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Functional optical coherence tomography

Final Report Summary - FUN OCT (Functional optical coherence tomography)

Final publishable summary report

Recent advances in medical procedures provide promising potential for effective treatment of numerous life-threatening diseases and impairing diseases affecting the aging population. Full exploitation of this potential, however, is inherently linked to performing early and specific diagnosis. In areas such as cancer screening and ophthalmology, current clinical practice calls for the development of techniques to diagnose disease in its early stages, when treatment is most effective and significant irreversible damage can either be prevented or postponed. Cross-sectional in vivo imaging provides a valuable clinical tool for the diagnosis, staging, and management of diseases. Emerging imaging methods are increasingly providing information on the physiology and molecular characteristics of lesions. Hence, the objective is to derive a multi-parametric biologic phenotype for diseases, e.g. tumours, based on imaging technology enabling precise guiding of treatment on an individual basis.

Non-invasive imaging is of fundamental and increasing importance in the daily disease management. Although physical examination and laboratory tests remain key methods for treatment planning and disease management, imaging increasingly represents a key objective metric in the diagnosis, and it is generally used multiple times during the course of a disease and also for monitoring of treatment efficacy. Imaging processes in biological tissue, i.e. functional information, is also increasingly applied in drug development processes and, thus, aid in developing new therapies.

Novel functional imaging platform
Optical coherence tomography (OCT) is an emerging non-invasive, optical diagnostic imaging modality that enables in vivo cross-sectional tomographic, 3-D visualization of internal microstructure and functional information in biological systems. OCT achieves axial image resolution of 1 to 5 micrometers with penetration depth of a few millimetres. Recent developments in light sources and systems have enabled OCT to perform non-invasive optical biopsy with performance approaching the level of that achieved with histopathology. Because OCT penetration is limited to a few mm into scattering tissue it is of importance to devise suitable delivery probes, e.g. endoscopes, to reach inner body parts. In this way, limited penetration is not hindering the unique ability of OCT for detection of pathologies arising in the vicinity of surfaces, i.e. minute epithelial pathological changes.

Functional OCT provides depth resolved physiologic, metabolic and molecular information from the tissue being imaged through polarisation sensitive OCT (PS OCT), Doppler OCT (DOCT), spectroscopic OCT (SOCT) and optophysiology. However, there is a strong need for increasing imaging speed, improving system technology and advancing delivery systems to successfully bring these potential imaging modalities into clinics. Optical coherence microscopy (OCM) combines OCT with a system of high numerical aperture in order to obtain transverse resolutions comparable to confocal microscopy but with increased depth of penetration.

Multiphoton tomography (MT) has become a well established optical imaging technique since its first exploitation more than a decade ago. MT is based on the detection of multiphoton excited fluorescence emitted by endogenous or exogenous fluorescent compounds. It allows thin optical sectioning from tissues at resolution surpassing that of OCT, but at less penetration depth. One key aspect of this proposal is the combination of OCT/OCM and MT for pre-clinical and clinical application expected to provide unprecedented capabilities in early cancer diagnostics.

The proposed novel medical imaging platform comprises high-speed, high-resolution, depthresolved, functional OCT and the integration of OCT/OCM with MT, hence, providing localized tissue function imaging. Albeit limited to mm-range penetration, this powerful platform may provide early diagnosis of numerous cancerous lesions and other diseases, such as retinal diseases, originating from minute pathological epithelial changes at the cellular level. It should be emphasised that the novel imaging technique complements existing technology to the benefit of patients through improved or even new diagnostics.

Aim, objectives and main targets

The over-all aim of FUN OCT is to expand the non-invasive optical biopsy capability of optical coherence tomography (OCT) and combination of OCT with multiphoton tomography (MT) to develop novel functional capabilities hereby enabling ‘morphofunctional’ performance, i.e. the fusion of anatomic and functional imaging at the cellular resolution level. These methodologies will enable unprecedented non-invasive detection of depth resolved physiological, metabolic as well as molecular specific tissue information, i.e. forming a novel, powerful medical imaging platform. The hypothesis is that the combination of cellular resolution, real time imaging of morphology and depth resolved tissue function could enable a major step forward in early cancer diagnosis and in the early detection of retinal pathologies that are worldwide leading causes of blindness.

The main objective of FUN OCT is to expand state-of-the-art OCT medical imaging capabilities to include depth resolved functional information, i.e. forming a novel, powerful medical imaging platform, and to demonstrate its general feasibility in selected clinical applications that can contribute to the enhancement of quality of life and living conditions of the European aging population. The creation of this medical imaging platform is realised through the development of optical ultra-broad bandwidth and ultrahigh speed tuneable light sources, optical, electronic, hard/soft-ware designs for functional OCT, delivery systems for the envisaged medical applications, and contrast agents to further enhance OCT tomogram contrast. These developments enable unique, three-dimensional, real time in situ functional imaging providing unprecedented depth resolved functional tissue information that is essential to significantly improve early cancer diagnosis as well as detection of retinal pathologies such as age-related macular degeneration (AMD) and glaucoma that are worldwide leading causes for blindness.

The outcome contributes directly to improving and to maintaining the quality of life and living conditions of the European aging population through early diagnosis of cancer and of retinal pathologies as well as more efficient therapy monitoring. Moreover, the new imaging modality may in the long term act as a screening device to investigate the prevalence of cancer as a function of geographic (regional) or gender related parameters. Finally, the diagnosis of other age-related diseases in a variety of medical fields, such as cardiology, neurology, gynaecology, and gastroenterology, may also benefit from this novel diagnostic platform provided by FUN OCT.

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