Working principle of LACT and optimization of absorbing matrix compound for LACT and MALDI MSI. (A) Workflow for matrix deposition, laser illumination (405 nm), and chemical transfer. (B) Solid-state UV absorption spectra of different MALDI matrices coated on brain tissues. (C) The influence of transfer threshold energy on the signal intensities of venlafaxine. The transfer threshold energy was defined as the minimum real-time power of the laser (mW) necessary to achieve chemical transfer. Error bars indicate the standard deviations of 100 mass spectra acquired from ion images. (D) Comparison of MALDI MSI results of venlafaxine measured in dosed mouse brain before and after LACT treatment using different matrices. DHAP, 2,6-dihydroxyacetophenone; THAP, 2,4,6-trihydroxy-acetophenone; DAN, 1,5-diaminonapthalene; DHB, 2,5-dihydroxybenzoic acid; CHCA, α-cyano-4-hydroxycinnamic acid.