a) providing a biological sample immobilized on a substrate, wherein the biological sample is fixed;

b) contacting the biological sample with a catalyst that catalyzes de-crosslinking of molecular crosslinks in the biological sample, wherein the catalyst is a compound of formula (I),

A is selected from the group consisting of —COOH, —P(═O)(OH)₂, and S(═O)₂OH;

X¹, X², X³, and X⁴ are each independently selected from the group consisting of: CH, CR^a, and N;

each occurrence of Ra is independently selected from the group consisting of C_1-6 alkyl, C_1-6 haloalkyl, C_1-6 alkoxy, —NO₂, —NR′R″, and —C(═O)NR′R″; and

each occurrence of R′ and R″ is independently selected from the group consisting of H and C_1-6 alkyl which is optionally substituted with

 wherein n1 is an integer from 12 to 16;

c) contacting the biological sample with a nucleic acid probe that directly or indirectly binds to an RNA analyte at a location in the biological sample;

d) circularizing the nucleic acid probe to form a circularized nucleic acid probe;

e) using a polymerase to perform rolling circle amplification (RCA) using the circularized nucleic acid probe as template to generate an RCA product, optionally wherein the polymerase is a phi29 polymerase; and

f) detecting an optical signal associated with the RCA product, thereby detecting the RNA analyte at the location in the biological sample.