MRI of Retinal Free Radical Production With Laminar Resolution In Vivo

作者:Berkowitz Bruce A*; Lewin Alfred S; Biswal Manas R; Bredell Bryce X; Davis Christopher; Roberts Robin
来源:Investigative Ophthalmology & Visual Science, 2016, 57(2): 577-585.
DOI:10.1167/iovs.15-18972

摘要

PURPOSE. Recent studies have suggested the hypothesis that quench-assisted 1/T1 magnetic resonance imaging (MRI) measures free radical production with laminar resolution in vivo without the need of a contrast agent. Here, we test this hypothesis further by examining the spatial and detection sensitivity of quench-assisted 1/T1 MRI to strain, age, or retinal cell layer-specific genetic manipulations. METHODS. We studied: adult wild-type mice; mice at postnatal day 7 (P7); cre dependent retinal pigment epithelium (RPE)-specific MnSOD knockout mice; doxycycline-treated Sod2flox/flox mice lacking the cre transgene; and alpha-transducin knockout (Gnat1(-/-)) mice on a C57Bl/6 background. Transretinal 1/T1 profiles were mapped in vivo in the dark without or with antioxidant treatment, or followed by light exposure. We calibrated profiles spatially using optical coherence tomography. RESULTS. Dark-adapted RPE-specific MnSOD knockout mice had greater than normal 1/T1 in the RPE and outer nuclear layers that was corrected to wild-type levels by antioxidant treatment. Dark and light Gnat1(-/-) mice also had greater than normal outer retinal 1/T1 values. In adult wild-type mice, dark values of 1/T1 in the ellipsoid region and in the outer segment were suppressed by 13 minutes of light. By 29 minutes of light, 1/T1 reduction extended to the outer nuclear layer. Gnat1(-/-) mice demonstrated a faster light-evoked suppression of 1/T1 values in the outer retina. In P7 mice, transretinal 1/T1 profiles were the same in dark and light. CONCLUSIONS. Quench-assisted MRI has the laminar resolution and detection sensitivity to evaluate normal and pathologic production of free radicals in vivo.

  • 出版日期2016-2