Breaking the scattering barrier in deep tissue optical imaging by ultra-adaptive Holoscopy and microendoscop (UlHoMi)

• Applicant: Professor Dr. Gereon Hüttmann
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561182387

Though impressive progress has been made in recent years, optical imaging in scattering media is still a scientific and technological challenge with important applications in many fields, and in particular in biomedicine, where the complex structure of biological tissues render them opaque to conventional imaging techniques. In this proposal, we detail two promising parallel paths that tackle two of the fundamental limitations of noninvasive and minimally-invasive optical microscopy: label-free volumetric imaging through severe volumetric scattering, and flexible microendoscopy with extremely small footprint for volumetric minimially-invasive imaging at depths beyond the absorption limit. Tackling these fundamental and general challenges is made possible by the joint complementary expertise of the Israeli applicant, a world leader in the emerging field of 'wavefront-shaping' for imaging in complex media, and the German applicant, who developed and perfected 'Holoscopy', a volumetric acquisition and image reconstruction technique with unmatched performance in terms of imaging speed, resolution, adaptability, with pioneering results in biomedical imaging. Specifically, to break the current limits in tackling volumetric scattering, we propose to investigate the combination of the very recently-developed technique of the Israeli applicant, which marks a record in computational correction of scattering but is limited to planar or layered targets, with Holoscopy, which allows fast volumetric imaging. Efficient volumetric scattering compensation for imaging low contrast volumetric targets, as required for biomedical imaging, will be realized by combining novel algorithmic frameworks and optimized imaging acquisition. In the second path of minimally-invasive deep-tissue imaging, we propose to combine the recently developed 'distal holography' technique of the Katz group with Holoscopy-enabled measurements, to extend the current state-of-the-art from imaging only planar and relatively static targets to volumetric dynamic targets, with additional novel algorithmic compensation of aberrations, and the development of a miniaturized distal-holography probe for improved microscopic resolution, increase the resolution and provide the required distal reference holographic wave. Our proposed project, once realized, will establish a basis for new possibilities for imaging in complex media, with potential applications well beyond biomedicine.

• DFG Programme: Research Grants
• International Connection: Israel
• Partner Organisation: The Israel Science Foundation
• Cooperation Partner: Professor Dr. Ori Katz