Vibrational speckle tomography microscopy for fast intra-operative cancer tissue histopathology

Histology is central to the diagnosis, staging, and treatment of cancers. It requires the removal of small regions of suspect tissues (biopsies) that are later sectioned and stained with haematoxylin and eosin (HE). However, histology suffers from major weaknesses: First the standard HE protocol cannot work in vivo and requires ex vivo biopsies. Second HE is labour intensive, time consuming and the final tissue sections inspection is possible only after 12 hours. A faster but less accurate protocol, known as extemporaneous histology, can be performed in 40 min and is used in an intra-operative context to guide surgeries. The SpeckleCARS project aims to develop for the first time fast label free tomography microscopy with vibrational sensitivity to provide images with tridimensional improvement as compared to extemporaneous histology and in near-perfect concordance with conventional stained HE histology. This pioneering approach overcomes all the previous challenges: Using a wide field reflection scheme and label free contrast rules out all the drawbacks due to tissue removal and external labelling. It provides instantaneous intraoperative 3D histological data, improving the accessibility and accuracy of tumour detection, diagnosis and treatment. Combining the latest advances in 3D tomography reconstruction algorithms, high power laser systems together with key innovations in random speckle illumination and hyperspectral vibrational imaging, the SpeckleCARS project will provide for the first time volumetric histology imaging in real time over large (mm) fields of view without the need of tissue removal. To demonstrate the power of the developed technologies both ex vivo human and in vivo mouse cancer assessments will be conducted in collaboration with pathologists. The SpeckleCARS approach is broadly applicable to all cancer types and to any tissue diagnostic requiring histological data, so the project breakthroughs will benefit many medical and biology applications.