Prediction of the Impact of Craniospinal Compliance on the Relative Timing of Arterial and Cerebrospinal Fluid Pulsations and Perivascular Fluid Flow Into the Spinal Cord

ABSTRACT Craniospinal compliance (CC) has been hypothesized to have importance in craniospinal disorders such as hydrocephalus and syringomyelia in which tissue edema occurs. In this study we assess the impact of CC on 1) the relative timing of spinal cord blood flow (SCBF) and cerebrospinal fluid (CSF) pulsations and 2) perivascular flow (PVS) into the spinal cord (SC). A previously developed coupled model of the cardiovascular and CSF system is utilized to obtain the results. The results predict that CC can significantly alter the relative timing of arterial and CSF pulsations in the spine and total perivascular flow to the SC. CC was found to have the greatest impact on relative timing and PVF in the lumbar spine and to a lesser extent in the cervical and thoracic spine. A reduction in CC resulted in increased PVF to the SC that might help to explain tissue edema present in craniospinal disorders with reduced CC

Ventricle Equilibrium Position in Healthy and Normal Pressure Hydrocephalus Brains Using an Analytical Model

The driving force that causes enlargement of the ventricles remains unclear in case of normal pressure hydrocephalus (NPH). Both healthy and NPH brain conditions are characterized by a low transparenchymal pressure drop, typically 1 mm Hg. The present paper proposes an analytical model for normal and NPH brains using Darcy's and Biot's equations and simplifying the brain geometry to a hollow sphere with an internal and external radius. Self-consistent solutions for the large deformation problem that is associated with large ventricle dilation are presented and the notion of equilibrium or stable ventricle position is highlighted for both healthy and NPH conditions. The influence of different biomechanical parameters on the stable ventricle geometry is assessed and it is shown that both CSF seepage through the ependyma and parenchymal permeability play a key role. Although very simple, the present model is able to predict the onset and development of NPH conditions as a deviation from healthy conditions. [DOI: 10.1115/1.4006466

MRI-based Quantification of Optic Nerve Tortuosity and Subarachnoid Space 3D Geometry: Reliability Assessment

In some astronauts, long-duration space flight results in ophthalmic structure changes such as optic nerve (ON) kinking, ON distention, and globe flattening. Assessment of the ON and ON sheath (ONS) may provide insight into the mechanisms responsible for ophthalmic structure changes seen in a subset of astronauts. Automated and manual methods were developed to quantify 3D ON/ONS geometry and ON tortuosity

Cerebrospinal fluid velocity amplitudes within the cerebral aqueduct in healthy children and patients with Chiari I malformation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133626/1/jmri25160_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133626/2/jmri25160.pd

Centuries of intense surface melt on Larsen C Ice Shelf

Following a southward progression of ice-shelf disintegration along the Antarctic Peninsula, Larsen C Ice Shelf is the focus of ongoing investigation regarding its future stability. The ice shelf is known to be experience surface melt, and commonly features surface meltwater ponds. Here, we use a flowline model and a firn density model to date and interpret observations of melt-affected ice layers found within five 90?m boreholes distributed across the ice shelf. We find that units of ice within the boreholes, which have densities exceeding those expected under normal compaction metamorphism, correspond to two climatic warm periods within the last 300 years on the Antarctic Peninsula. The more recent warm period, from the 1960s onwards, has generated distinct sections of dense ice in two boreholes in Cabinet Inlet, close to the Antarctic Peninsula mountains ? a region currently affected by f?hn winds. Previous work has classified these layers as refrozen pond ice, requiring large quantities of mobile liquid water to form. Our flowline model shows that, whilst preconditioning of the ice began in the late 1960s, it was probably not until the early 1990s that twentieth-century ponding began. The earlier warm period occurred during the 18th century and resulted in two additional sections of anomalously dense ice deep within the boreholes. The first, in one of the Cabinet Inlet boreholes, consists of ice characteristic of refrozen ponds and must have formed in an area currently featuring ponding. The second, in a mid-shelf borehole, formed at the same time in an area which now experiences significant annual melt. Further south on the shelf, the boreholes sample ice that is of an equivalent age but which does not exhibit the same degree of melt influence. This west?east and north?south gradient in past melt distribution resembles current spatial patterns of surface melt intensity. Using flowlines to trace the advection and submergence of continental ice identified in boreholes, we demonstrate that, even by the time the ice reaches the calving front, only the upper 40 to 50?% of the shelf is composed of meteoric ice accumulated on the shelf. This vertical composition implies that basal crevasses must be confined within continental and/or basally accreted ice, and therefore will be unaffected by current climate-induced firn compactionauthorsversio

