Respiration gating and Bloch fitting improve pH measurements with acidoCEST MRI in an ovarian orthotopic tumor model.

We have developed a MRI method that can measure extracellular pH in tumor tissues, known as acidoCEST MRI. This method relies on the detection of Chemical Exchange Saturation Transfer (CEST) of iopamidol, an FDA-approved CT contrast agent that has two CEST signals. A log10 ratio of the two CEST signals is linearly correlated with pH, but independent of agent concentration, endogenous T1 relaxation time, and B1 inhomogeneity. Therefore, detecting both CEST effects of iopamidol during in vivo studies can be used to accurately measure the extracellular pH in tumor tissues. Past in vivo studies using acidoCEST MRI have suffered from respiration artifacts in orthotopic and lung tumor models that have corrupted pH measurements. In addition, the non-linear fitting method used to analyze results is unreliable as it is subject to over-fitting especially with noisy CEST spectra. To improve the technique, we have recently developed a respiration gated CEST MRI pulse sequence that has greatly reduced motion artifacts, and we have included both a prescan and post scan to remove endogenous CEST effects. In addition, we fit the results by parameterizing the contrast of the exogenous agent with respect to pH via the Bloch equations modified for chemical exchange, which is less subject to over-fitting than the non-linear method. These advances in the acidoCEST MRI technique and analysis methods have made pH measurements more reliable, especially in areas of the body subject to respiratory motion.