Translationally Relevant Magnetic Resonance Imaging Markers in a Ferret Model of Closed Head Injury.

Pre-clinical models of traumatic brain injury (TBI) have been the primary experimental tool for understanding the potential mechanisms and cellular alterations that follow brain injury, but the human relevance and translational value of these models are often called into question. Efforts to better recapitulate injury biomechanics and the use of non-rodent species with neuroanatomical similarities to humans may address these concerns and promise to advance experimental studies toward clinical impact. In addition to improving translational aspects of animal models, it is also advantageous to establish pre-clinical outcomes that can be directly compared with the same outcomes in humans.

Meningeal and Visual Pathway Magnetic Resonance Imaging Analysis after Single and Repetitive Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA)-Induced Disruption in Male and Female Mice.

The consequences of forceful rotational acceleration on the central nervous system are not fully understood. While traumatic brain injury (TBI) research primarily has focused on effects related to the brain parenchyma, reports of traumatic meningeal enhancement in TBI patients may possess clinical significance. The objective of this study was to evaluate the meninges and brain for changes in dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) following closed-head impact model of engineered rotational acceleration (CHIMERA)-induced cerebral insult.

Spinal cord injury chronically depresses glucose uptake in the rodent model.

The pathophysiology following spinal cord injury (SCI) progresses from its lesion epicenter resulting in cellular and systemic changes acutely, sub-acutely and chronically. The symptoms of the SCI depend upon the severity of the injury and its location in the spinal cord. However, there is lack of studies that have longitudinally assessed acute through chronic in vivo changes following SCI.

Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures.

Traumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration.

Transplantation of induced neural stem cells (iNSCs) into chronically demyelinated corpus callosum ameliorates motor deficits.

Multiple Sclerosis (MS) causes neurologic disability due to inflammation, demyelination, and neurodegeneration. Immunosuppressive treatments can modify the disease course but do not effectively promote remyelination or prevent long term neurodegeneration. As a novel approach to mitigate chronic stage pathology, we tested transplantation of mouse induced neural stem cells (iNSCs) into the chronically demyelinated corpus callosum (CC) in adult mice.

Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes.

Long-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In this study, we found that mice exposed to chronic HA (5000 m for 12 weeks) exhibited deficits in learning and memory associated with hippocampal function and were linked with changes in the expression of synaptic proteins across various regions of the brain.

Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury.

Traumatic microbleeds are small foci of hypointensity seen on T2*-weighted MRI in patients following head trauma that have previously been considered a marker of axonal injury. The linear appearance and location of some traumatic microbleeds suggests a vascular origin. The aims of this study were to: (i) identify and characterize traumatic microbleeds in patients with acute traumatic brain injury; (ii) determine whether appearance of traumatic microbleeds predict clinical outcome; and (iii) describe the pathology underlying traumatic microbleeds in an index patient.

Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [F]FDG uptake.

Changes in F-fluorodeoxyglucose ([F]FDG) measured by positron emission tomography (PET) can be used for the noninvasive detection of metabolic dysfunction following mild traumatic brain injury (mTBI). This study examined the time course of metabolic changes induced by primary blast injury by measuring regional [F]FDG uptake. Adult, male rats were exposed to blast overpressure (15 psi) or sham injury, and [F]FDG uptake was measured before injury and again at 1-3 h and 7 days post-injury, using both volume-of-interest (VOI) and voxel-based analysis.

The effect of Zika virus infection in the ferret.

Although initial observations of infections with the Zika virus describe a mild illness, more recent reports show that infections by Zika result in neurotropism. In 2015, substantial congenital malformations were observed, with numerous infants born with microcephaly in Brazil. To study the underlying mechanism and effects of the disease, it is critical to find suitable animal models.

Alteration of FDG uptake by performing novel object recognition task in a rat model of Traumatic Brain Injury.

Traumatic Brain Injury (TBI) affects approximately 2.5 million people in the United States, of which 80% are considered to be mild (mTBI). Previous studies have shown that cerebral glucose uptake and metabolism are altered after brain trauma and functional metabolic deficits observed following mTBI are associated with changes in cognitive performance.

Enhanced fear memories and brain glucose metabolism (F-FDG-PET) following sub-anesthetic intravenous ketamine infusion in Sprague-Dawley rats.

Ketamine is a multimodal dissociative anesthetic, which provides powerful analgesia for victims with traumatic injury. However, the impact of ketamine administration in the peri-trauma period on the development of post-traumatic stress disorder (PTSD) remains controversial. Moreover, there is a major gap between preclinical and clinical studies because they utilize different doses and routes of ketamine administration.

Neuronal and vascular deficits following chronic adaptation to high altitude.

We sought to understand the mechanisms underlying cognitive deficits that are reported to affect non-native subjects following their prolonged stay and/or work at high altitude (HA). We found that mice exposed to a simulated environment of 5000 m exhibit deficits in hippocampal learning and memory accompanied by abnormalities in brain MR imaging. Exposure (1-8 months) to HA led to an increase in brain ventricular volume, a reduction in relative cerebral blood flow and changes in diffusion tensor imaging (DTI) derived parameters within the hippocampus and corpus callosum.

Aging alters glucose uptake in the naïve and injured rodent spinal cord.

Aging results in increased activation of inflammatory glial cells and decreased neuronal viability following spinal cord injury (SCI). Metabolism and transport of glucose is also decreased with age, although the influence of age on glucose transporter (GLUT) expression or glucose uptake in SCI is currently unknown. We therefore performed [F]Fluorodeoxyglucose (FDG) PET imaging of young (3 month) and middle-aged (12 month) rats.

Brugia malayi infection in ferrets - A small mammal model of lymphatic filariasis.

Background: The lack of effective short-course therapies for treatment of the adult stage of filarial worms is a major limitation in the global effort to eliminate lymphatic filariasis. Studies using current small mammal models of lymphatic filariasis are limited by difficulties in quantifying adult worm numbers and in assessing lymphatic anatomy and function.

Methodology/principal Findings: Here, we re-established Brugia malayi infection of ferrets as a model for lymphatic filariasis and demonstrated parasitological, immunological, and histological parallels with human infection.

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring.

The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI.

Effects of isoflurane anesthesia and intravenous morphine self-administration on regional glucose metabolism ([ F]FDG-PET) of male Sprague-Dawley rats.

Although certain drugs of abuse are known to disrupt brain glucose metabolism (BGluM), the effects of opiates on BGluM are not well characterized. Moreover, preclinical positron emission tomography (PET) studies anesthetize animals during the scan, which limits clinical applications. We investigated the effects of (i) isoflurane anesthesia and (ii) intravenous morphine self-administration (MSA) on BGluM in rats.

Repetitive Model of Mild Traumatic Brain Injury Produces Cortical Abnormalities Detectable by Magnetic Resonance Diffusion Imaging, Histopathology, and Behavior.

Noninvasive detection of mild traumatic brain injury (mTBI) is important for evaluating acute through chronic effects of head injuries, particularly after repetitive impacts. To better detect abnormalities from mTBI, we performed longitudinal studies (baseline, 3, 6, and 42 days) using magnetic resonance diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) in adult mice after repetitive mTBI (r-mTBI; daily × 5) or sham procedure. This r-mTBI produced righting reflex delay and was first characterized in the corpus callosum to demonstrate low levels of axon damage, astrogliosis, and microglial activation, without microhemorrhages.

Semiautomated Ventilation Defect Quantification in Exercise-induced Bronchoconstriction Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: A Repeatability Study.

Rationale And Objectives: This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K-means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB).

Materials And Methods: Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods.

T2 Relaxation Time Mapping of the Cartilage Cap of Osteochondromas.

Objective: Our aim was to evaluate the cartilage cap of osteochondromas using T2 maps and to compare these values to those of normal patellar cartilage, from age and gender matched controls.

Materials And Methods: This study was approved by the Institutional Review Board and request for informed consent was waived. Eleven children (ages 5-17 years) with osteochondromas underwent MR imaging, which included T2-weighted fat suppressed and T2 relaxation time mapping (echo time = 9-99/repetition time = 1500 msec) sequences.

Dynamic gadolinium-enhanced MRI of the proximal femur: preliminary experience in healthy children.

Objective: The purpose of this study is to use dynamic contrast-enhanced MRI to evaluate the perfusion characteristics of the proximal femur in the growing skeleton.

Materials And Methods: We evaluated 159 subjects (mean age, 5.67 years) who underwent a well-controlled protocol of contrast-enhanced MRI of the abdomen and hips.

Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women: results of a two-year placebo-controlled trial.

Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral density (aBMD) at the spine and hip of postmenopausal women. To gain additional insight into the effects on trabecular and cortical bone, we analyzed quantitative computed tomography (QCT) data of postmenopausal women treated with odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical Physics, University of Erlangen, Erlangen, Germany). This international, randomized, double-blind, placebo-controlled, 2-year, phase 3 trial enrolled 214 postmenopausal women (mean age 64 years) with low aBMD.

Effects of odanacatib on the radius and tibia of postmenopausal women: improvements in bone geometry, microarchitecture, and estimated bone strength.

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double-blind, placebo-controlled trial, using both quantitative computed tomography (QCT) and high-resolution peripheral (HR-p)QCT.

Age and sex dependency of cartilage T2 relaxation time mapping in MRI of children and adolescents.

Objective: T2 relaxation times on MRI are sensitive to the configuration of cartilage collagen and continually increase during aging in adults. In children, T2 relaxation times increase as a result of cartilage microstructure changes in early inflammatory arthritis. The purpose of this study was to determine age- and sex-related differences in T2 mapping of the patellar cartilage in children and adolescents during normal skeletal maturation.