Deep-tissue photoacoustic imaging of photoswitchable transgenic mouse models

Compared with visible light, near-infrared (NIR) light (700–1300 nm) is capable of deep-tissue penetration because of low tissue attenuation, and thus holds great promise for deep-tissue optical manipulation and imaging. In this work, we take advantages of the NIR Rhodopseudomonas palustris bacterial phytochrome photoreceptors (BphP1) and generate a loxP-BphP1 photoswitchable transgenic mouse model that enables Cre-dependent temporal and spatial targeting of BphP1 expression at the whole-body scale in vivo. This BphP1 phytochrome incorporates biliverdin chromophore and reversibly switches between the ground state and activated state, which enabled the light-controlled manipulation of gene expression and differential detection in photoacoustic tomography (PAT). We first validated the optogenetic performance of BphP1 that binds its engineered protein partner QPAS1 to trigger gene transcription in primary cells and living mice, and demonstrated its superior capability of deep-tissue optogenetics over the existing visible-light proteins. Then, by taking advantage of PAT's deep-tissue non-invasive imaging ability and the BphP1's photoswitching properties, we can suppress the non-switching signals from background blood and improve the molecular detection sensitivity by three orders of magnitude. This study shows the BphP1-encoded photoswitchable transgenic mouse model can be used for both NIR optogenetic manipulation and deep-tissue PAT.

Duke Scholars

Author Junjie Yao Biomedical Engineering