Toward clinical application of manganese-enhanced MRI of retinal function.

Toward clinical application of manganese-enhanced MRI of retinal function.
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DOI:
10.1016/j.brainresbull.2009.06.002
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发表时间:
2010-02-15
影响因子:
3.8
通讯作者:
Berkowitz BA
Berkowitz BA
中科院分区:
医学3区
文献类型:
--
作者:
Tofts PS;Porchia A;Jin Y;Roberts R;Berkowitz BA

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锰增强MRI(MEMRI)测量人类视网膜功能的应用尚不清楚。为了开始解决这一差距,我们测试了FDA批准的锰基MRI造影剂Teslascan可用于测量功能性视网膜内离子调节的假设。将麻醉的黑暗或光适应的雄性健康Sprague道利大鼠用10 μmol/kg Teslascan(临床相关剂量; n=5)、100 μmol/kg Teslascan(n=5)或盐水(n=5)输注30分钟。给药后4小时,收集高分辨率MEMRI数据。测量视网膜内信号强度和增强。进行建模以估计表观视网膜转移常数Ki并确定最佳数据采集参数。在光适应大鼠中,视网膜内增强以剂量-反应方式响应。此外,在视网膜外层,光适应的效果是显着降低Mn 2+摄取和Ki相比,暗适应。在内层视网膜中也观察到非显著变化。建模显示Mn 2+血浆浓度在约2小时后达到平台。临床相关剂量的表观Ki值为3-6 × 10-3 min-1,在较高剂量下降至0.5-0.6 × 10-3 min-1。视网膜内信号与Ki几乎呈线性关系。自旋回波序列的最佳TR为0.4-1.4s。首次提供证据表明,Teslascan的临床相关剂量和途径可用于测量视网膜内功能。MEMRI在广泛的视网膜病变中的未来临床应用潜力很高。
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. 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 Ki and to determine optimal data acquisition parameters. 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 Mn2+ uptake and Ki compared to dark-adaptation. A non-significant change was also observed in the inner retina. Modelling shows Mn2+ plasma concentration reaching a plateau after about 2 hours. Apparent Ki 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 Ki. Optimal TR for a spin echo sequence is 0.4-1.4s. 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.
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