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We report the studies and optimization of scintillation light measurements in an updated version of the XEMIS1 prototype for the development of the XEMIS2 camera. A novel monolithic liquid xenon Compton camera, named XEMIS2 (XEnon Medical Imaging System), attempts to achieve low-activity small-animal imaging using the 3-gamma imaging technique. This emerging detector relies on the time projection chamber technique: it will be able to perform a simultaneous detection of the three γ -rays emitted by a specific radionuclide, such as scandium-44, and to produce a good quality image with a remarkable diminution of radiopharmaceutical activity at the same time. Vacuum Ultraviolet (VUV) scintillation light and ionization charge carriers generated from the recoiling particles within the detector are detected and used to reconstruct the interaction position and deposited energy. A cost-effective self-triggering scintillation signal read-out and data acquisition (DAQ) system has been developed to achieve a continuous data read-out with negligible electronics dead time. The DAQ prototype has been installed and qualified in an updated version of the XEMIS1 detector. It reaches the performance specifications in scintillation light measurements. Moreover, scintillation signals can also be used for the virtual segmentation of the monolithic detection volume through the matching algorithm of the scintillation and ionization signals based on the Light Collection Map (LCM). This spatial pre-localization of the physical events, called the virtual fiducialization of the active volume, is used to lower the detector occupancy rate when the administered activity is increased to lessen the examination time. The XEMIS1 experimental LCMs indicate that each PMT owns an individual field of view so as to segment the active volume virtually. The preparation work for the XEMIS2 camera operation has been completed in the updated XEMIS1 detector while the XEMIS2 scintillation light measurement system is under commissioning in Nantes Centre Hospitalier Universitaire. • The XEMIS2 camera oriented to the whole-body small animal 3-gamma medical imaging is presented. • The XEMIS2 system is a monolithic liquid xenon Compton camera with a 24 cm axial field of view. • A cost-effective 16-channel self-triggering scintillation signal front-end read-out electronics named XSRETOT is reported. • The XEMIS1 experimental light collection maps can be used for the virtual segmentation of the monolithic detection volume. [ABSTRACT FROM AUTHOR]