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One of the risks that CO2 geological sequestration imposes on the environment is the impact of potential CO2/brine leakage on shallow groundwater. The reliability of reactive transport models predicting the response of groundwater to CO2 leakage depends on a thorough understanding of the relevant chemical processes and key parameters affecting dissolved CO2 transport and reaction. Such understanding can be provided by targeted field tests integrated with reactive transport modeling. A controlled-release field experiment was conducted in Mississippi to study the CO2-induced geochemical changes in a shallow sandy aquifer at about 50m depth. The field test involved a dipole system in which the groundwater was pumped from one well, saturated with CO2 at the pressure corresponding to the hydraulic pressure of the aquifer, and then re-injected into the same aquifer using a second well. Groundwater samples were collected for chemical analyses from four monitoring wells before, during and after the dissolved CO2 was injected. In this paper, we present reactive transport models used to interpret the observed changes in metal concentrations in these groundwater samples. A reasonable agreement between simulated and measured concentrations indicates that the chemical response in the aquifer can be interpreted using a conceptual model that encompasses two main features: (a) a fast-reacting but limited pool of reactive minerals that responds quickly to changes in pH and causes a pulse-like concentration change, and (b) a slow-reacting but essentially unlimited mineral pool that yields rising metal concentrations upon decreased groundwater velocities after pumping and injection stopped. During the injection, calcite dissolution and Ca-driven cation exchange reactions contribute to a sharp pulse in concentrations of Ca, Ba, Mg, Mn, K, Li, Na and Sr, whereas desorption reactions control a similar increase in Fe concentrations. After the injection and pumping stops and the groundwater flow rate decreases, the dissolution of relatively slow reacting minerals such as plagioclase drives the rising concentrations of alkali and alkaline earth metals observed at later stages of the test, whereas the dissolution of amorphous iron sulfide causes slowly increasing Fe concentrations.

During a carbon sequestration field study to simulate the impact of CO 2 migration on shallow groundwater chemistry, the isotope composition of dissolved inorganic carbon ( δ 13 C DIC ) and dissolved strontium ( 87 Sr/ 86 Sr) were evaluated as tracers. Dissolved CO 2 in groundwater was introduced using a closed-loop dipole-style well field situated in a shallow sand-dominated aquifer. Baseline δ 13 C DIC values, oxygen and hydrogen isotope ratios, and 87 Sr/ 86 Sr values of groundwater were established in four monitoring wells (MW-1 to 4) and one up-gradient background well (BG-1) prior to the introduction of dissolved CO 2 . Baseline groundwater δ 13 C DIC-PDB , oxygen ( δ 18 O SMOW ) and hydrogen ( δ D SMOW ) stable isotope values averaged −17, −4.1 and −19.5‰, respectively. Groundwater 87 Sr/ 86 Sr baseline values averaged 0.70840 at MW-3 and 0.70818 at MW-2. Arrival of the dissolved CO 2 plume at the monitoring wells is modeled using a 1-D analytical equation, which yields breakthrough curves with flow velocities that are consistent with prior numerical modeling estimates. The δ 13 C DIC-PDB rose to an average steady-state value of 0.16 ± 0.3‰ during the test; δ 18 O and δ D of water did not change from their baseline values. 87 Sr/ 86 Sr dropped sharply by 0.00022 at MW-3 and 0.00005 at MW-2 in the first two weeks after plume arrival at the wells, and then slowly increased toward baseline values, correlating with the behavior of dissolved Na, K, Ca, Sr and Si. Carbonate dissolution and desorption from organic matter and Fe-bearing phases at the low-pH plume front is the likely mechanism producing this behavior. The δ 13 C DIC and the 87 Sr/ 86 Sr of dissolved strontium served as excellent tracers of plume movement during this experiment.

