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Journal articleLeow CH, Bush N, Stanziola A, et al., 2019,
3D microvascular imaging using high frame rate ultrasound and ASAP without contrast agents: development and initial in vivo evaluation on non-tumour and tumour models
, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 66, Pages: 939-948, ISSN: 0885-3010Three-dimensional imaging is valuable to non-invasively assess angiogenesis given the complex 3D architecture of vascular networks. The emergence of high frame rate (HFR) ultrasound, which can produce thousands of images per second, has inspired novel signal processing techniques and their applications in structural and functionalimaging of blood vessels. Although highly sensitive vascular mapping has been demonstrated using ultrafast Doppler, the detectability of microvasculature from the background noise may be hindered by the low signal to noise ratio (SNR) particularly in deeper region and without the use of contrast agents. We have recently demonstrated a coherence based technique, acoustic sub-aperture imaging (ASAP), for super-contrast vascular imaging and illustrated the contrast improvement using HFR contrast-enhanced ultrasound. In this work, we provide a feasibility study for microvascular imaging using ASAP without contrast agents, and extend its capability from 2D to volumetric vascular mapping. Using an ultrasound research system and a pre-clinical probe, we demonstrated the improved visibility of microvascular mapping using ASAP in comparison to ultrafast Power Doppler (PD) on a mouse kidney, liver and tumour without contrast agent injection. The SNR of ASAP images improves in average by 10dB when compared to PD. Besides, directional velocity mappings were also demonstrated by combining ASAP with the phase information extracted from lag-1 autocorrelation. Three-dimensional vascular and velocity mapping of the mouse kidney, liver and tumour were demonstrated by stackingthe ASAP images acquired using 2D ultrasound imaging and a trigger-controlled linear translation stage. The 3D results depicted clear micro-vasculature morphologies and function
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Journal articleZhang G, Lin S, Leow CH, et al., 2019,
Quantification of vaporized targeted nanodroplets using high-frame-rate ultrasound and optics
, Ultrasound in Medicine and Biology, Vol: 45, Pages: 1131-1142, ISSN: 0301-5629Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles,are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. Particularly,the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largelyunexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, we show that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalisation of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae-and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies.
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Conference paperCooper S, Yue T, Miller P, et al., 2019,
Tripodal N-centred phosphine ligands: Towards a novel donor set for <SUP>99m</SUP>Tc and <SUP>186/188</SUP>Re radiopharmaceutical formulation
, Publisher: WILEY, Pages: S295-S296, ISSN: 0362-4803 -
Journal articlePensa E, Karpowicz R, Jabaoński A, et al., 2019,
Gold-Induced Desulfurization in a Bis(ferrocenyl) Alkane Dithiol
, Organometallics, ISSN: 0276-7333© 2019 American Chemical Society. Thiol-modified ferrocenes on gold have been archetypical model systems for many fundamental charge transfer and other studies, since both thiol-gold and ferrocene redox chemistry are considered to be well-understood. Thus unexpectedly, we found that for a representative of a new class of flexibly linked bis-ferrocenyl compounds, namely, 1-10-bis(1-ferrocenyl)decane dithiol, surface immobilization on gold failed. Instead, in the presence of gold, molecular decomposition took place, resulting in sulfur-based adlayers and well-defined molecular elimination products, for which we provide spectroscopic evidence. Careful control experiments and comparison with related ferrocene compounds provide insight into the mechanism of the observed elimination reactions, as a combined effect of the molecular structure and the nature of the gold/sulfur bond. These findings, thus, have a broader impact on the design of molecular adlayers, for example, in the context of surface functionalization in sensing or the synthesis of gold nanoparticles.
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Conference paperLeber R, Wilson L, Robaschik P, et al., 2019,
Vacuum deposition of biferrocene thin films: growth strategies for stability and tuneable magnetism
, 257th National Meeting of the American-Chemical-Society (ACS), Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727 -
Journal articleClough TJ, Jiang L, Wong K-L, et al., 2019,
Ligand design strategies to increase stability of gadolinium-based magnetic resonance imaging contrast agents
, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723- Author Web Link
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- Citations: 168
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Conference paperLeow CH, Braga M, Bush NL, et al., 2019,
Contrast vs non-contrast enhanced microvascular imaging using acoustic sub-aperture processing (ASAP): in vivo demonstration
, IEEE International Ultrasonics Symposium, IUS. 2018, Publisher: IEEE, ISSN: 1948-5719Angiogenesis plays a vital role in the progression of cancer. Non-invasive imaging techniques capable of assessing the microenvironment are therefore of clinical interest. Although highly sensitive vascular mapping has been demonstrated using ultrafast Power Doppler (PD), the detectability of microvasculature from the background noise may be hindered by the low signal-to-noise ratio (SNR) in deeper region and without the use of contrast agents. We recently developed acoustic sub-aperture processing (ASAP) processing for super-contrast vasculature imaging. This technique relies on the spatial coherence of the backscattered echoes over different acquisitions to substantially reduce the noise floor compared to the power Doppler (PD) technique. In this study, we demonstrate the feasibility of applying ASAP processing for non-contrast enhanced microvascular imaging in preclinical condition, and compare it with contrast enhanced ASAP as well as ultrafast PD. Comparing to PD, ASAP exhibit SNR improvement up to 12 dB. Higher SNR and extra visibility of smaller vessel are also demonstrated in contrast enhanced images in comparison to the non-contrast images. In conclusion, we have demonstrated the feasibility of using ASAP in vivo for non-contrast microvascular imaging, and the added benefit of using contrast agents in microvascular imaging.
