PROSCOPE is a diverse international consortium which is developing a new optical guided colonoscopy for the earlier detection and better treatment of colorectal cancer.
Colorectal cancer (CRC) is the second most common cause of cancer death in Europe, yet survival rates rise dramatically when caught early. A contributing factor is that current colonoscopy, i.e., white light video or optical narrow band imaging, is inadequate for in-vivo detection and characterisation of the various types of (pre-)cancerous lesions found in the colon.
Point-of-care, real-time polyp diagnosis and image guided intervention has the potential to have a major impact by enabling early onset of treatment; thus reduced recurrence rate, by improving interval screening, and by reducing pathology costs incurred during colonoscopy.
A complete, reliable optical diagnosis is sensitive to morphological and biochemical changes. Unfortunately, no single optical method provides both. PROSCOPE seeks to provide a unique combination of label-free, non-ionizing, proven optical imaging modalities that provides higher sensitivity and specificity compared to current colonoscopy. This will enable a step-change in point-of-care management of CRC.
PROSCOPE is working to develop and integrate recent advances in optical imaging and optical probe technology into one platform. The concept will be validated in clinical settings using existing endoscopes providing minimally invasive optical imaging that fits into current clinical procedures.
Leading medical device and clinician expertise is involved at every stage of the development and validation. PROSCOPE is driven by unmet clinical needs in the field of gastroenterological diagnosis with a clear business case: Combination of optical imaging techniques offers the potential to vastly improve early diagnosis of CRC achieving specificity and sensitivity above 90%, reducing the number of excisional biopsies by 50%, and improving interval screening planning, thereby reducing healthcare costs drastically and benefitting patients.
For further information on PROSCOPE’s work please contact the coordinator.
During the course of the project’s work updates on research will be published here. All associated patents can be seen here.
Publications
Title: Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks
Summary: By using neuronal networks on high definition optical coherence tomography data, pituitary adenoma can be discriminated by pituitary gland tissue in a detailed way.
Citation: A. Micko, F. Placzek, R. Fonollà, M. Winklehner, R. Sentosa, A. Krause, G. Vila, R. Höftberger, M. Andreana, W. Drexler, R. A. Leitgeb, A. Unterhuber, and S. Wolfsberger, "Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks," Frontiers in Endocrinology 12, 1345 (2021).
Available here.
Title: Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging
Summary: Our multimodal imaging approach allows to discriminate adenomas in the pituitary gland, by combining optical coherence tomography, multi- photon microscopy, and Raman spectroscopy.
Citation: G. Giardina et al., "Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging." Cancers 2021, 13, 3234.
Available here.
Title: Manufacturing and assembly of an all-glass OCT microendoscope
Summary: We present a forward-looking, fiber-scanning endomicroscope designed for optical coherence tomography (OCT) and OCT-Angiography (OCT-A) imaging through the working channel of commercial gastrointestinal endoscopes and cystoscopes. 3.4 mm in outer diameter and 11.9 mm in length, the probe is capable of high-resolution volumetric imaging with a field-of-view of up to 2.6 mm and an imaging depth of up to 1.5 mm at a lateral resolution of 19 µm. A high-precision lens mount fabricated in fused silica using selective laser-induced etching (SLE) allows the tailoring of the optical performance for different imaging requirements. A glass structure fabricated by the same method encapsulates the optical and mechanical components, providing ease of assembly and alignment accuracy. The concept can be adapted to high resolution OCT/-A imaging of various organs, particularly in the gastrointestinal tract and bladder.
Citation: Yanis Taege et al 2021 J. Micromech. Microeng. 31 125005
Avaiable here.
Title: Design parameters for Airy beams in light-sheet microscopy
Summary: We derive analytical expressions for the length, thickness, and curvature of an Airy light sheet in terms of basic parameters of the cubic phase and the paraxially defined focusing optics that form the beam. The length and thickness are defined analogously to the Rayleigh range and beam waist of a Gaussian beam, hence providing a direct and quantitative comparison between the two beam types. The analytical results are confirmed via numerical Fresnel propagation simulations and discussed within the context of light-sheet microscopy, providing a comprehensive guide for the design of the illumination unit.
Citation: Yanis Taege, Anja Lykke Borre, Madhu Veettikazhy, Sophia Laura Schulz, Dominik Marti, Peter Eskil Andersen, Bernhard Messerschmidt, and Çağlar Ataman, "Design parameters for Airy beams in light-sheet microscopy," Appl. Opt. 61, 5315-5319 (2022)
Available here.
