Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Radiology Department, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.
ACS Synth Biol. 2023 Oct 20;12(10):3041-3049. doi: 10.1021/acssynbio.3c00372. Epub 2023 Oct 4.
Aquaporins provide a unique approach for imaging genetic activity in deep tissues by increasing the rate of cellular water diffusion, which generates a magnetic resonance contrast. However, distinguishing aquaporin signals from the tissue background is challenging because water diffusion is influenced by structural factors, such as cell size and packing density. Here, we developed a Monte Carlo model to analyze how cell radius and intracellular volume fraction quantitatively affect aquaporin signals. We demonstrated that a differential imaging approach based on subtracting signals at two diffusion times can improve specificity by unambiguously isolating aquaporin signals from the tissue background. We further used Monte Carlo simulations to analyze the connection between diffusivity and the percentage of cells engineered to express aquaporin and established a mapping that accurately determined the volume fraction of aquaporin-expressing cells in mixed populations. The quantitative framework developed in this study will enable a broad range of applications in biomedical synthetic biology, requiring the use of aquaporins to noninvasively monitor the location and function of genetically engineered devices in live animals.
水通道蛋白通过增加细胞水扩散率来提供一种独特的方法，用于对深部组织中的遗传活性进行成像，从而产生磁共振对比。然而，由于水扩散受到细胞大小和细胞密度等结构因素的影响，因此区分水通道蛋白信号与组织背景具有挑战性。在这里，我们开发了一种蒙特卡罗模型来分析细胞半径和细胞内体积分数如何定量影响水通道蛋白信号。我们证明，基于在两个扩散时间处的信号相减的差分成像方法可以通过明确地将水通道蛋白信号与组织背景分离来提高特异性。我们进一步使用蒙特卡罗模拟来分析扩散率与表达水通道蛋白的细胞百分比之间的关系，并建立了一个映射，可以准确确定混合群体中表达水通道蛋白的细胞的体积分数。这项研究中开发的定量框架将在需要使用水通道蛋白来非侵入性地监测活动物中基因工程设备的位置和功能的生物医学合成生物学的广泛应用中发挥作用。
