Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging

Micro-computed tomography (micro-CT) facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone). Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV). We have developed a high-atomic number lanthanide (erbium) contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter \u3c 50 nm) suspended in a two-part silicone elastomer produce a perfusable fluid with viscosity of 19.2 mPa-s. Ultrasonic cavitation was used to reduce aggregate sizes to 4000 Hounsfield units, and perfusion of vessels \u3c 10  μ m in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases

Corrigendum to: Erbium-based perfusion contrast agent for small-animal microvessel imaging (Contrast Media and Molecular Imaging (2017) 2017 (7368384) DOI: 10.1155/2017/7368384)

Copyright © 2018 Justin J. Tse et al. In the article titled Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging [1], there were errors in the scale bars in Figure 3, which should be corrected as follows: (Figure Presented)

Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging

Micro-computed tomography (micro-CT) facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone). Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV). We have developed a high-atomic number lanthanide (erbium) contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter \u3c 50 nm) suspended in a two-part silicone elastomer produce a perfusable fluid with viscosity of 19.2 mPa-s. Ultrasonic cavitation was used to reduce aggregate sizes to 4000 Hounsfield units, and perfusion of vessels \u3c 10  μ m in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases

Polymer assembly encapsulation of lanthanide nanoparticles as contrast agents for in vivo micro-CT

Despite recent technological advancements in microcomputed tomography (micro-CT) and contrast agent development, pre-clinical contrast agents are still predominantly iodine-based. Higher contrast can be achieved when using elements with higher atomic numbers, such as lanthanides; lanthanides also have x-ray attenuation properties that are ideal for spectral CT. However, the formulation of lanthanide-based contrast agents at the high concentrations required for vascular imaging presents a significant challenge. In this work, we developed an erbium-based contrast agent that meets micro-CT imaging requirements, which include colloidal stability upon redispersion at high concentrations, evasion of rapid renal clearance, and circulation times of tens of minutes in small animals. Through systematic studies with poly(ethylene glycol) (PEG)-poly(propylene glycol), PEG-polycaprolactone, and PEG-poly(l-lactide) (PLA) block copolymers, the amphiphilic block copolymer PEG114-PLA53 was identified to be ideal for encapsulating oleate-coated lanthanide-based nanoparticles for in vivo intravenous administration. We were able to synthesize a contrast agent containing 100 mg/mL of erbium that could be redispersed into colloidally stable nanoparticles in saline after lyophilization. Contrast enhancement of over 250 HU was achieved in the blood pool for up to an hour, thereby meeting the requirements of live animal micro-CT

3D vessel-wall virtual histology of whole-body perfused mice using a novel heavy element stain

© 2019, The Author(s). Virtual histology – utilizing high-resolution three-dimensional imaging – is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain – derived from an established histology stain (Verhoeff’s) – is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute flushing with detergent-containing saline followed by 15-minute perfusion with the stain and a final 5-minute saline flush), animals are scanned using micro-CT. We demonstrate that the new staining protocol enables sharp delineation of the vessel walls in three dimensions over the whole body; corresponding histological analysis verified that the CT stain is localized primarily in the endothelial cells and media of large arteries and the endothelium of smaller vessels, such as the coronaries. The rapid perfusion and scanning protocol ensured that all tissues are available for further analysis via higher resolution CT of smaller sections or traditional histological sectioning

First experimental evidence of one-dimensional plasma modes in superconducting thin wires

We have studied niobium superconducting thin wires deposited onto a SrTiO$_{3}$ substrate. By measuring the reflection coefficient of the wires, resonances are observed in the superconducting state in the 130 MHz to 4 GHz range. They are interpreted as standing wave resonances of one-dimensional plasma modes propagating along the superconducting wire. The experimental dispersion law, $\omega$ versus $q$, presents a linear dependence over the entire wave vector range. The modes are softened as the temperature increases close the superconducting transition temperature. Very good agreement are observed between our data and the dispersion relation predicted by Kulik and Mooij and Sch\"on.Comment: Submitted to Physical review Letter

