Evaluating pH in the Extracellular Tumor Microenvironment Using CEST MRI and Other Imaging Methods

Figure 13

Chemical exchange saturation transfer. (a) The number of magnetic moments aligned with the B0 static magnetic field is greater than the number aligned against the B0 field for an amide proton and a water proton. (b) Selective saturation of the MR frequency of the amide proton causes the magnetic moments to equilibrate between states. (c) Subsequent chemical exchange of the amide proton and water proton transfers some of the saturation to the water protons, causing a partial equilibration of the states for the water protons. (d) The CEST-FISP MRI protocol consists of a series of Gaussian-shaped saturation pulses repeated “” times, followed by a FISP MRI acquisition sequence. The entire process is repeated for a series of “” saturation frequencies. (e) Fourier transformation of the frequency-domain signals creates a series of “” MR images at each saturation frequency. (f) The integral of the MR signal of the tumor is plotted as a function of saturation frequency for the “” images, creating a CEST spectrum. A sum of four Lorentzian line shapes was fit to the experimental CEST spectrum to quantify the CEST effects at 5.6, 4.2, and 0.8 ppm of the CEST agent used in this example (iopromide; Ultravist, Bayer Healthcare Inc.) and also account for the direct saturation of water at 0 ppm (black line, raised 10% above the CEST spectral peaks to improve the view).