Optimized cervical spinal cord perfusion MRI after traumatic injury in the rat

Despite the potential to guide clinical management of spinal cord injury and disease, noninvasive methods of monitoring perfusion status of the spinal cord clinically remain an unmet need. In this study, we optimized pseudo-continuous arterial spin labeling (pCASL) for the rodent cervical spinal cord and demonstrate its utility in identifying perfusion deficits in an acute contusion injury model. High-resolution perfusion sagittal images with reduced imaging artifacts were obtained with optimized background suppression and imaging readout. Following moderate contusion injury, perfusion was clearly and reliably decreased at the site of injury. Implementation of time-encoded pCASL confirmed injury site perfusion deficits with blood flow measurements corrected for variability in arterial transit times. The noninvasive protocol of pCASL in the spinal cord can be utilized in future applications to examine perfusion changes after therapeutic interventions in the rat and translation to patients may offer critical implications for patient management.Neuro Imaging Researc

Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth.

Structural microtubule associated proteins (MAPs) stabilize microtubules, a property that was thought to be essential for development, maintenance and function of neuronal circuits. However, deletion of the structural MAPs in mice does not lead to major neurodevelopment defects. Here we demonstrate a role for MAP6 in brain wiring that is independent of microtubule binding. We find that MAP6 deletion disrupts brain connectivity and is associated with a lack of post-commissural fornix fibres. MAP6 contributes to fornix development by regulating axonal elongation induced by Semaphorin 3E. We show that MAP6 acts downstream of receptor activation through a mechanism that requires a proline-rich domain distinct from its microtubule-stabilizing domains. We also show that MAP6 directly binds to SH3 domain proteins known to be involved in neurite extension and semaphorin function. We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during the development of cerebral axon tracts

An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors

Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines

Erbb4 deletion from inhibitory interneurons causes psychosis-relevant neuroimaging phenotypes

Background and Hypothesis: Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Study Design: Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Results: Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus  sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. Conclusions: These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.Radiolog

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees

Search for heavy long-lived charged R-hadrons with the ATLAS detector in 3.2 fb(-1) of proton-proton collision data at root s=13 TeV

A search for heavy long-lived charged R-hadrons is reported using a data sample corresponding to 3.2 fb−1 of proton–proton collisions at √s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider at CERN. The search is based on observables related to large ionisation losses and slow propagation velocities, which are signatures of heavy charged particles travelling significantly slower than the speed of light. No significant deviations from the expected background are observed. Upper limits at 95% confidence level are provided on the production cross section of long-lived R-hadrons in the mass range from 600 GeV to 2000 GeV and gluino, bottom and top squark masses are excluded up to 1580 GeV, 805 GeV and 890 GeV, respectively

Innovative minimally invasive options to treat drug-resistant epilepsies

International audienceDespite the regular discovery of new molecules, one-third of epileptic patients are resistant to antiepileptic drugs. Only a few can benefit from resective surgery, the current gold standard. Although effective in 50–70% of cases, this therapy remains risky, costly, and can be associated with long-term cognitive or neurological side effects. In addition, patients are increasingly reluctant to have a craniotomy, emphasizing the need for new less invasive therapies for focal drug-resistant epilepsies. Here, we review different minimally invasive approaches already in use in the clinic or under preclinical development to treat drug-resistant epilepsies. Localized thermolesion of the epileptogenic zone has been developed in the clinic using high-frequency thermo-coagulations or magnetic resonance imaging-guided laser or ultrasounds. Although less invasive, they have not yet significantly improved the outcomes when compared with resective surgery. Radiosurgery techniques have been used in the clinic for the last 20 years and have proven efficiency. However, their efficacy is not better than resective surgery, and various side effects have been reported as well as the potential risk of sudden unexpected death associated with epilepsy. Recently, a new strategy of radiosurgery has emerged using synchrotron-generated X-ray microbeams: microbeam radiation therapy (MRT). The low divergence and high-flux of the synchrotron beams and the unique tolerance to MRT by healthy brain tissues, allows a precise targeting of specific brain regions with minimal invasiveness and limited behavioral or functional consequences in animals. Antiepileptic effects over several months have been recorded in animal models, and histological and synaptic tracing analysis suggest a reduction of neuronal connectivity as a mechanism of action. The possibility of transferring this approach to epileptic patients is discussed in this review

Brain metabolism in tau and amyloid mouse models of Alzheimer's disease: An MRI study

Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for "unbiased descriptive classification", biomarkers of neurodegeneration, "N", constitute a critical component in the tri-category "A/T/N" system. Current biomarkers of neurodegeneration suffer from potential drawbacks such as requiring invasive lumbar puncture, involving ionizing radiation, or representing a late, irreversible marker. Recent human studies have suggested that reduced brain oxygen metabolism may be a new functional marker of neurodegeneration in AD, but the heterogeneity and the presence of mixed pathology in human patients did not allow a full understanding of the role of oxygen extraction and metabolism in AD. In this report, global brain oxygen metabolism and related physiological parameters were studied in two AD mouse models with relatively pure pathology, using advanced MRI techniques including T-2-relaxation-under-spin-tagging (TRUST) and phase contrast (PC) MRI. Additionally, regional cerebral blood flow (CBF) was determined with pseudocontinuous arterial spin labeling. Reduced global oxygen extraction fraction (by -18.7%, p = 0.008), unit-mass cerebral metabolic rate of oxygen (CMRO2) (by -17.4%, p = 0.04) and total CMRO2 (by -30.8%, p 0.05), suggesting normal vascular function. By contrast, in B6;SJL-Tg [APPSWE]2576Kha (APP) mice-referred to as the amyloid AD model-no brain volume reduction, as well as relatively intact brain oxygen extraction and metabolism, were found (p > 0.05). Consistent with the imaging data, behavioral measures of walking distance were impaired in Tau4R Delta K mice (p = 0.004), but not in APP mice (p = 0.88). Collectively, these findings support the hypothesis that noninvasive MRI measurement of brain oxygen metabolism may be a promising biomarker of neurodegeneration in AD.Neuro Imaging Researc