Low‐Field Nuclear Magnetic Resonance‐Based Stimulation: A Physical Framework and Research Agenda for Deep‐Tissue, Non‐Thermal Biophysical Interaction

Low-field nuclear magnetic resonance (NMR)-based stimulation is an emerging non-invasive biophysical approach for tissue modulation. Unlike optical or mechanically mediated modalities, its magnetic-field components are less constrained by tissue depth, enabling distributed exposure of deep anatomical structures. This review examines its physical principles, focusing on cyclic adiabatic passage, longitudinal relaxation time (T1), and how field parameters and tissue relaxation properties shape the spatial and temporal distribution of the applied perturbation. Clinical studies indicate a favorable safety profile together with reported improvements in pain, physical function, quality of life and related outcomes across several musculoskeletal indications, while experimental studies demonstrate modulation of inflammatory signaling, mitochondrial function, metabolism and redox-sensitive pathways. Two major mechanistic questions are identified: how a relaxation-weighted perturbation, potentially shaped by extracellular, pericellular or matrix-associated tissue properties, is transmitted to intracellular signaling pathways, and how weak non-thermal perturbations are amplified into specific biological responses. A multi-level framework is proposed to investigate how physical perturbations are distributed in tissue, transmitted to intracellular pathways, shaped by cellular state and amplified into measurable biological responses. Low-field NMR-based stimulation represents a physically plausible but mechanistically unresolved modality whose further development will depend on integrating magnetic resonance physics with systems-level biology.