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Conference paperHau Leow C, Bush NL, Stanziola A, et al., 2019,
High-contrast 3D in vivo microvascular imaging using scanning 2D ultrasound and acoutic sub-aperture processing (ASAP)
, IEEE International Ultrasonics Symposium, IUS. 2018, Publisher: IEEE, ISSN: 1948-5719Non-invasive techniques for microvascular environment assessment are invaluable for clinical diagnosis and treatment monitoring. We recently developed a super contrast processing to suppress noise background in ultrafast Power Doppler, known an acoustic sub-aperture processing (ASAP), and demonstrate using 2D contrast enhance ultrasound. However, 2D imaging is insufficient to represent the 3D complex vascular environment. We therefore extend our study to demonstrate the feasibility of our technique for volumetric imaging. A pseudo-3D imaging technique was developed and demonstrated using a research system and preclinical transducer. A mouse liver was scanned using 2D ultrafast ultrasound and a mechanical translation stage. Initial results not only demonstrated a substantial noise reduction in 2D vascular images using ASAP, but also a high contrast volumetric rendering of a mouse liver. Our technique is ready for clinical use to provide better evaluation of angiogenesis.
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Journal articleJantan KA, McArdle J, Mognon L, et al., 2019,
Heteromultimetallic compounds based on polyfunctional carboxylate linkers
, New Journal of Chemistry, Vol: 43, Pages: 3199-3207, ISSN: 1144-0546A series of homo- and hetero-nuclear, bi- and trimetallic compounds are accessible using polyfunctional linkers with carboxylic acid and alkynyl or pyridyl donor combinations. This versatile approach affords reaction at a specific donor site in each case, to accommodate both ruthenium(II) or osmium(II) units and also rhenium and gold centres. Due to the orientation of the nitrogen donors of the bipyridyl moiety in 2,2′-bipyridine-4,4′-dicarboxylic acid, the metal addition must be performed in a certain sequence due to steric considerations. One example was investigated crystallographically to add to the spectroscopic and analytical characterisation performed for all complexes. Photophysical investigations reveal the effect of incorporating second or third row transition metal centres. This approach was expanded through the use of a linker bearing both carboxylic acid and alkynyl functionalities, 1,1′-ethynylferrocene carboxylic acid. This allows initial coordination of the carboxylate donors to be followed by the formation of either an acetylide or a vinyl bridge to another metal, providing access to heterotrimetallic (FeRuOs and FeRuAu) compounds as well as a heteroheptametallic Fe3Ru2Au2 example. Preliminary electrochemical studies were performed on the latter compound.
