Optical endomicroscopy and the road to real-time, in vivo pathology: present and future

Charles S Carignan, Yukako Yagi

Epithelial cancers account for substantial mortality and are an important public health concern. With the need for earlier detection and treatment of these malignancies, the ability to accurately detect precancerous lesions has an increasingly important role in controlling cancer incidence and mortality. New optical technologies are capable of identifying early pathology in tissues or organs in which cancer is known to develop through stages of dysplasia, including the esophagus, colon, pancreas, liver, bladder, and cervix. These diagnostic imaging advances, together as a field known as optical endomicroscopy, are based on confocal microscopy, spectroscopy-based imaging, and optical coherence tomography (OCT), and function as "optical biopsies," enabling tissue pathology to be imaged in situ and in real time without the need to excise and process specimens as in conventional biopsy and histopathology. Optical biopsy techniques can acquire high-resolution, cross-sectional images of tissue structure on the micron scale through the use of endoscopes, catheters, laparoscopes, and needles. Since the inception of these technologies, dramatic technological advances in accuracy, speed, and functionality have been realized. The current paradigm of optical biopsy, or single-area, point-based images, is slowly shifting to more comprehensive microscopy of larger tracts of mucosa. With the development of Fourier-domain OCT, also known as optical frequency domain imaging or, more recently, volumetric laser endomicroscopy, comprehensive surveillance of the entire distal esophagus is now achievable at speeds that were not possible with conventional OCT technologies. Optical diagnostic technologies are emerging as clinically useful tools with the potential to set a new standard for real-time diagnosis. New imaging techniques enable visualization of high-resolution, cross-sectional images and offer the opportunity to guide biopsy, allowing maximal diagnostic yields and appropriate staging without the limitations and risks inherent with current random biopsy protocols. However, the ability of these techniques to achieve widespread adoption in clinical practice depends on future research designed to improve accuracy and allow real-time data transmission and storage, thereby linking pathology to the treating physician. These imaging advances are expected to eventually offer a see-and-treat paradigm, leading to improved patient care and potential cost reduction.