Figure 2. Amide proton transfer (APT) effects in healthy control volunteers.

(A) Amide protons ([NH]~100 mM) which resonate at +3.5 ppm from the water resonance are in constant exchange (rate~40 Hz) with surrounding bulk water ([H₂O]~110M). By selectively irradiating at the amide resonance prior to water detection, NH proton magnetization is reduced, which attenuates the detectable water signal following exchange. This effect is commonly visualized in the CEST z-spectrum (B,C), in which water signal following different radiofrequency (RF) pre-pulse offsets is shown. The lineshape is influenced by broad nuclear overhauser (NOE), T1/T2, and RF spillover effects, with small, additional attenuation apparent at +3.5 ppm owing to proton exchange. Mean (N=8) control z-spectra for (B) right and (C) left arms, along with Lorentzian fits. The squares denote acquired data whereas the solid lines denote the Lorentzian fit. The Lorentzian fit reflects information of B₁, T₁, and T₂, however not exchange and therefore provides a reference for exchange effects. (D) Both the Lorentzian APT analysis (APT_L) and Asymmetry APT analysis (APT_A) provide similar information (P<0.05) in control volunteers, however the variation in the APT_L approach is much smaller owing to a reduction of sensitivity to NOE and magnetization transfer effects on the –ppm side of the z-spectrum. Right and left arms are plotted as separate data points (16 data points total). (E) APT_L maps from a representative control volunteer (central slices covering axilla shown), which demonstrate the range of consistency between APT_L measures in right and left axilla.