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Journal articleMann PB, McGregor IJ, Bourke S, et al., 2019,
An atom efficient, single-source precursor route to plasmonic CuS nanocrystals
, NANOSCALE ADVANCES, Vol: 1, Pages: 522-526, ISSN: 2516-0230- Author Web Link
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- Citations: 15
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Journal articleRains JGD, ODonnelly K, Oliver T, et al., 2019,
Bicarbonate inhibition of carbonic anhydrase mimics hinders catalytic efficiency: Elucidating the mechanism and gaining insight toward improving speed and efficiency
, ACS Catalysis, Vol: 9, Pages: 1353-1365, ISSN: 2155-5435Carbonic anhydrase (CA) mimics are often studied with a focus on the hydration of CO2 for atmospheric carbon capture. Consequently, the reverse reaction (dehydration of HCO3–) has received minimal attention, so much so that the rate-limiting step of the dehydration reaction in CA mimics is currently unknown. The rate-limiting step of the hydration reaction is reported to be the bicarbonate-bound intermediate step, and thus is susceptible to product inhibition. It is not, however, clear if this inhibition is a consequence of an increase in the rate of the competing dehydration reaction or resulting from the strong affinity of bicarbonate to the mimic. To address this, insight into the dehydration reaction kinetics is needed. We therefore report the most comprehensive study of a CA mimic to date. The dehydration profile of the fastest small-molecule CA mimic, ZnL1S, was characterized, and consequently evidence for the rate-limiting step for the dehydration reaction was seen to be the bicarbonate-bound intermediate step, much like the hydration reaction. This experimental validation of the rate-limiting step was achieved through a variety of methods including NMR experiments and the effect of inhibitors, substrate concentration, and metal center on activity. With this understanding, an improvement in the favorability of the rate-limiting step was achieved, resulting in decreased bicarbonate inhibition. Thus, an increase in the mimic’s kcat for both reactions was observed, resulting in the largest rate constants of any small-molecule CA mimic reported to date (28 093 and 579 M–1 s–1 for hydration and dehydration, respectively). Enzyme-like kcat/km values were obtained for ZnL1S (5.9 × 105 M–1 s–1 for CO2 hydration), and notably there is only a difference of 2.5 orders of magnitude from the enzyme, the closest of any CA mimic reported in the literature. The results from this work can be applied to the development and improvement
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Journal articleWilkinson L, Massey E, Yue T, et al., 2019,
Cyanoferrocenes as redox-active metalloligands for coordination-driven self-assembly
, Dalton Transactions, Vol: 48, Pages: 72-78, ISSN: 1477-9234Ferrocene-based Lewis bases have found utility as metalloligands in a wide variety of applications. The coordination chemistry of cyanoferrocenes however, is underexplored. Herein, we describe a new synthetic protocol for the generation of cyanoferrocenes. The coordination chemistry of these metalloligands to [Cu(NCMe)4][PF6], [(PPh3)2Cu(NCMe)2][PF6] and [(dppf)Cu(NCMe)2][PF6] salts has been explored, providing crystallographic evidence of cluster and polymeric forms of 1,1′- and 1,2-dicyanoferrocene complexes. The stability of the complexes and ligand dissociation were found to be strongly solvent-dependent.
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Conference paperZhang G, Harput S, Shah A, et al., 2019,
Photoacoustic Super-Resolution Imaging using Laser Activation of Low-Boiling-Point Dye-Coated Nanodroplets in vitro and in vivo
, IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, Pages: 944-947, ISSN: 1948-5719- Author Web Link
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- Citations: 1
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Conference paperLahri R, Rahman M, Hernandez-Gil J, et al., 2019,
Examination of zinc ferrites vs. iron oxides as contrast agents for microwave systems
, 13th European Conference on Antennas and Propagation (EuCAP), Publisher: IEEE, ISSN: 2164-3342- Author Web Link
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- Citations: 3
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Journal articleSmith A, Blower P, Southworth R, et al., 2018,
Synthesis, gallium-68 radiolabelling and biological evaluation of a series of triarylphosphonium-functionalized DO3A chelators
, Dalton Transactions, Vol: 47, Pages: 15448-15457, ISSN: 1477-9234Radiolabelled lipophilic cations that accumulate in mitochondria according to the magnitude of the mitochondrial membrane potential can be used to report non-invasively on mitochondrial dysfunction in cardiovascular disease, cardiotoxicity, and cancer. While several such cations are already commercially available for SPECT imaging, PET offers greater promise in terms of sensitivity, resolution, and capacity for dynamic imaging and pharmacokinetic modelling. We have therefore synthesised a series of three triarylphosphonium-functionalised DO3A chelators for positron emitter gallium-68, with differing alkyl-functionalisation motifs to provide opportunities for tunable lipophilicity as a means of optimising their pharmacokinetics. To assess their capacity to report on mitochondrial membrane potential, we assessed their pharmacokinetic profiles in isolated tumour cells and isolated perfused rat hearts before and after mitochondrial depolarisation with the ionophore CCCP. All three compounds radiolabelled with over 97% RCY and exhibited log D values of between −3.12 and −1.81. In vitro assessment of the uptake of the radiotracers in cultured tumour cells showed a three-fold increase in uptake compared to unchelated [68Ga]Ga(III). However, each complex exhibited less than 1% retention in healthy hearts, which was not significantly diminished by mitochondrial depolarisation with CCCP. This preliminary work suggests that while this approach is promising, the lipophilicity of this class of tracers must be increased in order for them to be useful as cardiac or cancer imaging agents.
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Contact
Professor Nick Long
Email: n.long@imperial.ac.uk
Telephone: +44 (0)20 7594 5781
Location
501J
Molecular Sciences Research Hub
White City Campus
