Acoustic reporter genes (ARGs) that encode air-filled gas vesicles enable ultrasound-based imaging of gene expression in genetically modified bacteria and mammalian cells, facilitating the study of cellular function in deep tissues. Despite the promise of this technology for biological research and potential clinical applications, the sensitivity with which ARG-expressing cells can be visualized is currently limited. Here we present burst ultrasound reconstructed with signal templates (BURST)—an ARG imaging paradigm that improves the cellular detection limit by more than 1,000-fold compared to conventional methods. BURST takes advantage of the unique temporal signal pattern produced by gas vesicles as they collapse under acoustic pressure above a threshold defined by the ARG. By extracting the unique pattern of this signal from total scattering, BURST boosts the sensitivity of ultrasound to image ARG-expressing cells, as demonstrated in vitro and in vivo in the mouse gastrointestinal tract and liver. Furthermore, in dilute cell suspensions, BURST imaging enables the detection of gene expression in individual bacteria and mammalian cells. The resulting abilities of BURST expand the potential use of ultrasound for non-invasive imaging of cellular functions.

编码充气气泡的声学报告基因 (ARG) 能够对转基因细菌和哺乳动物细胞中的基因表达进行基于超声的成像，从而促进深层组织中细胞功能的研究。尽管这项技术有望用于生物学研究和潜在的临床应用，但目前可以看到 ARG 表达细胞的灵敏度是有限的。在这里，我们展示了使用信号模板 (BURST) 重建的突发超声 - 一种 A​​RG 成像范例，与传统方法相比，它可将细胞检测限提高 1,000 倍以上。BURST 利用由气体囊泡产生的独特时间信号模式，因为它们在高于 ARG 定义的阈值的声压下塌陷。通过从总散射中提取该信号的独特模式，BURST 提高了超声对 ARG 表达细胞成像的灵敏度，如在小鼠胃肠道和肝脏中的体外和体内所证明的那样。此外，在稀释的细胞悬液中，BURST 成像能够检测单个细菌和哺乳动物细胞中的基因表达。由此产生的 BURST 能力扩大了超声在细胞功能非侵入性成像中的潜在用途。