Carmichael’s Concise Review
real time. Importantly, this is label-free, as labels may alter the biology. SLAM microscopy was recognized as one of the recipi- ents of the Microscopy Today Innovation Awards for 2019. Historically, advances in imaging have enabled investi-
gators to visualize things in a novel manner, and therefore ask new questions that were previously not conceivable. Recently the group headed by Stephen Boppart, the same group that developed SLAM microscopy, has taken the technology a step futher. In a publication by Sixian You, Stephen Boppart and others showed that it was possible to visualize extracellular vesicles (EVs) in tis- sues and in vivo without the use of dyes, probes, or other labels [1]. Te most exciting part is that this may have clinical applications. EVs is a collective term for exosomes, microvesicles, and apop- totic bodies. Tese cell-derived particles have generated extensive interest as we learn more about how cells use them for inter- cellular communication in states of health and disease, particu- larly in cancer. It is known that cancer cells rapidly increase the production of EVs early in the disease, well before solid tumors appear. Terefore, it is thought that these EVs are important in the progression and spread of cancer. It is hypothesized that EVs released from cancer cells circulate throughout the body early in carcinogenesis, are taken up by normal cells, and direct them to upregulate their metabolism. Tis could facilitate the body to host the growing and spreading tumor. Whereas much remains to be elucidated about EVs, it is
exciting that SLAM microscopy is able to detect and visualize the presence and spatial distribution of EVs in tissue specimens and in vivo. Te recent paper by You et al., with their multimodal
optical imaging approach, identified unique optical signatures in breast cancer. Tey also showed that these signatures of EVs can be used to differentiate tumor-associated EVs from normal EVs and also indicate the aggressiveness of the tumor (Figure 1). Tey think that the autofluorescence generated by nicotin- amide adenine dinucleotide phosphate (NADPH) within the EVs, as well as the size and structural composition of the EV membrane, in turn generates a strong third-harmonic signal between lipid-aqueous interfaces. You et al. showed that these signatures from the EVs coming from various breast cancer (and normal) cell lines from rat mammary tumors and from human breast cancer specimens indicate the tumor when imaging during surgery. Tey also found signatures for normal EVs in breast tissues from normal patients. Whereas SLAM microscopy has generated stunning and
data-rich images, there also exists the potential for using these unique multi-modal optical signatures as biomarkers for both clinical diagnosis and for screening. Ongoing efforts by this team may lead to a way of detecting cancer in urine samples [2]. Tis potentially will shed new light on liquid biopsies for cancer!
References [1] S You et al., Proc Nat Acad Sci 116(48) (2019) 24012–18,
www.pnas.org/cgi/doi/10.1073/pnas.1909243116.
[2] S Boppart, personal communication. [3] Te author gratefully acknowledges Dr. Stephen Boppart for extensive assistance with this article.
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www.microscopy-today.com • 2020 July
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