Fluorescence In Vivo Endomicroscopy
Figure 1: Laparoscopic imaging of a pig with FIVE. (A) Instrument setup. (B) Histoarchitecture of microvilli in the ileum. Contrast agent, i.v. fluorescein. (C) Micro- vasculature of the liver. Contrast agent, i.v. fluorescein. (D) Liver capsule. Contrast agent, topical 0.5% acriflavine. (E) Blood vessels imaged from the serosal surface of the bladder. Contrast agent, i.v. fluorescein. (F) Perineum. Contrast agent, topical 0.5% acriflavine. Scale bars=100 μm.
with fluorophore tagged EGFR antibodies [4]. FIVE imaging confirmed various degrees of EGFR expression in different cell lines, as well as in living mice. Similar studies targeting vascu- lar endothelial growth factor (VEGF) in colorectal cancer has also been reported, suggesting that FIVE can contribute to the identification of lesions and predict response to targeted treat- ment [5]. Moreover, these studies also demonstrated the use of FIVE as an in vivo immunohistochemical/molecular imaging apparatus in preclinical studies. Gastrointestinal imaging. FIVE has been extensively
used in imaging gastrointestinal tissue [6–8] and clinically proven to successfully characterize Barrett’s esophagus [9], gastritis [10], Helicobacter pylori infection [11], intestinal meta- plasia [12], gastric hyperplastic and adenomatous polyps [13], colon polyps, and rectal cancers [14–15]. Many clinical studies have reported FIVE-integrated endomicroscopes (also known as Pentax ISC-1000 and eCLE) as a highly accurate tool for detection of Barrett’s esophagus [16] and neoplasia, greatly reducing the needed number of biopsies [17–19]. Tough other CLEs can also detect Barrett’s esophagus, FIVE has higher inter-rater agreement and accuracy [20]. Many other studies have also reported the efficiency of FIVE in detecting Barrett’s esophagus and esophageal cancer as well as imaging its virtual
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histology [21–22]. Similarly, FIVE offers great potential in sur- veillance of patients having diffuse gastric mucosal alterations, with high prevalence of gastric cancer where random biopsies are suboptimal [23]. FIVE has been extensively used for detect- ing gastric cancer with 99% accuracy in diagnosis of high-grade neoplasia and superficial cancer [24]. Tis study also reported differentiated gastric cancerous mucosa with hypervascularity and various caliber microvessels with irregular shapes. Undif- ferentiated gastric cancers disclosed hypovascularity and irregular, short branch vessels. In addition to detecting gastric cancers, FIVE was also efficient in detecting residual cancer following endoscopic submucosal dissection [25]. Similar to clinical studies, FIVE has been employed for imaging gastric mucosa in research dogs [26], providing high-quality histology equivalent images of gastric mucosa, and allowing the assess- ment of cytoplasmic and microvascular features using i.v. fluo- rescein and topical application of acriflavine (Figure 2). Tese authors were also able to diagnose and monitor infection of canines with Helicobacter and monitored the effectiveness of treatment. FIVE has also been used for imaging intestinal mucosa.
In fact, serendipitous observations, made in patients with endomicroscopy, have answered key questions and spawned
www.microscopy-today.com • 2021 May
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