Chemical exchange spin-lock (CESL) is sensitive to fast exchange metabolites. CESL is performed across a range of resonance frequency offsets. At any frequency offset, either anti-parallel or parallel spin-lock directions can be used. However, different directions can affect the z-spectrum and the magnetization transfer ratio asymmetry analysis. We used simulations and in vivo experiments to demonstrate this effect and provided theoretical analysis. We also presented preliminary results of CESL for imaging of chemical exchange associated with glycosaminoglycan (GAG) in human knee at 3.0T.