Hypoxia Imaging Endoscopy Equipped with Laser Light Source from Preclinical Live Animal Study to First-In-Human Subject Research

Abstract

A goal in next-generation endoscopy is to develop functional imaging techniques to open up new opportunities for cancer diagnosis. Although spatial and temporal information on hypoxia is crucial for understanding cancer physiology and expected to be useful for cancer diagnosis, existing techniques using fluorescent indicators have limitations due to low spatial resolution and invasive administration. To overcome these problems, we developed an imaging technology based on hemoglobin oxygen saturation in both the tumor and surrounding mucosa using a laser endoscope system, and conducted the first human subject research for patients with aero-digestive tract cancer. The oxygen saturation map overlapped the images of cancerous lesions and indicated highly heterogeneous features of oxygen supply in the tumor. The hypoxic region of the tumor surface was found in both early cancer and cancer precursors. This technology illustrates a novel aspect of cancer biology as a potential biomarker and can be widely utilized in cancer diagnosis.

The future of endoscopy: Advances in endoscopic image innovations

“…To overcome this, a technique employing a combination of wavelengths with an imaging system composed of two laser diodes and a color CCD sensor it is possible to produce an oxygen saturation map based on the difference in absorption of oxy-hemoglobin and deoxy-hemoglobin accounting for hematocrit. 64,65 A proof of concept study involving 40 cases (n = 40) with established malignancies of the pharynx, oesophagus and colon illustrated a significant difference in the oxygen saturation map between the neoplastic and non- neoplastic areas in the oesophagus and colon only. These preliminary findings of functional imaging may aid diagnosis, predict response to cancer therapies including the outcomes of clinical trials pending larger scale study.…”

Estimation of tissue optical parameters with hyperspectral imaging and spectral unmixing

“…The glass capillary tube with an inside diameter of 1.15 mm is used to mimic the blood vessels and the intralipid strongly scattered incident light to simulate the living tissue around blood vessel [19]. Deoxyhemoglobin solutions were created by adding to every 5 mg of Sodium Dithionite per 1 ml of blood to achieve a sample with oxygen saturation of 0% [11].…”

Optical imaging of hemoglobin oxygen saturation using a small number of spectral images for endoscopic application

“…In Ref. 17, we reported on a clinical study of StO 2 imaging using a laser illumination endoscope system. The results showed that StO 2 imaging could clearly distinguish neoplasia from non-neoplasia in the esophagus and colorectum.…”

“…2, we developed a prototype endoscope system for gastroenterological endoscopy that allowed us to obtain StO 2 distribution images of tissue. As with the other types of our prototype systems, 17,28 the light source of the system provided four bands of light: two blue narrow bands at 450 and 470 nm, a green broad band, and a red band [ Fig. 1(c)].…”

“…We previously developed an StO 2 imaging technique based on three wavelength ranges and applied it to a laser illumination endoscope system. 17 Here, to argue for the application of StO 2 imaging to clinical endoscopy, it is important to show that tissue StO 2 can be obtained by a small number of wavelengths equivalently to a spectroscopy-based technique using many wavelengths. In this work, the physical principle of our method based on tissue optics is explained.…”