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 hours. 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 0.4-1.4s. Conclusion-Firsttime 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.

MEMRI and a nontoxic systemic dose of MnCl(2) provided an objective, noninvasive measure of an ionic deregulatory phenotype that appears useful for improved early diagnosis and treatment prognosis in a range of neurodegenerative diseases and their treatment.