Tissue pH measurement by magnetic resonance spectroscopy and imaging

Noninvasive techniques for measurement of tissue pH can be invaluable in assessing disease extent and response to therapy in a variety of pathological conditions, such as renal acidosis and alkalosis, and cancers. We present the details of three techniques for noninvasive measurement of tissue pH: magnetic resonance spectroscopy (MRS), magnetic resonance spectroscopic imaging (MRSI), and contrast-enhanced magnetic resonance imaging (MRI). These techniques exploit the pH-sensitivity of three different molecules, 3-aminopropylphosphonate (3-APP), (+/-) 2-imidazole-1-yl-3-ethoxycarbonyl propionic acid (IEPA), and 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrakis(acetamidomethylenephosphonic acid) (Gd-DOTA-4AmP), to examine local extracellular pH in vivo. The level of detail presented will enable nonnovice users of MRS and MRI to reproduce these methodologies in their own laboratories.