美国加州理工学院Mikhail G. Shapiro团队改进了基因表达的超灵敏超声成像技术。这一研究成果于2021年8月5日发表在国际学术期刊《自然—方法学》上。

研究人员表示，编码充满空气的气囊声学报告基因（ARG）能够对转基因细菌和哺乳动物细胞中的基因表达进行超声成像，从而促进对深层组织中细胞功能的研究。尽管这项技术在生物研究和潜在的临床应用中大有可为，但目前ARG表达的细胞能够被观察到的灵敏度是有限的。

研究人员提出了BURST（burst ultrasound reconstructed with signal templates），一种ARG成像的范式，与传统方法相比，其细胞检测极限提高了1000倍以上。BURST利用了气体小泡在超过ARG定义阈值的声压下崩溃时产生的独特时间信号模式。通过从总散射中提取这种信号的独特模式，BURST提高了超声对表达ARG的细胞成像灵敏度，这在小鼠胃肠道和肝脏的体外和体内都得到了证实。此外，在稀释的细胞悬浮液中，BURST成像能够检测单个细菌和哺乳动物细胞的基因表达。BURST由此产生的能力扩大了超声对细胞功能非侵入性成像的潜在用途。

附：英文原文

Title: Ultrasensitive ultrasound imaging of gene expression with signal unmixing

Author: Sawyer, Daniel P., Bar-Zion, Avinoam, Farhadi, Arash, Shivaei, Shirin, Ling, Bill, Lee-Gosselin, Audrey, Shapiro, Mikhail G.

Issue&Volume: 2021-08-05

Abstract: 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.

DOI: 10.1038/s41592-021-01229-w

Source: https://www.nature.com/articles/s41592-021-01229-w