Ice and firn heterogeneity within Larsen C Ice Shelf from borehole optical televiewing

Research was funded by the UK Natural Environmental Research Council grants NE/L006707/1 and NE/L005409/1 and a HEFCW/Aberystwyth University Capital Equipment Grant to B.H. Data will be available via the project website (www.projectmidas.org) and the UK Polar Data Centre (https://www.bas.ac.uk/data/uk-pdc/) from mid-2017.We use borehole optical televiewing (OPTV) to explore the internal structure of Larsen C Ice Shelf (LCIS). We report a suite of five ~90 m long OPTV logs, recording a light-emitting diode-illuminated, geometrically correct image of the borehole wall, from the northern and central sectors of LCIS collected during austral spring 2014 and 2015. We use a thresholding-based technique to estimate the refrozen ice content of the ice column and exploit a recently calibrated density-luminosity relationship to reveal its structure. All sites are dense and strongly influenced by surface melt, with frequent refrozen ice layers and mean densities, between the depths of 1.87 and 90 m, ranging from 862 to 894 kg m−3. We define four distinct units that comprise LCIS and relate these to ice provenance, dynamic history, and past melt events. These units are in situ meteoric ice with infiltration ice (U1), meteoric ice which has undergone enhanced densification (U2), thick refrozen ice (U3), and advected continental ice (U4). We show that the OPTV-derived pattern of firn air content is consistent with previous estimates, but that a significant proportion of firn air is contained within U4, which we interpret to have been deposited inland of the grounding line. The structure of LCIS is strongly influenced by the E-W gradient in föhn-driven melting, with sites close to the Antarctic Peninsula being predominantly composed of refrozen ice. Melting is also substantial toward the ice shelf center with >40% of the overall imaged ice column being composed of refrozen ice.Publisher PDFPeer reviewe

Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients.

BACKGROUND: Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF. Therefore, a method to quantify these dynamics and a characterization of differences across disease states is needed. METHODS: Complete intrathecal 3D CSF geometry and CSF flow velocities at six axial locations in the spinal canal were collected by T2-weighted and phase-contrast MRI, respectively. Scans were completed for eight people with ALS and ten healthy controls. Manual segmentation of the spinal subarachnoid space was performed and coupled with an interpolated model of CSF flow within the spinal canal. Geometric and hydrodynamic parameters were then generated at 1 mm slice intervals along the entire spine. Temporal analysis of the waveform spectral content and feature points was also completed. RESULTS: Comparison of ALS and control groups revealed a reduction in CSF flow magnitude and increased flow propagation velocities in the ALS cohort. Other differences in spectral harmonic content and geometric comparisons may support an overall decrease in intrathecal compliance in the ALS group. Notably, there was a high degree of variability between cases, with one ALS patient displaying nearly zero CSF flow along the entire spinal canal. CONCLUSION: While our sample size limits statistical confidence about the differences observed in this study, it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner. Our study also shows the potential for MRI based measurements of CSF geometry and flow to provide information about the hydrodynamic environment of the spinal subarachnoid space. These dynamics may be studied further to understand the behavior of CSF solute transport in healthy and diseased states

Massive subsurface ice formed by refreezing of ice-shelf melt ponds

Surface melt ponds form intermittently on several Antarctic ice shelves. Although implicated in ice-shelf break up, the consequences of such ponding for ice formation and ice-shelf structure have not been evaluated. Here we report the discovery of a massive subsurface ice layer, at least 16 km across, several kilometres long and tens of metres deep, located in an area of intense melting and intermittent ponding on Larsen C Ice Shelf, Antarctica. We combine borehole optical televiewer logging and radar measurements with remote sensing and firn modelling to investigate the layer, found to be ∼10 C warmer and ∼170 kg m¯³ denser than anticipated in the absence of ponding and hitherto used in models of ice-shelf fracture and flow. Surface ponding and ice layers such as the one we report are likely to form on a wider range of Antarctic ice shelves in response to climatic warming in forthcoming decades

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations