Synthesis and Preclinical Evaluation of Fluorinated 5-Azaindoles as CB2 PET Radioligands.

Several classes of cannabinoid receptor type 2 radioligands have been evaluated for imaging of neuroinflammation, with successful clinical translation yet to take place. Here we describe the synthesis of fluorinated 5-azaindoles and pharmacological characterization and evaluation of F-radiolabeled analogues. [F] (hCB2 = 96.

Multiparametric magnetic resonance imaging for detection of pathological changes in the central nervous system of a mouse model of multiple sclerosis in vivo.

Multiple sclerosis (MS) is an autoimmune disease involving demyelination and axonal damage in the central nervous system (CNS). In this study, we investigated pathological changes in the lumbar spinal cord of C57BL/6 mice induced with progressive experimental autoimmune encephalomyelitis (EAE) disease using 9.4-T magnetic resonance imaging (MRI).

Magnetic resonance imaging anatomy of the craniovertebral ligaments: A radiological study with confirmatory dissection.

Background: Descriptions of the radiological appearance of the craniovertebral ligaments often lack detail. This study aimed to provide an accurate description of the morphology and radiological appearance of the alar and cruciform ligaments with confirmation of findings by fine dissection.

Materials And Methods: Six embalmed human cadaveric specimens were reduced to an osseoligamentous arrangement spanning the C2/3 disc to the occiput.

Neurovascular Unit Alterations in the Growth-Restricted Newborn Are Improved Following Ibuprofen Treatment.

The developing brain is particularly vulnerable to foetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant ranging from behavioural and learning disorders to cerebral palsy. No treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU).

Magnetic Resonance Spectroscopy Assessment of Brain Metabolite Concentrations in Individuals With Chronic Whiplash-associated Disorder: A Cross-sectional Study.

Objectives: Pathophysiologic mechanisms underpinning ongoing pain in whiplash-associated disorder (WAD) are not well understood, however, alterations in brain morphology and function have been observed in this population and in other chronic pain conditions. This study investigated metabolite profiles of brain regions in people with chronic WAD compared with controls.

Materials And Methods: Thirty-eight individuals with chronic WAD (mean [SD] age, 39.

Cetuximab Exhibits Sex Differences in Lymphatic Exposure after Intravenous Administration in Rats in the Absence of Differences in Plasma Exposure.

Purpose: The aim of this work was to identify whether biochemical and physiological sources of mAb pharmacokinetic sex-effects could be identified in the rat model where target-mediated disposition is avoided.

Methods: Plasma and lymphatic pharmacokinetics of the humanised anti-EGFR antibody cetuximab, along with potential physiological and biochemical drivers of pharmacokinetic sex differences, were examined in male and female rats. Cetuximab was used as a model mAb since plasma clearance is slower in female patients.

Supramolecular Fluorine Magnetic Resonance Spectroscopy Probe Polymer Based on Passerini Bifunctional Monomer.

A water-soluble fluorine magnetic resonance spectroscopy host-guest probe, P(HPA--AdamCFA), was successfully constructed from the facile synthesis of a bifunctional monomer via a quantitative Passerini reaction. Supramolecular complexation with (2-hydroxypropyl)--cyclodextrin promoted a change in the chemical environment, leading to modulation of both the relaxation properties as well as chemical shift of the fluorine moieties. This change was used to probe the supramolecular interaction by F MRI spectroscopy and give insight into fluorine probe formulation.

Computational Simulation Expands Understanding of Electrotransfer-Based Gene Augmentation for Enhancement of Neural Interfaces.

The neural interface is a critical factor in governing efficient and safe charge transfer between a stimulating electrode and biological tissue. The interface plays a crucial role in the efficacy of electric stimulation in chronic implants and both electromechanical properties and biological properties shape this. In the case of cochlear implants, it has long been recognized that neurotrophins can stimulate growth of the target auditory nerve fibers into a favorable apposition with the electrode array, and recently such arrays have been re-purposed to enable electrotransfer (electroporation)-based neurotrophin gene augmentation to improve the "bionic ear.

Computational Simulation of Array-based Electroporation in the Cochlea.

We present a computational model for predicting electric field distributions following array-based closed-loop electroporation in the cochlea. The model geometry was reconstructed from magnetic resonance images of the guinea pig cochlea and an eight-channel electrode array embedded within this geometry. The model's electrode voltage output waveform was obtained from electric potential mapping conducted in physiological solution following constant-current stimulation using the electrode array.

A USPIO doped gel phantom for R2* relaxometry.

Objective: This work describes a phantom containing regions of controlled R2* (1/T2*) values to provide a stable reference object for testing implementations of R2* relaxometry commonly used for liver and heart iron assessments.

Materials And Methods: A carrageenan-strengthened gadolinium DTPA doped agarose gel was used to enclose nine gels additionally doped with ultra-small superparamagnetic iron oxide. R2* values were determined at 1.

EphA2 as a Diagnostic Imaging Target in Glioblastoma: A Positron Emission Tomography/Magnetic Resonance Imaging Study.

Noninvasive imaging is a critical technology for diagnosis, classification, and subsequent treatment planning for patients with glioblastoma. It has been shown that the EphA2 receptor tyrosine kinase (RTK) is overexpressed in a number of tumors, including glioblastoma. Expression levels of Eph RTKs have been linked to tumor progression, metastatic spread, and poor patient prognosis.

Rorα deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue.

The Rar-related orphan receptor-α (Rorα) is a nuclear receptor that regulates adiposity and is a potential regulator of energy homeostasis. We have demonstrated that the Rorα-deficient staggerer (sg/sg) mice display a lean and obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite and brown adipose tissue serves as a mechanism to increase energy expenditure and resist obesity.

