Bypassing Heteronuclear MRI: Metal-Free Organosilicon Nanotracers for Background-Free Hotspot ¹H Imaging on Clinical...

Current magnetic resonance imaging (MRI) lacks contrast agents that provide background-free hotspot visualization while remaining compatible with standard clinical hardware and avoiding metal-associated toxicity. Herein, we introduce a new class of metal-free, organosilicon-based ¹H MRI hotspot tracers that are directly compatible with conventional experimental and clinical MRI systems. These tracers exploit the distinct chemical shift of silicon-shielded hydrogens (∼0 ppm) spectrally resolved from the biological ¹H background. Through architectural screening, we identified an optimized block copolymer micelle, denoted as Silicone-Generated Hotspot Tracer (SiGHT), comprising polydimethylsiloxane (PDMS) core and a hydrophilic shell. SiGHT exhibits excellent chemical and colloidal stability and enables sensitive, background-free ¹H chemical shift imaging at low concentrations (< 0.5 mg mL^-1), while being non-cytotoxic and well tolerated in vivo. The diagnostic potential of the developed probe has been demonstrated by successful ¹H MR hotspot visualization of tracer accumulation in 4T1 mouse tumors following intravenous administration. Importantly, we demonstrate robust tracer detection on both preclinical 7T and clinical 3T MRI scanners using standard ¹H MR sequences and commercial coils, underscoring its translational potential. Together, these results establish organosilicon micelles as clinically relevant, metal-free ¹H MR hotspot tracers, opening an unexplored pathway to accessible, high-sensitivity molecular imaging on existing MRI infrastructure.