Probing T-1-T-2 interactions and their imaging implications through a thermally responsive nanoprobe

The complex and specialised diagnostic process through magnetic resonance imaging (MRI) could be simplified with the implementation of dual T1–T2 contrast agents. T1- and T2-weighted MR are compatible modalities, and co-acquisition of contrast enhanced images in both T1 and T2 will drastically reduce artefacts and provide double-checked results. To date, efforts in the development of dual MRI probes have provided inconsistent results. Here we present the preparation and relaxometric study of a dual T1–T2 MRI probe based on superparamagnetic nanoparticles, paramagnetic Gd3+ chelates and pNIPAM (poly(N-isopropylacrylamide)), in which the distance between paramagnetic and superparamagnetic species can be modulated externally via temperature variations. Such a probe alleviates traditional nanotechnology limitations (e.g. batch to batch variability) as comparisons can be established within a single probe

Gallium and functionalized-porphyrins combine to form potential lysosome-specific multimodal bioprobes

202308 bckwAccepted ManuscriptRGCOthersThe HKBU and HKPolyU Joint Research Programme; A Royal Society International Exchange GrantPublishe

Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name 'Cy-droplet', has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a 'microbubble condensation' method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical 'triggerability' can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release

Neuron labeling with rhodamine-conjugated Gd-based MRI contrast agents delivered to the brain via focused ultrasound

Gadolinium-based magnetic resonance imaging contrast agents can provide information regarding neuronal function, provided that these agents can cross the neuronal cell membrane. Such contrast agents are normally restricted to extracellular domains, however, by attaching cationic fluorescent dyes, they can be made cell-permeable and allow for both optical and magnetic resonance detection. To reach neurons, these agents also need to cross the blood-brain barrier. Focused ultrasound combined with microbubbles has been shown to enhance the permeability of this barrier, allowing molecules into the brain non-invasively, locally and transiently. The goal of this study was to investigate whether combining fluorescent rhodamine with a gadolinium complex would form a dual-modal contrast agent that could label neurons in vivo when delivered to the mouse brain with focused ultrasound and microbubbles. Methods: Gadolinium complexes were combined with a fluorescent, cationic rhodamine unit to form probes with fluorescence and relaxivity properties suitable for in vivo applications. The left hemisphere of female C57bl/6 mice (8-10 weeks old; 19.07 ± 1.56 g; n = 16) was treated with ultrasound (centre frequency: 1 MHz, peak-negative pressure: 0.35 MPa, pulse length: 10 ms, repetition frequency: 0.5 Hz) while intravenously injecting SonoVue microbubbles and either the 1 kDa Gd(rhodamine-pip-DO3A) complex or a conventionally-used lysine-fixable Texas Red® 3 kDa dextran. The opposite right hemisphere was used as a non-treated control region. Brains were then extracted and either sectioned and imaged via fluorescence or confocal microscopy or imaged using a 9.4 T magnetic resonance imaging scanner. Brain slices were stained for neurons (NeuN), microglia (Iba1) and astrocytes (GFAP) to investigate the cellular localization of the probes. Results: Rhodamine fluorescence was detected in the left hemisphere of all ultrasound treated mice, while none was detected in the right control hemisphere. Cellular uptake of Gd(rhodamine-pip-DO3A) was observed in all the treated regions with a uniform distribution (coefficient of variation = 0.4 ± 0.05). Uptake was confirmed within neurons, whereas the probe did not co-localize with microglia and astrocytes. Compared to the dextran molecule, Gd(rhodamine-pip-DO3A) distributed more homogeneously and was less concentrated around blood vessels. Furthermore, the dextran molecule was found to accumulate unselectively in microglia as well as neurons, whereas our probe was only taken up by neurons. Gd(rhodamine-pip-DO3A) was detected via magnetic resonance imaging ex vivo in similar regions to where fluorescence was detected. Conclusion: We have introduced a method to image neurons with a dual-modal imaging agent delivered non-invasively and locally to the brain using focused ultrasound and microbubbles. When delivered to the mouse brain, the agent distributed homogeneously and was only uptaken by neurons; in contrast, conventionally used dextran distributed heterogeneously and was uptaken by microglia as well as neurons. This result indicates that our probe labels neurons without microglial involvement and in addition the probe was found to be detectable via both ex vivo MRI and fluorescence. Labeling neurons with such dual-modal agents could facilitate the study of neuronal morphology and physiology using the advantages of both imaging modalities

The health status of migrants in Australia: A review

This review summarizes the findings of studies conducted in Australia between 1980 and 2008 that focused on the health status of migrants in one or more of Australia’s National Health Priority Areas (NHPAs), identifies gaps in knowledge, and suggests further research directions. Systematic literature searches were performed on CINAHL, MediText, PsycINFO, and MEDLINE. It was found that the majority of migrants enjoy better health than the Australian-born population in the conditions that are part of the NHPAs, with the exception of diabetes. Mediterranean migrants have particularly favorable health outcomes. The migrant health advantage appears to deteriorate with increasing duration of residence. Many of the analyzed studies were conducted more than 10 years ago or had a narrow focus. Little is known about the health status of migrants with respect to a number of NHPAs, including musculoskeletal conditions and asthma.The health status of recently arrived migrant groups from the Middle East and Africa has not been explored in detail.Olga Anikeeva, Peng Bi, Janet E. Hiller, Philip Ryan, David Roder and Gil-Soo Ha