PSMA-targeting iron oxide magnetic nanoparticles enhance MRI of preclinical prostate cancer.

Aim: To evaluate the potential of newly-developed, biocompatible iron oxide magnetic nanoparticles (MNPs) conjugated with J591, an antibody to an extracellular epitope of PSMA, to enhance MRI of prostate cancer.

Materials & Methods: Specific binding to PSMA by J591-MNP was investigated in vitro. MRI studies were performed on orthotopic tumor-bearing NOD.

Resveratrol does not benefit patients with nonalcoholic fatty liver disease.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin resistance, and inflammation. Although weight loss via calorie restriction reduces features of NAFLD, there is no pharmacologic therapy. Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism.

Transgenic muscle-specific Nor-1 expression regulates multiple pathways that effect adiposity, metabolism, and endurance.

The mRNA encoding Nor-1/NR4A3 is rapidly and strikingly induced by β2-adrenergic signaling in glycolytic and oxidative skeletal muscle. In skeletal muscle cells, Nor-1 expression is important for the regulation of oxidative metabolism. Transgenic skeletal muscle-specific expression of activated Nor-1 resulted in the acquisition of an endurance phenotype, an increase in type IIA/X oxidative muscle fibers, and increased numbers of mitochondria.

Longitudinal assessment of white matter pathology in the injured mouse spinal cord through ultra-high field (16.4 T) in vivo diffusion tensor imaging.

This study examined the sensitivity of ultra-high field (16.4 T) diffusion tensor imaging (DTI; 70 μm in-plane resolution, 1mm slice thickness) to evaluate the spatiotemporal development of severe mid-thoracic contusive spinal cord injury (SCI) in mice. In vivo imaging was performed prior to SCI, then again at 2h, 1 day, 3 days, 7 days, and 30 days post-SCI using a Bruker 16.

Non-invasive monitoring of sucrose mobilization from culm storage parenchyma by magnetic resonance spectroscopy.

Because sucrose stored in mature stalks (in excess of 40% of stalk dry weight) can be wholly mobilized to supply carbon for the growth of heterotrophic tissues, we propose that sucrose mobilization requires a net sink-to-source transition that acts in toto within sett internode storage parenchyma. Based on our data we propose that mobilization of sucrose from culm storage parenchyma requires minimal investment of metabolic resources, and that the mechanism of sucrose mobilization is metabolically neutral. By magnetic resonance spectroscopy and phloem-specific tracer dyes, strong evidence was found that sucrose is mobilized from sett storage parenchyma via phloem to the growing shoot tissue.

Ventilation distribution in rats: Part 2--A comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging.

Background: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner.

Ventilation distribution in rats: Part I--The effect of gas composition as measured with electrical impedance tomography.

Unlabelled: The measurement of ventilation distribution is currently performed using inhaled tracer gases for multiple breath inhalation studies or imaging techniques to quantify spatial gas distribution. Most tracer gases used for these studies have properties different from that of air. The effect of gas density on regional ventilation distribution has not been studied.

High-field magnetic resonance imaging using solenoid radiofrequency coils.

High-resolution magnetic resonance imaging using dedicated high-field radiofrequency micro-coils at 16.4 T (700 MHz) was investigated. Specific solenoid coils primarily using silver and copper as conductors with enamel and polyurethane coatings were built to establish which coil configuration produces the best image.

Detection of endogenous iron deposits in the injured mouse spinal cord through high-resolution ex vivo and in vivo MRI.

The main aim of this study was to employ high-resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.

Ski overexpression in skeletal muscle modulates genetic programs that control susceptibility to diet-induced obesity and insulin signaling.

Transgenic mice overexpressing chicken Ski (c-Ski) have marked decrease in adipose mass with skeletal muscle hypertrophy. Recent evidence indicates a role for c-Ski in lipogenesis and energy expenditure. In the present study, wild type (WT) and c-Ski mice were challenged on a high-fat (HF) diet to determine whether c-Ski mice were resistant to diet-induced obesity.

Diffusion-weighted imaging in the prostate: an apparent diffusion coefficient comparison of half-Fourier acquisition single-shot turbo spin-echo and echo planar imaging.

Prostate cancer detection using diffusion-weighted imaging is highly affected by the accuracy of the apparent diffusion coefficient (ADC) values in an image. Echo planar imaging (EPI) is a fast sequence commonly used for diffusion imaging but has inherent magnetic susceptibility and chemical shift artefacts associated. A diffusion sequence that is less affected by these artefacts is therefore advantageous.

Cues to body size in the formant spacing of male koala (Phascolarctos cinereus) bellows: honesty in an exaggerated trait.

Determining the information content of vocal signals and understanding morphological modifications of vocal anatomy are key steps towards revealing the selection pressures acting on a given species' vocal communication system. Here, we used a combination of acoustic and anatomical data to investigate whether male koala bellows provide reliable information on the caller's body size, and to confirm whether male koalas have a permanently descended larynx. Our results indicate that the spectral prominences of male koala bellows are formants (vocal tract resonances), and show that larger males have lower formant spacing.

Magnetic resonance microimaging of the spinal cord in the SOD1 mouse model of amyotrophic lateral sclerosis detects motor nerve root degeneration.

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Current imaging studies have concentrated on areas of the brain and spinal cord that contain mixed populations of sensory and motor neurons. In this study, ex vivo magnetic resonance microimaging (MRM) was used to separate motor and sensory components by visualizing individual dorsal and ventral roots in fixed spinal cords.