A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality

This document is the Accepted Manuscript version of the following article: Andy P. Siddaway, Peter J. Taylor, Alex M. Wood, and Joerg Schulz, ‘A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality’, Journal of Affective Disorders, Vol. 184: 149-159, September 2015. The final, published version is available online at: DOI: https://doi.org/10.1016/j.jad.2015.05.046Background: There is a burgeoning literature examining perceptions of being defeated or trapped in different psychiatric disorders. The disorders most frequently examined to date are depression, anxiety problems, posttraumatic stress disorder (PTSD), and suicidality. Aims: To quantify the size and consistency of perceptions of defeat and entrapment in depression, anxiety problems, PTSD and suicidality, test for differences across psychiatric disorders, and examine potential moderators and publication bias. Method:Random-effects meta-analyses based on Pearson's correlation coefficient r. Results: Forty studies were included in the meta-analysis (n=10,072). Perceptions of defeat and entrapment were strong (around r=0.60) and similar in size across all four psychiatric disorders. Perceptions of defeat were particularly strong in depression (r=0.73). There was no between-study heterogeneity; therefore moderator analyses were conducted in an exploratory fashion. There was no evidence of publication bias. Limitations: Analyses were cross-sectional, which precludes establishing temporal precedence or causality. Some of the meta-analyses were based on relatively small numbers of effect sizes, which may limit their generalisability. Conclusions: Perceptions of defeat and entrapment are clinically important in depression, anxiety problems, PTSD, and suicidality. Similar-sized, strong relationships across four different psychiatric disorders could suggest that perceptions of defeat and entrapment are transdiagnostic constructs. The results suggest that clinicians and researchers need to become more aware of perceptions of defeat and entrapmentPeer reviewedFinal Accepted Versio

Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

The optical response of Ba_{1-x}K_xBiO_3: Evidence for an unusual coupling mechanism of superconductivity?

We have analysed optical reflectivity data for Ba_{1-x}K_xBiO_3 in the far-infrared region using Migdal-Eliashberg theory and found it inconsistent with standard electron-phonon coupling: Whereas the superconducting state data could be explained using moderate coupling, \lambda=0.7, the normal state properties indicate \lambda \le 0.2. We have found that such behaviour could be understood using a simple model consisting of weak standard electron-phonon coupling plus weak coupling to an unspecified high energy excitation near 0.4 eV. This model is found to be in general agreement with the reflectivity data, except for the predicted superconducting gap size. The additional high energy excitation suggests that the dominant coupling mechanism in Ba_{1-x}K_xBiO_3 is not standard electron-phonon.Comment: 5 pages REVTex, 5 figures, 32 refs, accepted for publication in Phys. Rev.

Transcript analysis reveals a specific HOX signature associated with positional identity of human endothelial cells.

The endothelial cell has a remarkable ability for sub-specialisation, adapted to the needs of a variety of vascular beds. The role of developmental programming versus the tissue contextual environment for this specialization is not well understood. Here we describe a hierarchy of expression of HOX genes associated with endothelial cell origin and location. In initial microarray studies, differential gene expression was examined in two endothelial cell lines: blood derived outgrowth endothelial cells (BOECs) and pulmonary artery endothelial cells. This suggested shared and differential patterns of HOX gene expression between the two endothelial lines. For example, this included a cluster on chromosome 2 of HOXD1, HOXD3, HOXD4, HOXD8 and HOXD9 that was expressed at a higher level in BOECs. Quantative PCR confirmed the higher expression of these HOXs in BOECs, a pattern that was shared by a variety of microvascular endothelial cell lines. Subsequently, we analysed publically available microarrays from a variety of adult cell and tissue types using the whole "HOX transcriptome" of all 39 HOX genes. Using hierarchical clustering analysis the HOX transcriptome was able to discriminate endothelial cells from 61 diverse human cell lines of various origins. In a separate publically available microarray dataset of 53 human endothelial cell lines, the HOX transcriptome additionally organized endothelial cells related to their organ or tissue of origin. Human tissue staining for HOXD8 and HOXD9 confirmed endothelial expression and also supported increased microvascular expression of these HOXs. Together these observations suggest a significant involvement of HOX genes in endothelial cell positional identity