Sequestration of carbon dioxide (CO 2 ) into deep geologic reservoirs is a potential approach for controlling the rise of CO 2 concentrations in the atmosphere. Proper characterization and permitting of storage sites is expected to include an assessment of the potential impacts of CO 2 intrusion into overlying groundwater formations. In most natural settings, the dissolution of CO 2 into groundwater will decrease the pH and can also release carbonate ligands into solution. These effects can lead to metals being mobilized from sediments through mechanisms such as ion exchange, desorption, and mineral dissolution. This laboratory-based study evaluates the extent of metal release from a groundwater system in the presence of elevated CO 2 concentrations. In particular, the research investigates the geochemical mechanisms involved in metal release, with a focus on distinguishing between pH-driven processes (e.g. carbonate dissolution and ion exchange) and carbonate-driven processes (e.g. reactions enhanced by the formation of metal–carbonate complexes). Measurements from lab-scale leaching experiments and sediment characterizations are compared to data from a concurrent controlled-release field test, where CO 2 was injected into a poorly buffered sandy groundwater formation at ∼50 m depth. Results show that the immediate effect of the introduction of CO 2 is a pH drop of ∼3 units, which leads to the quick release of some elements (e.g. Ca, Mg, Ba, Sr) by primarily pH-driven processes. The extent of metal release was different across geochemically distinct sediment types from the field site. The results suggest that it would be useful to group constituents by their pH-release trends, and to include pH and concentrations of certain indicator cations (Li, K, Na, Ba, Ca, Mg, Sr, Mn and Si) as parameters in site monitoring plans.

Gadolinium-labelled nanocomplexes offer prospects for the development of real-time, non-invasive imaging strategies to visualise the location of gene delivery by MRI. In this study, targeted nanoparticle formulations were prepared comprising a cationic liposome (L) containing a Gd-chelated lipid at 10, 15 and 20% by weight of total lipid, a receptor-targeted, DNA-binding peptide (P) and plasmid DNA (D), which electrostatically self-assembled into LPD nanocomplexes. The LPD formulation containing the liposome with 15% Gd-chelated lipid displayed optimal peptide-targeted, transfection efficiency. MRI conspicuity peaked at 4 h after incubation of the nanocomplexes with cells, suggesting enhancement by cellular uptake and trafficking. This was supported by time course confocal microscopy analysis of transfections with fluorescently-labelled LPD nanocomplexes. Gd-LPD nanocomplexes delivered to rat brains by convection-enhanced delivery were visible by MRI at 6 h, 24 h and 48 h after administration. Histological brain sections analysed by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) confirmed that the MRI signal was associated with the distribution of Gd3 + moieties and differentiated MRI signals due to haemorrhage. The transfected brain cells near the injection site appeared to be mostly microglial. This study shows the potential of Gd-LPD nanocomplexes for simultaneous delivery of contrast agents and genes for real-time monitoring of gene therapy in the brain., Graphical abstract

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion of Magnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site.

Glioblastoma multiforme (GBM) is the most common and most aggressive form of intrinsic brain tumour. Despite standard treatment involving surgical resection, chemotherapy and radiotherapy this disease remains incurable with the majority of tumours recurring adjacent to the resection cavity. Consequently there is a clear need to improve local tumour control. Convection-enhanced delivery (CED) is a practical technique for administering chemotherapeutics directly into peritumoural brain. In this study, we have tested the hypothesis that carboplatin would be an appropriate chemotherapeutic agent to administer by CED into peritumoural brain to treat GBM. Within this study we have evaluated the relationships between carboplatin concentration, duration of exposure and tumour cell kill in vitro using GBM cell lines and the relationship between carboplatin concentration and clinical and histological evidence of toxicity in vivo. In addition, we have used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to evaluate the distribution properties of carboplatin following CED into rat brain and to determine the rate at which carboplatin is cleared from the brain. Finally, we have compared the distribution properties of carboplatin and the MRI contrast agent gadolinium-DTPA in pig brain. The results of these experiments confirm that carboplatin can be widely distributed by CED and that it remains in the brain for at least 24 h after infusion completion. Furthermore, carboplatin provokes a significant GBM cell kill at concentrations that are not toxic to normal brain. Finally, we provide evidence that gadolinium-DTPA coinfusion is a viable technique for visualising carboplatin distribution using T1-weighted MR imaging.

