Preclinical Imaging for the Translation of Innovative Nutritional Strategies: Current Applications and Future Perspectives.

Nutrient persistence, which manifests as residual deposits within parenteral and enteral delivery systems and as prolonged intraluminal retention in the gastrointestinal (GI) tract, represents a central determinant of safety and performance in clinical nutrition. This review integrates evidence across parenteral nutrition (PN), enteral nutrition (EN), and GI physiology to provide a comprehensive and mechanistic analysis of how nutrient residues arise and may affect clinically relevant outcomes among diverse nutrition delivery settings. Particular emphasis is placed on the role of imaging-based preclinical research in linking mechanistic observations of nutrient persistence with translational questions relevant to clinical nutrition. Traditional assessments of nutrient persistence have relied largely on indirect or bulk endpoints, limiting the ability to determine where nutrients remain, how long they persist, and how effectively they are cleared. Recent advances in fluorescence-based imaging provide spatially resolved and longitudinal approaches for assessing nutrient behavior in benchtop systems and preclinical models, revealing how transport dynamics and device geometry affect residue accumulation in PN systems, formulation rheology and thickener chemistry affect residue formation and microbial proliferation in EN delivery pathways, and physicochemical transformations and motility govern GI retention. This review synthesizes findings across these domains to establish an imaging-guided framework that links device engineering, formulation science, and physiological processes. Importantly, fluorescence-based imaging is presented in this review as a complementary approach rather than a replacement for established methods. Its translational value lies in its potential to generate measurable indicators of residue formation, clearance, and retention that may be linked to outcomes such as catheter performance, microbial proliferation, feeding tolerance, and nutrition delivery efficiency. Fluorescence-imaging supports the 3Rs (Replacement, Reduction, and Refinement) by enabling optimization in benchtop PN/EN models before animal studies and by allowing longitudinal assessment in GI animal models. Although challenges related to probe performance, standardization, and clinical validation remain, this approach positions nutrient persistence as a measurable and potentially modifiable parameter. Future research should prioritize standardized, outcome-linked preclinical imaging approaches that support clinical translation while promoting more efficient and responsible experimental design.