Chemical exchange saturation transfer is unaffected by modest changes in pressure

ParaCEST (Paramagnetic Chemical Exchange Saturation Transfer) agents offer an unparalleled opportunity to perform quantitative molecular imaging by MRI. Agents that can alter the image contrast they generate in response to changes in local environmental parameters such as pH, glucose concentration, or lactate concentration can be used ratiometrically to quantitatively describe the local tissue environment. However, when performing such quantitative measurements it is important that the results are not confounded by changes in a second environmental parameter. Pressure in vivo is far from uniform, varying both through the respiratory cycle and from tissue to tissue (tumors, in particular, have high interstitial pressures). Since paraCEST agents have positive activation volumes, their exchange kinetics and therefore the CEST effect that they generate are necessarily related to pressure. The purpose of this investigation was to examine whether the relatively small changes in pressure exhibited in vivo could affect CEST sufficiently to confound attempts to quantify other local environmental parameters. The CEST properties of a rigid EuDOTA-tetraamide was examined at temperatures ranging from 288 to 319 K, at applied pressures ranging from 0 to 414 kPa, and presaturation (B₁) powers ranging from 524 to 935 Hz. At no point was pressure found to affect the CEST generated by this chelate, which indicates that changes in in vivo pressure is unlikely to confound the quantitative measurement of physiologically relevant parameters by paraCEST MRI. Interstitial pressure is an important physiological parameter that is often overlooked in molecular imaging. CEST is a method of generating MRI contrast that is acutely sensitive to changes in exchange and therefore possibly pressure. Variable pressure CEST experiments show that changes in interstitial pressure are unlikely to confound CEST MRI measurements.