Commonly used imaging reporters, including fluorescent and bioluminescent proteins, offer a remarkable ability to monitor gene expression in living systems. However, these optical reporters are limited by light scattering and tissue absorption, which restrict their penetration depth for imaging in living animals. In contrast, magnetic resonance imaging (MRI), using strong magnetic field and radio-frequency waves, can image deep-seated tissues and provide volumetric scans with high spatial resolution. Nevertheless, a prevalent issue with MRI genetic reporters lies in either their reliance on metal-chelates that have toxicity and bioavailability issue, or their composition of 14 genes in the case of gas vehicles, that are particularly challenging to express in mammalian cells. Our lab has developed aquaporin-1 (Aqp1) as an MRI genetic reporter, which is metal free and single gene to overcome such paradigm. Aqp1 is a channel that enhances water exchange across the plasma membrane, thereby increasing the molecular diffusivity of water in cells and tissues. This diffusivity can be captured by diffusion-weighted MRI. However, biological water diffusion is influenced by various elements of tissue structure, potentially result in high background noise in the image. To attain a high signal-to-background ratio in Aqp1 imaging and thereby enhance the sensitivity, our lab has established a differential imaging technique using Aqp1-degron fusion that stabilizes Aqp1 in a ligand-dependent manner. This technique obtains the signals originating from Aqp1 by taking the difference before and after ligand addition, which effectively separates Aqp1 signals from the surrounding tissue background and other non-specific factors that could influence water diffusion. Our goal is to enhance this established method by introducing the degron at different termini of Aqp1, aiming to achieve a more significant change in signal and further optimize the contrast.