The success of time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is dependent on effective sputtering and ionisation of analytes from the sample surface imaged. Although there have been significant advances in SIMS analysis, thanks to the advent of cluster ion beams, this has largely been in the sputtering process. Ionisation is still largely ineffective, and improvements in this direction would significantly enhance SIMS imaging. We are specifically interested in improving the capabilities of SIMS imaging for detecting metabolites (small molecular weight components of metabolism) in biological cells and tissues. Here, we report a method to enhance the signal intensities of diagnostic ions and improve SIMS imaging of metabolites using a vapour-mediated ion activation approach. Exposure of a synthetic cocktail of metabolites to ammonia vapour showed a greater than threefold increase in the deprotonated ion signals for some of the metabolites in the cocktail. However, room temperature exposure resulted in changes to the sample morphology, indicating that the sample surface was disrupted. It was possible to increase the ion yield and retain the sample morphology when the treatment was carried out at 4 °C. Application of the methodology to a plant tissue section showed the detection of signals that were not observed in the samples that were not treated. This is a promising approach that can be applied to enhance the detection of diagnostic ions for the ToF-SIMS analysis of organic and biological samples. Copyright © 2012 John Wiley & Sons, Ltd.

This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging.Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated to folic acid to create Gd.DOTA.Folate. The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonance imaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing α-FR cell line (IGROV-1), compared to an α-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS.ICP-MS confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with free folic acid inhibited binding. IGROV-1 tumors showed an increase in R (1) at 2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear enhancement on MR images. This was not observed in controls.These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.

The dissolution of CO2 in water leads to a pH decrease and a carbonate content increase in affected groundwater, which in turn can drive the mobilization of metals from sediments. The mechanisms of metal release postulated in various field and laboratory studies often differ. Drawing primarily on previously published results, we examine contrasting metal mobilization behaviors at two field tests and in one laboratory study, to investigate whether the same mechanisms could explain metal releases in these different experiments. Numerical modeling of the two field tests reveals that fast Ca-driven cation exchange (from calcite dissolution) can explain the release of most major and trace metal cations at both sites, and their parallel concentration trends. The dissolution of other minerals reacting more slowly (superimposed on cation exchange) also contributes to metal release over longer time frames, but can be masked by fast ambient groundwater velocities. Therefore, the magnitude and extent of mobilization depends not only on metal-mineral associations and sediment pH buffering characteristics, but also on groundwater flow rates, thus on the residence time of CO2-impacted groundwater relative to the rates of metal-release reactions. Sequential leaching laboratory tests modeled using the same metal-release concept as postulated from field experiments show that both field and laboratory data can be explained by the same processes. The reversibility of metal release upon CO2 degassing by de-pressurization is also explored using simple geochemical models, and shows that the sequestration of metals by resorption and re-precipitation upon CO2 exsolution is quite plausible and may warrant further attention.

Convection enhanced delivery (CED) is a method of direct injection to the brain that can achieve widespread dispersal of therapeutics, including gene therapies, from a single dose. Non-viral, nanocomplexes are of interest as vectors for gene therapy in the brain, but it is essential that administration should achieve maximal dispersal to minimise the number of injections required. We hypothesised that anionic nanocomplexes administered by CED should disperse more widely in rat brains than cationics of similar size, which bind electrostatically to cell-surface anionic moieties such as proteoglycans, limiting their spread. Anionic, receptor-targeted nanocomplexes (RTN) containing a neurotensin-targeting peptide were prepared with plasmid DNA and compared with cationic RTNs for dispersal and transfection efficiency. Both RTNs were labelled with gadolinium for localisation in the brain by MRI and in brain sections by LA-ICP-MS, as well as with rhodamine fluorophore for detection by fluorescence microscopy. MRI distribution studies confirmed that the anionic RTNs dispersed more widely than cationic RTNs, particularly in the corpus callosum. Gene expression levels from anionic formulations were similar to those of cationic RTNs. Thus, anionic RTN formulations can achieve both widespread dispersal and effective gene expression in brains after administration of a single dose by CED.

Capturing carbon dioxide (CO(2)) emissions from industrial sources and injecting the emissions deep underground in geologic formations is one method being considered to control CO(2) concentrations in the atmosphere. Sequestering CO(2) underground has its own set of environmental risks, including the potential migration of CO(2) out of the storage reservoir and resulting acidification and release of trace constituents in shallow groundwater. A field study involving the controlled release of groundwater containing dissolved CO(2) was initiated to investigate potential groundwater impacts. Dissolution of CO(2) in the groundwater resulted in a sustained and easily detected decrease of ~3 pH units. Several trace constituents, including As and Pb, remained below their respective detections limits and/or at background levels. Other constituents (Ba, Ca, Cr, Sr, Mg, Mn, and Fe) displayed a pulse response, consisting of an initial increase in concentration followed by either a return to background levels or slightly greater than background. This suggests a fast-release mechanism (desorption, exchange, and/or fast dissolution of small finite amounts of metals) concomitant in some cases with a slower release potentially involving different solid phases or mechanisms. Inorganic constituents regulated by the U.S. Environmental Protection Agency remained below their respective maximum contaminant levels throughout the experiment.

