Molecular Imaging with Aquaporin-Based Reporter Genes: Quantitative Considerations from Monte Carlo Diffusion Simulations
Year: 2023
Type: article
Abstract: 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.
Source: ACS Synthetic Biology
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, Brain and Behavior Research Foundation, Silicon Valley Community Foundation, National Alliance for Research on Schizophrenia and Depression, Chan Zuckerberg Initiative, National Institutes of Health, University of California, Santa Barbara, Materials Research Science and Engineering Center, Harvard University, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Division of Materials Research, Army Research Office, Institute for Collaborative Biotechnologies
Awards: G2045646697, G321649331, MRI: Acquisition of a Fast-scanning Confocal Microscope to Advance Biophysics, Neuroscience and Bioengineering Research and Training, G325663671, A genetically encoded MRI reporter for noninvasive imaging of activity-dependent gene expression in neurons, G4250104368, G4950536974, G5681652957, G608057831, G6512159266, G65411870, Materials Research Science and Engineering Center at UCSB, G7400121136, G7437795455, G7452299184, G7511209169, G8415477955, Engineering fluorescence and magnetic resonance reporter genes for imaging biological function in hypoxic cells and in vivo, Engineering a calcium reporter gene for magnetic resonance imaging of neural activity, Metal-free, genetically encoded reporters for calcium recording with MRI
OpenAlex ID: W4387344737