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Magnetic resonance imaging measures the intensities of the water protons inside the human body to give the spatial distribution and reveal internal structures. The signal intensity depends on the amount of water in a particular place and the proton longitudinal and transverse magnetic spin relaxation times (T). The values of T, in turn, are dependent on a number of factors such as the tissue type and blood flow. For instance, tumours can be detected by the different T values of the dead and living tissues. The changes in signal intensity can be small and difficult to visualise, so a series of contrast agents have been developed to enhance them. They are generally based on gadolinium because it is one of the more paramagnetic metals, so it polarises water molecules around it and leads to accelerated spin relaxation. The image contrast between tissues of different water content is enhanced and the fine tissue structure is revealed. Five contrast agents dominate the shelves in the MRI storeroom. They are all based on complexes of Gd with linear or cyclic chelating agents based on polyamino carboxylic acids. The three main linear agents are Magnevist (Gd-DTPA), Omniscan (Gd-DTPA-BMA) and Multihance (Gd-BOPTA), containing diethylenetriaminepentaacetic acid or its derivatives. The two cyclic agents in common use are Dotarem (Gd-DOTA) and Gadovist (Gd-BT-DO3A) and they are based on tetraazacyclododecane acetates. In practice, the agents are administered in high dosages equivalent to about 1.2 g Gd per scan. The compounds are not metabolised in the body and are excreted unchanged. Their high polarity and good water solubility coupled with their poor biodegradability ensure that they have long lifetimes in water. In fact, it has been reported that they are not very effectively removed from waste water treatment plants and tend to pass right through. In Germany, total Gd emission by hospitals and practices has been estimated at more than 1,100 kg/year. So, scientists there decided to develop a method of measuring the contrast agents in water to see how effective the treatment process is. Uwe Karst and co-workers at the Westfalische Wilhelms University of Munster had previously designed an LC/MS method using hydrophilic interaction chromatography (HILIC) and electrospray ionisation. HILIC provided high separation efficiency for the five Gd contrast agents but electrospray would not be sufficiently sensitive for Gd speciation in wastewater. So, they retained the HILIC component but replaced the detector with an ICPMS system. This way, the Gd complexes can be separated and quantified individually and the ICPMS system can also be used to measure the total Gd content of water samples. A zwitterionic HILIC column was used with an isocratic mobile phase of aqueous acetonitrile containing ammonium formate and formic acid. The five contrast agents were separated and eluted within 25 minutes and passed to the mass spectrometer. A makeup flow of oxygen was supplied to the plasma gas after ignition to prevent excessive deposition of organic carbon in the source due to the high organic content of the mobile phase. Other precautions had to be taken too. Untreated glassware irreversibly adsorbed the analytes from solution, so had to be silylated in advance to prevent losses. Also the ICPMS signals declined gradually and coherently for all analytes, so the control solution was analysed after every second measurement. Quantitation was achieved by normalising a sample peak area to the mean peak area from the preceding and succeeding control samples. These conditions led to detection limits of 1 and 0.2 nmol for HILIC/ICPMS and ICPMS, respectively, with equivalent quantitation limits of 3.3 and 0.66 nmol. Calibration was linear from 1 nmol to 1 µmol. Wastewater effluent was collected from two tower buildings of a hospital with a daily throughput of 15-30 MRI patients using Gadovist and Magnevist Gd contrast agents. Average concentrations from one tower were 0.64 nmol (0.10 µg/L), which is below the HILCI/ICPMS detection limit but the levels from the other tower were about 30-fold greater. Speciation analysis revealed that the principle Gd agent present was Gadovist. Samples were also drawn from a sewage pit directly downstream from the hospital. Levels of gadovist were of the same order as from the tower, so dilution effects were considered negligible. Finally, samples were taken at different stages of the wastewater treatment plant that took in effluent from all hospitals and radiological practices in the region. Three Gd agents were detected and measured: the active compounds of Multihance, Dotarem and Gadovist, with Gadovist the most abundant. That finding fits with practice as this contrast agent is the primary agent administered in four out of five hospitals and two radiological practices. The levels of the agents were reduced continuously throughout the wastewater treatment process but they were still present in the final "clean" water at about 40% of the input level, so there is room for improvement in the purification process. The new HILIC/ICPMS with its superior performance and improved detection limits could be used to monitor the behaviour of the different Gd complexes during wastewater treatment to allow for better removal and purification and the provision of a cleaner output. Related links:
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd. |
Credit: NCI Frederick |
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