Mass Spectrometry Imaging of Brain Cholesterol and Metabolites with Trifluoroacetic Acid-Enhanced Desorption Electrospray Ionization

Imaging of cholesterol and other metabolites simultaneously by ambient mass spectrometry will greatly benefit biological studies, however, it still remains challenging. Herein, by adding acid into the desorption electrospray ionization (DESI) spray solvent, we achieved simultaneous mass spectrometry imaging of cholesterol and other metabolites directly from mouse brain sections. The introduction of acid increased the signal intensity of cholesterol in mouse brain tissues by approximately 21-fold. Additionally, the present strategy provided increased signal intensities for other metabolites up to 62-fold, as well as identification of seven more metabolites (23 vs 16 for acid-enhanced DESI vs DESI). Moreover, increased corelationships for alanine as well as putrescine and spermidine with cholesterol were discovered under acid-enhanced DESI. The potential of the present strategy in the fields of biological and medical research was demonstrated by investigating the level change for cholesterol, alanine, putrescine, and spermidine in Alzheimer’s disease (AD) mouse brain