Non linear photonics: developments & applications in biomedical imaging

Abstract

Nonlinear polarization is explored in a biological and a technological contexts. Experimental set-ups are developed and built for interrogating nonlinear polarization in biological environment. Most notably, a Coherent Anti-Stokes Raman Scattering (CARS) and Second Harmonic Generation (SHG) microscopes are implemented in the Institute for Life Sciences (IfLS) at Southampton University. CARS and SHG are nonlinear effects based on different contrasts but both are label-free−and as a consequence truly in vivo; without perturbation of the biological mechanisms in opposition to fluorescence techniques (gold standard)− and enable fast imaging of living tissues, organisms and cells at 450 nm lateral spatial resolution. In collaboration with the mass-spectroscopy group at the General Hospital at Southampton and MedImmune, the capabilities of CARS & SHG are assessed for characterization of Pulmonary Alveoli Proteinosis (PAP) disease and drug impact on this phenotype and compared to its healthy version by tracking lipid droplets and collagen fibres. In an other collaboration with the clinical neuroanatomy and experimental neuropathology group at the University of Southampton, age related cerebrovascular and neurodegenerative diseases are linked to maternal obesity thanks to CARS thanks to its ability to track lipid droplets. In a second whole new project, multiplex CARS & SHG modalities are implemented and adapted to large area 4 mm2. Its methodology is developed. This last implementation allows microscopic and label-free characterization of large section of tissues which are compared to H&E (gold standard) valued by histological studies and proposed as a promising alternative. This ability leads to the development of a novel feature: texture analysis. The results obtained display novel insights and ability to characterize and localized healthy, pre-malignant and cancerous areas in tissues by a robust and unsupervised manner. Moreover, cancerous types could be further identified by this method. These results open up and bring the use of CARS & SHG for endoscopy/operative intervention for cancer/dysplasic localization at μm scale without prior labeling to an unprecedented level of specificity. To finish, a novel spectral CARS architecture is theoriticalized displaying unprecedented breadth and sensitivity; and enables the detection of many−usually too weak−biological Raman features.

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Identifiers

ORCID for Sumeet Mahajan: orcid.org/0000-0001-8923-6666

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