Noninvasive Technique for Monitoring Drug Transport Through the Murine Cochlea using Micro-Computed Tomography
Noninvasive Technique for Monitoring Drug Transport Through the Murine Cochlea using Micro-Computed Tomography
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DOI：
10.1007/s10439-013-0816-4
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发表时间：
2013-10-01
影响因子：
3.8
通讯作者：
Borkholder, David A.
中科院分区：
文献类型：
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作者：
Haghpanahi, Masoumeh;Gladstone, Miriam B.;Borkholder, David A.
将药物局部递送至内耳具有治疗包括永久性听力损失或耳聋的内耳疾病的潜力。目前描述药物递送至内耳的药代动力学的数学模型是基于大型啮齿动物研究，在耳蜗内的几个位置进行侵入性浓度测量。因此，清除率和扩散参数的估计值是基于将有限空间分辨率的测量数据拟合到模型。为了克服这些局限性，我们开发了一种非侵入性成像技术，监测和表征药物输送的小鼠耳蜗内使用微计算机断层扫描（μ CT）。为了提高测量精度，我们进行了主题图集图像配准，以利用小鼠耳蜗的图集图像中容易获得的信息，并将来自图集的分割或标记信息传递到我们的mu CT扫描。这里提出的方法有可能量化浓度在任何点沿着充满液体的内耳鳞片。这可以允许确定增强模型的空间依赖性扩散和清除参数。
Local delivery of drugs to the inner ear has the potential to treat inner ear disorders including permanent hearing loss or deafness. Current mathematical models describing the pharmacokinetics of drug delivery to the inner ear have been based on large rodent studies with invasive measurements of concentration at few locations within the cochlea. Hence, estimates of clearance and diffusion parameters are based on fitting measured data with limited spatial resolution to a model. To overcome these limitations, we developed a noninvasive imaging technique to monitor and characterize drug delivery inside the mouse cochlea using micro-computed tomography (mu CT). To increase the measurement accuracy, we performed a subject-atlas image registration to exploit the information readily available in the atlas image of the mouse cochlea and pass segmentation or labeling information from the atlas to our mu CT scans. The approach presented here has the potential to quantify concentrations at any point along fluid-filled scalae of the inner ear. This may permit determination of spatially dependent diffusion and clearance parameters for enhanced models.