A feasibility study of photoacoustic imaging of ex vivo endoscopic mucosal resection tissues from Barrett’s esophagus patients

Background and study aims  Accurate endoscopic detection of dysplasia in patients with Barrett’s esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. Materials and methods  EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. Results  Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). Conclusion  We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.

[1]  Victor X D Yang,et al.  Endoscopic Doppler optical coherence tomography in the human GI tract: initial experience. , 2005, Gastrointestinal endoscopy.

[2]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[3]  K. Badizadegan,et al.  Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus. , 2001, Gastroenterology.

[4]  Geng Ku,et al.  Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography. , 2006, Journal of biomedical optics.

[5]  Mads S. Bergholt,et al.  In Vivo Diagnosis of Esophageal Cancer Using Image-Guided Raman Endoscopy and Biomolecular Modeling , 2011, Technology in cancer research & treatment.

[6]  Lihong V. Wang,et al.  Technical considerations in quantitative blood oxygenation measurement using photoacoustic microscopy in vivo , 2006, SPIE BiOS.

[7]  E W Steyerberg,et al.  Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists , 2007, Histopathology.

[8]  Mia K Markey,et al.  Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis , 2014, Journal of biomedical optics.

[9]  M. Solaymani-Dodaran,et al.  Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux , 2004, Gut.

[10]  A. Sonnenberg,et al.  Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia. , 2001, Gastroenterology.

[11]  Jayan Mannath,et al.  Role of endoscopy in early oesophageal cancer , 2016, Nature Reviews Gastroenterology &Hepatology.

[12]  C. Compton,et al.  High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography. , 2000, Gastrointestinal endoscopy.

[13]  Lihong V. Wang,et al.  Photoacoustic imaging in biomedicine , 2006 .

[14]  N. Brown,et al.  Angiogenesis in pre-malignant conditions , 2008, British Journal of Cancer.

[15]  Todd N. Erpelding,et al.  Deeply penetrating in vivo photoacoustic imaging using a clinical ultrasound array system , 2010, Biomedical optics express.

[16]  H Messmann,et al.  Fluorescence endoscopy for the detection of low and high grade dysplasia in ulcerative colitis using systemic or local 5-aminolaevulinic acid sensitisation , 2003, Gut.

[17]  Jan Laufer,et al.  In vitro measurements of absolute blood oxygen saturation using pulsed near-infrared photoacoustic spectroscopy: accuracy and resolution. , 2005, Physics in medicine and biology.

[18]  Brian C. Wilson,et al.  Clinical study of ex vivo photoacoustic imaging in endoscopic mucosal resection tissues , 2015, Photonics West - Biomedical Optics.

[19]  Brian C. Wilson,et al.  Autofluorescence-Based Detection of Early Neoplasia in Patients with Barrett’s Esophagus , 2004, Digestive Diseases.

[20]  Kenichi Goda,et al.  Preliminary feasibility study using a novel narrow‐band imaging system with dual focus magnification capability in Barrett's esophagus: Is the time ripe to abandon random biopsies? , 2013, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society.

[21]  Kenneth K Wang,et al.  Inter-Observer Agreement among Pathologists Using Wide-Area Transepithelial Sampling With Computer-Assisted Analysis in Patients With Barrett’s Esophagus , 2015, The American Journal of Gastroenterology.

[22]  Jan Laufer,et al.  Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration , 2007, Physics in medicine and biology.

[23]  B. Enestvedt,et al.  Sponge Sampling with Fluorescent In Situ Hybridization as a Screening Tool for the Early Detection of Esophageal Cancer , 2017, Journal of Gastrointestinal Surgery.

[24]  A. L. Reeves,et al.  Endoscopic mucosal resection. , 2000, Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates.

[25]  Robert A Weersink,et al.  Stimuli-responsive photoacoustic nanoswitch for in vivo sensing applications. , 2014, ACS nano.

[26]  A. Needles,et al.  Development and initial application of a fully integrated photoacoustic micro-ultrasound system , 2013, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[27]  Sarah Cho,et al.  Diffuse reflectance spectroscopy in Barrett’s Esophagus: developing a large field‐of‐view screening method discriminating dysplasia from metaplasia , 2014, Journal of biophotonics.

[28]  Chulhong Kim,et al.  Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. , 2011, Nature materials.

[29]  Gary Longton,et al.  Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets , 2000, American Journal of Gastroenterology.

[30]  Qifa Zhou,et al.  Catheter-based photoacoustic endoscope , 2014, Journal of biomedical optics.

[31]  R C Heading,et al.  Barrett's oesophagus. , 1987, British medical journal.

[32]  S. Arridge,et al.  Estimating chromophore distributions from multiwavelength photoacoustic images. , 2009, Journal of the Optical Society of America. A, Optics, image science, and vision.