Toward clinical application of manganese-enhanced MRI of retinal function

Abstract

Purpose The application of manganese-enhanced MRI (MEMRI) to measure retinal function in humans is unclear. To begin to address this gap, we tested the hypothesis that an FDA-approved manganese-based MRI contrast agent, Teslascan, is useful for measuring functional intraretinal ionic regulation. Methods Anesthetized dark- or light-adapted male healthy Sprague–Dawley rats were infused for 30 min with 10 μmol/kg of Teslascan (clinically relevant dose; n = 5), 100 μmol/kg Teslascan ( n = 5), or saline ( n = 5). Four hours post-administration, high resolution MEMRI data were collected. Intraretinal signal intensities and enhancements were measured. Modelling was performed to estimate apparent retinal transfer constant K i and to determine optimal data acquisition parameters. Results In light-adapted rats, intraretinal enhancements responded in a dose–response manner. In addition, in the outer retina the effect of light-adaptation was to reduce significantly Mn 2+ uptake and K i compared to dark-adaptation. A non-significant change was also observed in the inner retina. Modelling shows Mn 2+ plasma concentration reaching a plateau after about 2 h. Apparent K i values for the clinically relevant dose are 3–6 × 10 −3 min −1, decreasing to 0.5–0.6 × 10 −3 min −1 at the higher dose. Intraretinal signal is almost linear with K i . Optimal TR for a spin-echo sequence is 0.4–1.4 s. Conclusion First time evidence is presented that a clinically relevant dose and route of Teslascan can be used to measure intraretinal function. The potential for future clinical application of MEMRI in a broad range of retinopathies is high.