Understanding lipid digestion is crucial for health strategy development in managing energy intake and nutrient bioavailability. Lipolysis kinetics can be studied by assessing the chemical composition, which requires sample purification and lipid extraction. For online monitoring of lipolysis, non-invasive methods like MRI remain to be developed. A recent study suggested that the MRI water-fat separation method enables quantifying undigested lipids, but not lipolytic products (Musse et al., 2023). To find out the mechanism behind this and to assess the feasibility of monitoring lipolysis using this approach, the lipid quantification by MRI during in vitro intestinal digestion of a commercial fresh cream was supplemented by thin-layer chromatography (TLC) for quantifying lipolysis and Time Domain (TD)-NMR for characterization in details of transverse (T2) relaxation times. The TLC analysis showed that around 96% of the triacylglycerols (TAG) was hydrolysed into lipolytic products (including free fatty acids (FFA), diglycerides (DAG), and monoglycerides (MAG)) after the in vitro intestinal digestion. The MRI results demonstrated that the loss of lipid signal correlated with the degree of lipolysis of the samples. The TD-NMR results showed a remarkable difference in the T2 of undigested lipids (~120 ms; in this study, mostly TAG) and that of lipolytic products (~2 ms; FFA, DAG, and MAG). The very short T2 of lipolytic products is likely due to the semi-crystalline structures they formed with bile salts (micelles, vesicles, liposomes, etc.) and they were suspended in the aqueous phase. Notably, The MRI water-fat separation method is not able to capture the signal from such fast-relaxing protons (short T2), which explains why the signal of lipolysis products cannot be detect. Nonetheless, the MRI method proves effective in quantifying lipolysis by monitoring the decreasing amount of undigested lipids during in vitro digestion. Moreover, the MRI imaging parameters could even be optimized to acquire rapid mapping on lipolysis in 13 seconds (within a breath hold), opening up many opportunities for future in vivo applications. In conclusion, magnetic resonance techniques are potential methods for investigating digestion processes. MRI water-fat separation method can quantify the lipolysis of cream during in vitro digestion and may serve as a promising method in studying real-time lipolysis of other foods in the gastrointestinal digestive tract, both in vitro and in vivo.