The risk of CO(2) leakage from a properly permitted deep geologic storage facility is expected to be very low. However, if leakage occurs it could potentially impact potable groundwater quality. Dissolved CO(2) in groundwater decreases pH, which can mobilize naturally occurring trace metals commonly contained in aquifer sediments. Observing such processes requires adequate monitoring strategies. Here, we use laboratory and field experiments to explore the sensitivity of time-lapse complex resistivity responses for remotely monitoring dissolved CO(2) distribution and geochemical transformations that may impact groundwater quality. Results show that electrical resistivity and phase responses correlate well with dissolved CO(2) injection processes. Specifically, resistivity initially decreases due to increase of bicarbonate and dissolved species. As pH continues to decrease, the resistivity rebounds toward initial conditions due to the transition of bicarbonate into nondissociated carbonic acid, which reduces the total concentration of dissociated species and thus the water conductivity. An electrical phase decrease is also observed, which is interpreted to be driven by the decrease of surface charge density as well as potential mineral dissolution and ion exchange. Both laboratory and field experiments demonstrate the potential of field complex resistivity method for remotely monitoring changes in groundwater quality due to CO(2) leakage.

Colchicine, a known tubulin binding agent and vascular disrupting agent, causes rapid vascular shut down and central necrosis in tumors. The binding of tubulin results in tubulin destabilization, with characteristic cell shape changes and inhibition of cell division, and results in cell death. A gadolinium(III) labeled derivative of colchicine (Gd·DOTA·Colchicinic acid) was synthesized and characterized as a theranostic agent (enabling simultaneous diagnostic/real time MRI contrast imaging). In vitro, Gd·DOTA·Colchicinic acid was shown to initiate cell changes characteristic of tubulin-destabilization in both OVCAR-3 and IGROV-1 ovarian carcinoma cell lines in vitro over a period of 24 h, while maintaining the qualities of the MR imaging tracer. In vivo, Gd·DOTA·Colchicinic acid (200 mg/kg) was shown to induce the formation of central necrosis, which was confirmed ex vivo by histology, in OVCAR-3 subcutaneous tumor xenografts, while simultaneously acting as an imaging agent to promote a significant reduction in the MR relaxation time T1 (p < 0.05) of tumors 24 h post-administration. Morphological changes within the tumor which corresponded with areas derived from the formation of central necrosis were also present on MR images that were not observed for the same colchicine derivate that was not complexed with gadolinium that also presented with central necrosis ex vivo. However, Gd·DOTA·Colchicinic acid accumulation in the liver, as shown by changes in liver T1 (p < 0.05), takes place within 2 h. The implication is that Gd·DOTA·Colchicinic acid distributes to tissues, including tumors, within 2 h, but enters tumor cells to lower T1 times and promotes cell death over a period of up to 24 h. As the biodistribution/pharmacokinetic and pharmacodynamics data provided here is similar to that of conventional colchicines derivatives, such combined data are a potentially powerful way to rapidly characterize the complete behavior of drug candidates in vivo.

Manganese-enhanced magnetic resonance imaging (MEMRI) is a novel imaging technique capable of monitoring calcium influx, in vivo. Manganese (Mn2+) ions, similar to calcium ions (Ca2+), are taken up by activated cells where their paramagnetic properties afford signal enhancement in T(1)-weighted MRI methodologies. In this study we have assessed Mn2+ distribution in mice using magnetization-prepared rapid gradient echo (MP-RAGE) based MRI, by measuring changes in T(1)-effective relaxation times (T(1)-eff), effective R(1)-relaxation rates (R(1)-eff) and signal intensity (SI) profiles over time. The manganese concentration in the tissue was also determined using inductively coupled plasma atomic emission spectrometry (ICP-AES). Our results show a strong positive correlation between infused dose of MnCl2 and the tissue manganese concentration. Furthermore, we demonstrate a linear relationship between R(1)-eff and tissue manganese concentration and tissue-specific Mn2+ distribution in murine tissues following dose-dependent Mn2+ administration. This data provides an optimized MnCl2 dose regimen for an MP-RAGE based sequence protocol for specific target organs and presents a potential 3D MRI technique for in vivo imaging of Ca2+ entry during Ca2+-dependent processes in a wide range of tissues.

Laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) was utilized in postmortem imaging of gadolinium (Gd) spatial distribution in a mouse tumor model postadministration of PEGylated Gd liposomal nanoparticles. PEGylated liposomal nanoparticles were formulated using a paramagnetic lipid incorporating Gd, in addition to a fluorescent lipid, and injected intravenously into Balb/C nude mice bearing IGROV-1 tumors. At postinjection (2 h), the tumors and selective organs were imaged by magnetic resonance imaging (MRI) and, after excision, by histology and LA–ICP–MS. The presence of Gd within tumor tissue was confirmed by LA–ICP–MS and when correlated to histology was found to be prevalent in regions of higher vascularity. The presence of Gd in the kidneys was also confirmed. We have demonstrated, in a novel manner, the use of LA–ICP–MS for the spatial detection of Gd in tumor tissue. LA–ICP–MS is valuable in providing spatio-specific information of MRI contrast agents and more importantly Gd in tumor tissue.

BACKGROUND: Dimethylmethylene blue (DMMB) has been used to photoinactivate a number of model viruses, including VSV, in RBC suspensions under conditions that preserve in vitro RBC properties during storage.23 The relative sensitivity of duck HBV (DHBV) and VSV to photoinactivation by DMMB was investigated by performing an indirect immunofluorescence assay (IFA) using primary duck hepatocyte (PDH) cultures or a standard plaque assay for the respective viruses. STUDY DESIGN AND METHODS: DMMB was added to 45-percent Hct, WBC-reduced, oxygenated AS-3 RBCs at 10-, 1-, and 0.1-μM concentrations. Samples (1-mm thick) were illuminated with 5.4-mW per cm2 of red light for 2 or 9 seconds. Unilluminated samples without DMMB or with 10 μM DMMB served as control. RESULTS: DHBV and VSV were rapidly photoinactivated by DMMB in a concentration and light-dose-dependent fashion. Neither virus was substantially inactivated by incubation with DMMB in the dark. For a given light exposure, DHBV required a concentration of DMMB one-one hundredth that of VSV to achieve approximately the same level of inactivation. CONCLUSION: DHBV appears to be considerably more sensitive than VSV to DMMB photoinactivation. Photoinactivation in 45-percent Hct RBCs can be achieved in seconds by using micromolar quantities of dye.

A novel calibration scheme for elemental analysis and imaging of biological thin sections by laser ablation ICP mass spectrometry is described. The procedure is based on spiking whole blood or blood serum with elemental standards (Sr, Gd, Pt), freezing the spiked aliquots in a customised block of CMC and sectioning by cryomicrotome. The approach is robust, convenient to implement and affords matrix matching of standards to samples in terms of chemistry and physical properties. Linear calibration and good method reproducibility was achieved with limits of detection at the ng g−1 level. Application to quantitative analysis and imaging of metallodrugs (Sr, Pt based) and MRI contrast agent (Gd based) was demonstrated.

To simulate reservoir conditions, a test tank holding 17,624 gal was built. Made of three cylindrical 10-ft × 10-ft steel sections bolted together, it is equipped with 18 observation ports and numerous fittings that permit water sampling, treatment, and temperature control. Observations have been made on juvenile salmon in water supersaturated with nitrogen.

Primary duck hepatocytes maintained in serum-free culture medium containing dimethyl sulfoxide support efficient replication of duck hepatitis B virus following infection in vitro. Cells remain susceptible to infection for at least 2 weeks after plating, allowing spread of virus via repeat cycles of infection. Up to 100% of cultured hepatocytes can be infected by prolonged exposure to high titer virus inoculum at 37 degrees. We have identified a fraction of infecting virus which binds tightly to cells at 4 degrees, presumably due to association with high affinity receptors on the hepatocyte membrane. The rate at which tightly bound virus is internalized at 37 degrees appears slow, with uptake occurring over a period of at least 16 hr.