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Photonics for Healthcare: multiscAle cancer diagnosiS and Therapy

Periodic Reporting for period 1 - PHAST (Photonics for Healthcare: multiscAle cancer diagnosiS and Therapy)

Reporting period: 2020-09-01 to 2022-08-31

The aim of PHAST is to develop an innovative training programme in the field of biophotonics able to offer society a team of highly skilled multidisciplinary scientists through a personalized PhD career development plan covering the fields of cutting-edge diagnostics and therapy of cancer diseases. An early diagnosis and targeted treatment of cancer require the development of innovative diagnosis tools and non-invasive methods to monitor a therapy response. The four specific objectives are:
1 In-vitro diagnosis as point-of-care approach through optical spectroscopy in combination with innovative sampling techniques
2 Tissue diagnostics and functional monitoring through optical fibre-based biopsy and diffuse optical spectroscopy
3 Microscale cancer monitoring through multimodal optical imaging of tumour borders during surgery
4 Macroscale therapy effectiveness monitoring by diffuse optical spectroscopy, multifunctional optical fibre sensors, and autofluorescence and hyperspectral imaging
The main results regarding the specific objectives are the following:
OBJ1 Development and testing of optical in-vitro diagnosis of cancer
- Trial developments of SERS-substrates with literature review of the available biological protocols for the detection of genomic biomarkers in body liquids
- Development of spectral acquisition protocols for Raman spectroscopic analysis of body fluids and research on a standardized sampling approaches
- Measurement by IR, spontaneous Raman and Stimulated Raman Scattering on reference samples and first measurements by Raman on breast cancer tissues
OBJ2 Development and testing of tissue diagnostics and functional monitoring
- Design of the basic fiber Bragg grating sensor configuration for single point blood pressure
- Design and fabrication of the basic SCOT system for laboratory and preliminary in vivo testing
- Design and development of a new system for interstitial TD-DOS spectroscopy and test on liquid phantoms based on established protocols.
OBJ3 Optimization and acceleration of surgical cancer therapy at a microscopic scale through multimodal imaging
- Design of the first endoscope, which has been evaluated at the Medical University of Vienna
- Implementation of an ultrahigh-resolution multimodal optical imaging platform
OBJ4 Optimization and acceleration of cancer therapy at macroscopic scale
- Functional studies and dissolution tests of in-house manufactured bioresorbable phosphate glasses fibres and capillaries
- Design and fabrication of anthropomorphic tissue phantoms of prostate and surrounding organs
- Enrollment of 12 patients on monitoring and predicting the efficacy of neo-adjuvant chemotherapy
- Development of a preliminary version of automated system for real-time tissue identification of gastrointestinal surgical guidance
- Development of a multimodal hyperspectral and image sensor for lung application
Referring to the PHAST four intersectoral photonic technologies, advancement over the state of the art is the following:
Progress beyond the state of the art:
- Study and development of novel SERS-based optofluidic devices
- Study and development of Standard Operating Procedures (SOP) for point-of-care RS to detect cancer markers in body liquids
Expected results:
- Synthesis of innovative SERS nanostructures, labels and surface biofunctionalization as well as novel microfluidic devices
- Development of cheaper and less intrusive ways to diagnose cancer or assess how cancer responds to treatment

The following directions will be pursued:
Progress beyond the state of the art:
- Development of next-gen hybrid diffuse optical device for monitoring tissue function in response to challenges
- Development of speckle contrast optical tomography (SCOT) for measuring deep tissue (>1cm) microvascular blood flow
- Incorporation of DO information into multimodalities probes for theranostics interventions with real time classification of suspect lesions
- Monitoring cancer treatment, in particular PDT via alterations in tissue absorption, and neoadjuvant chemotherapy via changes in breast lesion composition and structure.
Expected results:
- Develop of a SCOT setup for larger head coverage and of the first ever high-density head cap for imaginig cerebral blood flow in the adult brain
- Provide workstation for both interstitial spectroscopy in fine-needle optical biopsy and non-contact intraoperative tissue analysis
- Develop a tomographic reconstruction model for diffuse fluorescence signals which would enable imaging and quantifying of the concentration of fluorescing drugs in tissue and organs
- Acquisition of longitudinal clinical data on neoadjuvant patients for the estimate of tissue composition and correlation with medical information
- Fully automated multimodal diffuse reflectance, fluorescence spectroscopy for gastrointestinal cancer application

Multifunctional Optical Fibre Sensors
Progress beyond the state of the art:
Two studies will be carried out involving the following activities:
- Study and development of novel distributed fibre-based pressure sensor for the aid in the diagnosis of angiogenesis in cancer (brain tumours) and monitoring
- Development of an optical probe able to combine several functionalities by including into the fibre materials which are traditionally not used in fibre optics

Expected results:
- An optical fiber pressure sensor for diagnosing vascular lesions and angiogenesis in cancers using modified Fiber Bragg Gratings. Development of blood vessel phantoms using 3D printing technology
- A thin filament sized bioresorbable probe with channels for light and drug delivery to use in photodynamic therapy, integrated with technologies for monitoring the therapy or healing through the same probe

Multimodal Imaging
Progress beyond the state of the art:
The following multimodal imaging approaches are being pursued:
- Multimodal imaging utilizing imaging approaches with similar image acquisition times by integrating various nonlinear techniques (SHG, TPEF, CARS, SRS etc.)
- Imaging techniques yielding a large field of view of morphological information (e.g. OCT) are combined with molecular specific approaches (e.g. Raman, CARS, TPEF) to link morphological information with a richness of molecular details
Expected results:
- Spectral tissue imaging for ex-vivo cancer diagnosis and survey
- Development and testing of a first endomicroscopic system for simultaneous multimodal nonlinear imaging (CARS, TPEF and SHG) and fs laser ablation to simultaneously diagnose and treat cancer during surgery
- Micro-optical imaging system for multimodal non-linear endospectroscopy
- Multimodal endo-microscopy for improved in-vivo colorectal cancer diagnosis
- Multimodal intraoperative handheld forward-imaging probe
- Time Resolved SPAD Micro-Camera Probe for Wide-Field FLIm in Microendoscopy

Potential impact of the PHAST research project
Contribute to:
- Advanced photonic technologies for in-vitro and in-vivo diagnostics and therapy monitoring of cancer
- Train a new generation of high skilled scientists able to undertake the great challenges of photonics for healthcare
- Construct a network of scientific collaborations suitable for further progress and exploitation beyond the project end
- Create a portfolio of new technologies apt for deployment through start-ups or technology transfer
Raman sampling chip for point of care Raman measurements to identify pathogens
Optical mammograph applied for neoadjuvant cancer therapy monitoring
Multimodal imaging of meningioma brain sample at 60µm depth