Gas-filled microbubbles: a novel susceptibility contrast agent for brain and liver MRI

Theme: Engineering the Future of BiomedicineGas-filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility and localized manipulation via ultrasound cavitation. However, in vivo demonstration of microbubble susceptibility effect is limited so far and microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, two types of microbubbles, custom-made albumin-coated microbubbles (AMBs) and a commercially available lipid-based clinical ultrasound contrast agent (SonoVue® ), were investigated with in vivo dynamic brain and liver MRI in Sprague-Dawley rats at 7 Tesla. Transverse relaxation rate enhancements (ΔR2*) maps were computed for brain and liver, yielding results similar to those obtained with a common MR blood pool contrast agent. These results indicate that gas-filled microbubbles can serve as an intravascular MR contrast agent at high field. Enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into microbubbles was also investigated at 7 T in vitro. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas-filled microbubble susceptibility effect can be substantially increased using iron oxides nanoparticles. With such approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Such capability has the potential to lead to real-time MRI guidance in various microbubble-based drug delivery and therapeutic applications. ©2009 IEEE.published_or_final_versionThe 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2009), Minneapolis, MN., 3-6 September 2009. In Proceedings of the 31st EMBC, 2009, p. 4049-405

Malignant and noninvasive skin tumours in renal transplant recipients.

Background. Transplant recipients require immunosuppression to prevent graft rejection. This conveys an increased risk of malignancy, particularly skin tumours. There is a need for up-to-date data for the South of England. Method. Pathology records were reviewed for 709 kidney transplant recipients on immunosuppression at our hospital from 1995 to 2008. Skin tumours were recorded/analysed. Results. Mean age at transplant was 46 years. Mean length of follow-up was 7.2 years and total follow-up was 4926 person-years. 53 (7.5%) patients (39/458 (8.5%) males and 14/251 (5.6%) females) developed ≥1 skin malignancy. Cumulative incidences of 4.0%, 7.5%, and 12.2% were observed for those with <5, <10, and ≥10 years follow-up, respectively. The rate was 45 tumours per 1000 person-years at risk. Additionally, 21 patients (3.0%) only had noninvasive tumours. 221 malignant skin tumours were found: 50.2% were SCCs, 47.1% BCCs, and 2.7% malignant melanomas. Mean years to first tumour were 5.8. Mean number of tumours per patient was 4, with mean interval of 12 months. Conclusions. Despite changes in transplantation practice during the time since the last data were published in this region, these findings are similar to previous studies. This adds to the evidence allowing clinicians to inform patients in this region of their risk

Cell number quantification of USPIO-labeled stem cells by MRI: An in vitro study

MRI plays an expanding role in stem cell therapies. The non-invasive nature and high spatial resolution of MR imaging make MR imaging a powerful tool to investigate biologic processes at the molecular and cellular level in vivo longitudinally. Quantitative detection of stem cells after transplantation may allow assessment of stem cell localization and migration, and monitoring of the therapeutic effectiveness of stem cell therapy. In this study, we present a technique for MR quantification of magnetically labeled mouse embryonic stem cells distributed or injected in agarose gel phantoms. Apparent transverse relaxation rate enhancements (ΔR2*) were measured by gradient echo sequences. The linear relationship between ΔR2* and the concentration of USPIO-labeled mouse embryonic stem cells was observed and used for quantifying cell density and cell number after injection or transplantation. The MRI acquisition and analysis protocol were validated by good agreement between actual cell numbers and MRI-estimated cell numbers over a wide range of cell numbers. This MR technique for cell number and cell density quantification is applicable to future in vivo studies. © 2006 IEEE.published_or_final_versio

Water Oxidation Catalysed by Iron Complex of N,N′-dimethyl-2,11-diaza[3,3](2,6)pyridinophane. Spectroscopy of Iron–oxo Intermediates and Density Functional Theory Calculations

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Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression.

Aim: To evaluate the effects of preventive treatment with low-level laser therapy (LLLT) on progression of dystrophy in mdx mice. Methods: Ten animals were randomly divided into 2 experimental groups treated with superpulsed LLLT (904 nm, 15 mW, 700 Hz, 1 J) or placebo-LLLT at one point overlying the tibialis anterior muscle (bilaterally) 5 times per week for 14 weeks (from 6th to 20th week of age). Morphological changes, creatine kinase (CK) activity and mRNA gene expression were assessed in animals at 20th week of age. Results: Animals treated with LLLT showed very few morphological changes in skeletal muscle, with less atrophy and fibrosis than animals treated with placebo-LLLT. CK was significantly lower (p = 0.0203) in animals treated with LLLT (864.70 U.l−1, SEM 226.10) than placebo (1708.00 U.l−1, SEM 184.60). mRNA gene expression of inflammatory markers was significantly decreased by treatment with LLLT (p<0.05): TNF-α (placebo-control = 0.51 µg/µl [SEM 0.12], - LLLT = 0.048 µg/µl [SEM 0.01]), IL-1β (placebo-control = 2.292 µg/µl [SEM 0.74], - LLLT = 0.12 µg/µl [SEM 0.03]), IL-6 (placebo-control = 3.946 µg/µl [SEM 0.98], - LLLT = 0.854 µg/µl [SEM 0.33]), IL-10 (placebo-control = 1.116 µg/µl [SEM 0.22], - LLLT = 0.352 µg/µl [SEM 0.15]), and COX-2 (placebo-control = 4.984 µg/µl [SEM 1.18], LLLT = 1.470 µg/µl [SEM 0.73]). Conclusion: Irradiation of superpulsed LLLT on successive days five times per week for 14 weeks decreased morphological changes, skeletal muscle damage and inflammation in mdx mice. This indicates that LLLT has potential to decrease progression of Duchenne muscular dystrophy

Scatter-limited conduction in printed platinum nanofilms

It is demonstrated that thin platinum films may be deposited onto smooth glass substrates using a materials printer and a propriety organometallic ink. Under opti- mised printing and subsequent thermal curing conditions, excellent film adhesion to the substrates was achieved for thicknesses of about 15 nm. The resistivity of the opti- mised films is observed to be a factor of less than 3 higher than pure bulk platinum at 300 K and exhibits a slightly smaller associated thermal coefficient of resistance. The resistivity parameters are found to be insensitive to the gaseous measurement environment which suggests that intercalated carbon regions within the films following the curing process have been largely eliminated. An analysis of the resistivity data indicates that electronic conduction is consistent with enhanced boundary scattering at granular structures that are introduced during multi-pass printing. A minimum electron mean free path of ~18 nm is deduced from the measured film topography. The presented work will find application in biosensor and fuel cell technologies.</p

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Effect of influenza on cardiorespiratory and all-cause mortality in Hong Kong, Singapore and Guangzhou.

1. Using a common modelling approach, mortality attributable to influenza was higher in the two subtropical cities Guangzhou and Hong Kong than in the tropical city Singapore. 2. The virus activity appeared more synchronised in subtropical cities, whereas seasonality of influenza tended to be less marked in the tropical city. 3. High temperature was associated with increased mortality after influenza infection in Hong Kong, whereas relative humidity was an effect modifier for influenza in Guangzhou. No effect modification was found for Singapore. 4. Seasonal and environmental factors probably play a more important role than socioeconomic factors in regulating seasonality and disease burden of influenza. Further studies are needed in identifying the mechanism behind the regulatory role of environmental factors.published_or_final_versio

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations