Abstract: A method of making PVA microbubbles including a functionalisation step in which PVA polymeric chains are functionalised at their ends with aldehyde groups, and a subsequent cross-linking step, in which in an air-aqueous solution emulsion with a pH between 4.5 and 5.5 the previously functionalised PVA polymeric chains cross-link by means of an acetalisation reaction, thereby forming the microbubbles. The microbubbles produced are subsequently subjected to a lyophilising step, a filling step in which medicinal gas is introduced and a restoration step of the microbubbles by adding an aqueous solution.