Title: Meshless Monte Carlo radiation transfer method for curved geometries using signed distance functions
Summary: Monte Carlo radiation transfer (MCRT) is the gold standard for modeling light transport in turbid media. Typical MCRT models use voxels or meshes to approximate experimental geometry. A voxel-based geometry does not allow for the precise modeling of smooth curved surfaces, such as may be found in biological systems or food and drink packaging. Mesh-based geometry allows arbitrary complex shapes with smooth curved surfaces to be modeled. However, mesh-based models also suffer from issues such as the computational cost of generating meshes and inaccuracies in how meshes handle reflections and refractions.
We present our algorithm, which we term signedMCRT (sMCRT), a geometry-based method that uses signed distance functions (SDF) to represent the geometry of the model. SDFs are capable of modeling smooth curved surfaces precisely while also modeling complex geometries. We show that using SDFs to represent the problem’s geometry is more precise than voxel and mesh-based methods.
Citation: Lewis McMillan, Graham D. Bruce, and Kishan Dholakia "Meshless Monte Carlo radiation transfer method for curved geometries using signed distance functions," Journal of Biomedical Optics 27(8), 083003 (4 August 2022)
Available here.
Title: Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams
Summary: Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000–10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.
Citation: Wijesinghe, P., Corsetti, S., Chow, D.J.X. et al. Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams. Light Sci Appl 11, 319 (2022). https://doi.org/10.1038/s41377-022-00975-6
Available here.
Title: Spatially offset optical coherence tomography: Leveraging multiple scattering for high-contrast imaging at depth in turbid media
Summary: The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth. Here, we investigate the role of multiple scattering in OCT image contrast and postulate that, in OCT, multiple scattering can enhance image contrast at depth. We introduce an original geometry that completely decouples the incident and collection fields by introducing a spatial offset between them, leading to preferential collection of multiply scattered light. A wave optics–based theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by more than 24 decibels. Notably, a ninefold enhancement in image contrast at depth is observed in scattering biological samples. This geometry enables a powerful capacity to dynamically tune for contrast at depth.
Citation: Gavrielle R. Untracht et al. ,Spatially offset optical coherence tomography: Leveraging multiple scattering for high-contrast imaging at depth in turbid media.Sci. Adv.9,eadh5435(2023)
Available here.
Title: Generation of biaxially accelerating static Airy light-sheets with 3D-printed freeform micro-optics
Summary: One-dimensional Airy beams allow the generation of thin light-sheets without scanning, simplifying the complex optical arrangements of light-sheet microscopes (LSMs) with an extended field of view (FOV). However, their uniaxial acceleration limits the maximum numerical aperture of the detection objective in order to keep both the active and inactive axes within the depth of field. This problem is particularly pronounced in miniaturized LSM implementations, such as those for endomicroscopy or multi-photon neural imaging in freely moving animals using head-mounted miniscopes. We propose a new method to generate a static Airy light-sheet with biaxial acceleration, based on a novel phase profile. This light-sheet has the geometry of a spherical shell whose radius of curvature can be designed to match the field curvature of the micro-objective. We present an analytical model for the analysis of the light-sheet parameters and verify it by numerical simulations in the paraxial regime. We also discuss a micro-optical experimental implementation combining gradient-index optics with a 3D-nanoprinted, fully refractive phase plate. The results confirm that we are able to match detection curvatures with radii in the range of 1.5 to 2 mm.
Citation: Yanis Taege, Tim Samuel Winter, Sophia Laura Schulz, Bernhard Messerschmidt, Çağlar Ataman, "Generation of biaxially accelerating static Airy light-sheets with 3D-printed freeform micro-optics," Adv. Photon. Nexus 2(5) 056005 (1 August 2023)
Available here.
Title: Field curvature reduction in miniaturized high numerical aperture and large field-of-view objective lenses with sub 1 µm lateral resolution
Summary: In this paper the development of a miniaturized endoscopic objective lens for various biophotonics applications is presented. While limiting the mechanical dimensions to 2.2 mm diameter and 13 mm total length, a numerical aperture of 0.7 in water and a field-of-view (FOV) diameter of 282 µm are achieved. To enable multimodal usage a wavelength range of 488 nm to 632 nm was considered. The performed broad design study aimed for field curvature reduction when maintaining the sub 1 µm resolution over a large FOV. Moreover, the usage of GRadient-INdex (GRIN) lenses was investigated. The resolution, field curvature improvement and chromatic performance of the novel device were validated by means of a confocal laser-scanning-microscope.
Citation: Sophia Laura Stark, Herbert Gross, Katharina Reglinski, Bernhard Messerschmidt, and Christian Eggeling, "Field curvature reduction in miniaturized high numerical aperture and large field-of-view objective lenses with sub 1 µm lateral resolution," Biomed. Opt. Express 14, 6190-6205 (2023)
Available here.