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Tuning the ratio of exchangeable protons in iodinated agents to improve the accuracy and detection range of pH mapping under a single low power saturation1School of Biomedical Engineering, Guangdong Provincial Key Laborary of Medical Image Processing, Southern Medical University, GuangZhou, China, 2Philips Healthcare, GuangZhou, China
Synopsis
Ratiometric chemical exchange saturation transfer MRI (acidoCEST) using two distinct exchangeable protons in iodinated agents has been widely developed for in vitro and in vivo pH mapping. The accuracy of acidoCEST and pH detection range greatly relies on the applied B1 saturation pulse and chemical properties of labile protons. In this study we try to make full use of different chemical property of two labile protons. Through finely adjusting their ratio, the accuracy and pH detection range under a single low-power B1 saturation has shown to be improved
Introduction
Tissue pH is an important indicator and diagnostic metrics in the kidney and tumor research1. Ratiometric chemical exchange saturation transfer MRI (acidoCEST) has been widely developed to measure extracelluar pH by intravascular injection of exogenous iodinated agents, such as iopamidol2 and iopromide3. There are two types of labile protons in these Iodinated agents, which have different pH-dependent exchange rate. When applying a long and high-power B1 to saturate these two labile protons, as-obtained pH accuracy in the physiological pH range were often acceptable4. Such result could also be achieved by combining two different low power saturation5. However, high power B1 saturation could induce severe concomitant MT and direct saturation problems. Meanwhile, two saturation strategy would double total acquisition time. In this study we try to make full use of different chemical property of two labile protons in iodinated agents, and seek to improve the accuracy and detection range of pH mapping under a single low power saturation by finely adjusting the ratio of exchangeable protons.Methods
Five groups of iodinated agents phantoms with total labile proton concentration fixed at 90 mM were prepared with 10mM phosphate buffered solution (PBS). The ratio of 4.2ppm and 5.6ppm labile protons in five phantom groups were adjusted to be 1:1, 1.5:1, 2;1, 3:1 and 4:1 respectively. 1:1, 1.5:1 and 2:1 groups were prepared with clinically used iopromide and iopamidol, and the other two groups were prepared with iopamidol and ioversol. The pH values were titrated to 5.5, 6, 6.5, 7, 7.5 and 8 in each group. All phantoms were kept at 37°C during imaging. CEST experiments were performed on a 7T small-bore MRI scanner (Bruker Biospec, Billerica, MA) using a 35mm birdcage transmit–receive coil. Images were acquired using a RARE sequence with a CW saturation pulse length of 5 s and saturation power(B1) at 1μT, 2μT, 3μT. A series of 59 MR frequencies were set to acquire a CEST spectrum. The acquisition parameters were as follow: TR=10s, effective TE =5ms, RARE factor=8, matrix size=80×80 and slice thickness of 5 mm. The Z-spectra were B0-corrected and inverted by equation (ST=1-MZ/M0) and fitted by multipool Lorentzian fitting.Results
Figure 1a shows representative Z-spectra obtained from the 1.5:1 group of iodinated agent phantoms under B1 of 2μT. Lorentzian fitting was applied to these Z-spectra to obtain the ST value. One result with pH=6.5 was shown in Figure1b. Figure 2 and Figure 3 show the effects of B1 saturation power and labile proton ratio on the ST value at 4.2 and 5.6 ppm. With the increased B1 power, the ST valves increased substantially and the equal ST point of 4.2 ppm and 5.6ppm shifts to a high pH. Interestingly the equal ST point shifts to a low pH range with increased labile proton ratio. This indicates that changing the labile proton ratio could get similar results as varying the B1 saturation power. Figure 2d and figure 3f show in vitro pH calibration results, based on which absolute pH was calculated from ratiometric CEST effect per pixel. Figure 4 shows the results of 1.5:1 phantom group regarding CEST ratio, measured pH and its correlation with titrated pH. All these measurement results were summarized in Table1.Discussion and Conclusion
In this work labile proton ratio in iodinated agent mixture were finely tuned with total exchangeable proton concentration fixed. We found that the labile proton ratio has similar effect on the CEST ratio as B1 saturation power does. With 4.2ppm and 5.6ppm labile proton maintained at 1.5:1, pH accuracy, detection range and sensitivity under a single saturation power of 2uT have been improved without the need of twice scanning. Based on these in vitro results, their in vivo pH mapping performance would be expected in respect to concomitant MT and direct saturation.Acknowledgements
No acknowledgement found.References
1. Estrella V., et al. Acidity Generated by the Tumor Microenvironment Drives Local Invasion. Cancer Res. 2013; 73:1524–1535.
2. Longo D.L., et al. Iopamidol as a Responsive MRI-Chemical Exchange Saturation Transfer Contrast Agent for pH Mapping of Kidneys: In Vivo Studies in Mice at 7 T. Magn. Reson. Med. 2011; 65:202–211.
3. Chen L.Q., et al. Evaluations of Extracellular pH within In Vivo Tumors Using acidoCEST MRI. Magn. Reson. Med. 2014; 72:1408–1417.
4. Ward K.M., Balaban R.S. Determination of pH Using Water Protons and Chemical Exchange Dependent Saturation Transfer (CEST). Magn. Reson. Med. 2000; 44:799–802.
5. Wu Y., et al. A Generalized Ratiometric Chemical Exchange Saturation Transfer (CEST) MRI Approach for Mapping Renal pH using Iopamidol. Magn. Reson. Med. 2017; 00:00–00.
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