"ahler space, which may be taken to be Calabi-Yau. The various 2-forms present in the theories are taken to be proportional to the K\"ahler form associated to the K\"ahler space.Comment: 6 pages, LaTeX2