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Hybrid optical and optoacoustic endoscope for esophageal tracking.

Periodic Reporting for period 2 - ESOTRAC (Hybrid optical and optoacoustic endoscope for esophageal tracking.)

Reporting period: 2018-07-01 to 2019-08-31

More than 450,000 people are diagnosed with esophageal cancer (EC) each year and around 400,000 die annually from the disease. In the past three decades, EC incidence rates increased by six fold, making EC the fastest rising cancer in the Western World. This severe increase is closely associated with modern lifestyle and its concomitants such as alcohol consumption, higher age, obesity, and, in particular, a pre-cancerous condition called Barrett’s esophagus (BE), affecting around 10 million people in the Western countries. All these predispositions may lead to EC if not detected and treated early on.
Unfortunately, EC is often detected late leading to the high mortality rates mentioned above. In fact, the 5-year survival rate is only 10% if detected late while it significantly increases to 90% upon early diagnosis. The current situation of late EC detection is largely based on the lack of adequate detection methods.
In recent times, EC detection typically relies on white-light endoscopy (WLE), i.e. the visual inspection of the esophagus through an optical system (endoscope) and subsequent pathological analysis of biopsied samples. Human vision, however, is insensitive to detecting early disease and lacks specificity and staging ability, compromising disease prognosis. Due to WLE limitations, random biopsies are often prescribed to improve the chances of detecting early disease and tumor staging. Nevertheless, random tissue sampling is sub-optimal as it is slow, covers less than 0.1% of the total esophageal area, is prone to sampling errors and thus, is often inaccurate and may miss lesions.
Consequently, novel technologies for early EC detection are urgently needed. Within the EU-sponsored project ESOTRAC, engineers and clinicians from 5 different countries collaborate to significantly improve the detection of early-stage EC. The interdisciplinary research team develops an innovative endoscope that combines sensing of pathophysiological tissue signatures resolved by multi-spectral optoacoustic tomography (MSOT) with morphological disease parameters provided by optical coherence tomography (OCT). The novel endoscope will not require patient sedation and will have superior qualities in detecting early stages of EC compared to WLE, e.g. by not only inspecting the esophageal surface but screening for abnormalities hidden inside the tissue. The hybrid endoscope will generate three dimensional images of the esophagus at high resolution, allowing physicians to inspect the entire esophagus wall and to detect early onset of cancer within the mucosa/submucosa, which in turn, will reduce unnecessary biopsies.
Moreover, the socio-economic impact of ESOTRAC will be immense. Treating late disease incurs average costs of €130,000 per patient putting esophageal cancer amongst the most expensive treatments in oncology today. A 5% shift from late-detections to early-detections would result in €2.7 billion savings; with a 10% shift, this number would rise to €5.4 billion.
Early in the project, the consortium defined and refined the requirements, settings, and physical properties of the technological components and of the endoscope itself, with most components being manufactured during the second project period. ESOTRAC partners discussed various biocompatible materials as well as alternate configurations of hardware and already tested their suitability for incorporation into the hybrid endoscope. As a first step, a portable laboratory-based prototype combining MSOT and OCT was designed for the initial measurements and was installed at the Medical University of Vienna. The results of the ongoing tests feed into the optimization cycle for the final endoscope. An experiment on imaging human esophageal resection samples was performed at the University of Cambridge hospital to gather first insights on logistics, procedures and image quantification.
In parallel, the ESOTRAC team constantly improved the design of the final hybrid endoscope. Size, shape, materials, and optical characteristics of components were selected to enable successful clinical application of the endoscope. The immediate goal now will be to assemble the first prototype and to test it in excised esophageal specimen and ultimately, in patients.
As raising awareness is of outmost importance, the ESOTRAC consortium created a website ( to inform the general public, scientists and clinicians about the project goals and most recent developments. ESOTRAC distributed a press release, flyers, and brochures to relevant stakeholders and created a YouTube video entitled “Future of Biomedical Imaging: ESOTRAC”. An article about ESOTRAC was published in the Physics World Magazine and ESOTRAC took part in an exhibition to inform the general public. Recent outreach activities to the scientific community include, for instance, a workshop at the European Molecular Imaging Meeting in San Sebastian/ Spain in 2018 as well as oral and poster presentations at international conferences plus pitch events by the exploitation manager. To top it off, ESOTRAC members published seven scientific publications in high-ranking journals.
At the end of the four-year funding period, the ESOTRAC consortium will present a market-ready hybrid endoscope with unparalleled capabilities to detect early stages of EC. Since the key technologies have never been combined before in an endoscopic setting, a number of technical components need to be developed and miniaturized within ESOTRAC. By nature, this bears a huge innovation potential not only for ESOTRAC per se but also for other clinical applications and as such represents enormous progress beyond the state of the art.
Moreover, the ESOTRAC consortium is expecting to secure new patents in the fields of laser light sources, ultrasound detectors, data analysis software including a ground-breaking portfolio of new imaging features for diagnostic applications, and last but not least the novel endoscope design.
From a medical point of view, WLE examinations are currently performed under sedation requiring highly trained personnel and specialized facilities. – Thus, rural residents may have a disadvantage compared to urban populations. By offering cross-sectional imaging and quantification without requiring sedation, the novel endoscope can improve upon objective metrics for disease detection, enabling precision medicine and standardizing the quality of healthcare in EC and other diseases, offered by specialized centers and peripheral sites alike. In this way, ESOTRAC will foster equality between urban and rural populations.
Economically, the costs of the novel endoscope will be comparable to currently existing systems, which can be amortized after ~ 1300 examinations. Most importantly, the implementation of the endoscope will reduce healthcare costs by cutting the 5-year average treatment costs of late stage EC of €130,000 down to around €12,000 upon early detection of disease. In turn, this means that for every 1% of the world population that can be shifted from late to early detection, i.e. ~ 4,500 patients, the healthcare savings are €541 million.
The consortium developed several exploitation strategies with the ESOTRAC market experts to allow for a quick introduction of the hybrid endoscope to the market. In conclusion, ESOTRAC will save costs, boost innovation in the European community, and – most importantly – save lives!
Schematic representation of the ESOTRAC Hybrid Endoscope