Minimally invasive manganese-enhanced magnetic resonance imaging for the sciatic nerve tract tracing used intra-articularly administrated dextran-manganese encapsulated nanogels

Manganese-enhanced magnetic resonance imaging (MEMRI) enables tract tracing to follow neural pathways through axonal transport. However, the method is problematic because of the high local concentrations of Mn2+ involved. We developed a tetrananogel containing a dextran-manganese complex (Dex-Mn-Gel) and applied this nanogel to rats. MnCl2 (n = 5), Dex-Mn-Gel (n = 5), or saline control (n = 3) was injected into the left knee joint of the rats (n = 13). Inflammation and tissue alterations in the knee joint were also evaluated histologically. T1-weighted images were obtained on a 7 T MRI system 24hours after the administration and compared across groups. The sciatic nerve in both legs and the surrounding musculature were used as regions of interest (ROI). No swelling was found in the knee joint infused with Dex-Mn-Gel, although prominent swelling of the knee joint was observed with MnCl2. White blood cells inside the knee joint tissue infused with the Dex-Mn-Gel were significantly less abundant (45%, P<.05) compared with the knee joints infused with MnCl2. Visualization of the sciatic nerve was significantly enhanced in rats treated with both forms of Mn2+ compared with controls (P<.01). This study is the first to attempt intra-articular administration of a manganese contrast agent into joint-capsule and demonstrate tract visualization. The Dex-Mn-Gel can be taken up by the nerve endings and reduce Mn2+ toxicity. Dex-Mn-Gel will provide a minimally invasive method for visualizing nerve tracts in vivo.