Vulvar skin, distinct from other areas, undergoes changes due to aging, causing symptoms like dryness and itchiness. While much research focuses on facial or forearm skin, vulva skin properties are underexplored. This study uses an in-house developed fiber-based Diffuse Reflectance Spectroscopy (DRS) system to assess vulva skin changes in 100 women. This objective evaluation includes analyzing tissue chromophores—water, lipid, oxyhemoglobin, and deoxyhemoglobin providing insights into moisture content, lipid levels, oxygen saturation, and blood fraction. DRS, compared to invasive methods, achieved a 65% accuracy in estimating estrogen levels, suggesting its potential for objective diagnosis and monitoring of genitourinary skin conditions.

SURGICAL OPTOMICS is a new -omics science that combines the study of light-tissue interactions and unique properties of photons with the use of advanced ML and DL algorithms to precisely characterize organs involved in the surgical scene and extract quantifiable tissue features and functions during the surgical procedure.

Intraoperative optical technologies such as Near-Infrared Fluorescence imaging, multispectral or hyperspectral imaging enable an improved visualization of unapparent anatomical structures, the evaluation of metabolic activities and the enhanced visualization of tumor tissue, when compared to white light evaluation alone. Thanks to some groundbreaking innovations, optical imaging can well be a powerful theranostic tool that can help tackling the challenges of surgical oncology: to ensure a complete removal of tumor tissue and to reduce the risk of surgical complications.

An extensive intelligence and networking activity, including main opinion leaders in the field, has allowed identifying 4 major axes of development of optical imaging, including:

1) SOFTWARE: the integration of computer-assisted interpretation of the optically generated signal through dedicated software solution and Artificial Intelligence, machine and deep learning approaches, towards the building of an OPTOMICS paradigm, in analogy with other omics (genomics, proteomics, metabolomics, radiomics).

2) HARDWARE: the development of improved hardware solutions, with optimized sensitivity and improved ergonomics.

3) CHEMISTRY: the development of innovative probes, which recognize precisely biological targets or tumor cells and allow for image-guided removal of cancers by focused energy delivery or surgical ablation.

4) TECHNIQUES: improvement of state-of-the-art techniques (surgical or interventional) by the implementation of optical imaging AND development of innovative minimally invasive organ-sparing techniques specifically enabled by optical imaging and surgical robotics.

We have been investigating Optical Coherence Tomography (OCT) as a tool to measure the tympanic membrane and middle ear morphology and vibrational response. The hand-held OCT ostoscope system, based on a 1.3 µm swept laser, is integrated into an endoscopy cart. It has an ~ 8 mm diameter field of view, 38 µm lateral resolution, 35 µm axial resolution, A-line rate of 200 kHz, and subnanometer sensitivity to vibration within the tympanic membrane and middle ear. The system has been used in the clinic at USC Keck Medical Center to image over 100 patients and healthy volunteers. Total imaging time is ~2 minutes, which allows it to easily fit into the clinic workflow, while providing high-resolution images and vibrometric assessment of the tympanic membrane and middle ear. The functional and morphological features visible within these image sets that allow us to readily differentiate among pathologies, will be discussed.

Doppler holography, employing high-speed digital imaging and near-infrared light, maps blood flow in the eye's fundus. It can be exploited to estimate quantitatively the velocity and volume of blood flow by assessing the Doppler frequency broadening increase in retinal arteries with respect to local surrounding tissue. This technique enhances our ability to gauge hemodynamics within these arteries across the cardiac cycle, crucial for ocular disease diagnosis and management. Infrared radiation scatters and broadens within the retina's deeper layers, aiding the analysis of blood flow in superficial retinal vessels. Light interaction with blood scatterers is quantified to estimate flow velocity, using a model of forward scattering for momentum transfer. The root-mean-square velocity reflects the degree of Doppler broadening, allowing for a detailed assessment of retinal hemodynamics. This approach provides a valuable tool for analysing ocular vascular health.

Macroscale fluorescence lifetime (FLT) imaging is emerging as a promising tool to improve tumor margin delineation and enhance contrast between tumor and healthy tissue during fluorescence-guided surgery. We have been developing the tauCAM, a custom-built time-gated CMOS camera with a high quantum efficiency (QE) in NIR (46%) and a resolution of 128x128 pixels, specifically for this application. The images obtained from the tauCAM are overlaid on high-resolution color images acquired with a dedicated color camera. We demonstrate the capabilities of our camera by performing in vivo studies on subcutaneous mice tumor models administered with nanobody- and antibody-based NIR tumor-targeted fluorescent contrast agents. The results indicate that FLT imaging enhances the contrast between tumor and healthy tissue.

Porphysomes are liposome-like nanoparticles self-assembled from a single porphyrin-lipid building block, which enables their inherent multifunction of photothermal, photoacoustic, photodynamic, fluorescence, PET, MRI, and drug delivery. Since its discovery, we have demonstrated porphysome’s high tumor selectivity and multimodal theranostic utilities in diverse tumor models and animal species. We have completed GMP manufacturing, GLP safety studies and clinical trial protocols for its first-in-human use, aka ‘beyond lab’. We have also developed a suite of next generation porphysomes that greatly broadened its theranostic applications from light to sound to radiation. These allow us to pursue new directions of ‘beyond light’ and ‘beyond cancer’.

Advanced-stage ovarian cancer becomes extremely challenging to treat effectively using current surgical and chemotherapy methods due to factors such as peritoneal metastasis, incomplete resection, and drug resistance. While photoimmunotherapy is emerging as a promising option for unresectable metastases, its full potential often goes unrealized due to varying treatment outcomes. This research effort aims to enhance the reliability, safety, and effectiveness of photoimmunotherapy for peritoneal metastases by combining targeted nanotechnology, fluorescence-guided intervention, and a state-of-the-art medical laser system.

This conference presentation was prepared for SPIE Photonics Europe, 2024.

Cancers of the upper gastrointestinal tract remain a major contributor to overall cancer risk. This study showcases the potential of diffuse reflectance spectroscopy in tissue characterisation intraoperatively during stomach and oesophageal cancer surgery. The data is normalised, and significant features are selected to improve tissue discrimination accuracy. Using a sterilisable reflection fibre probe, we achieved remarkable sensitivities: 88.11% and 97.09% for the stomach, and 88.35% and 95.05% for the oesophagus. The noteworthy outcomes of this research study have the potential to revolutionise surgical decision-making and accuracy, pushing the boundaries of technological integration in clinical practice.

This conference presentation was prepared for SPIE Photonics Europe, 2024.

In radiation therapy patients are treated by high energy x-ray beams with complex setup and treatment plans. Because of the nature of the setup and delivery, it is not possible to know the dose delivered, rather the clinic relies upon complex simulations and careful pre-treatment human setup steps. But the ability to image the treatment delivery by capturing the Cherenkov emission allows the treatment team to see the actually daily delivery to each patient, for the first time. Cherenkov cameras are time-gated image-intensified CMOS cameras that capture the small bursts of Cherenkov emission that occur in each 4 microsecond pulse of the linear accelerator. The cameras have been designed to self trigger on the scattered radiation, and the image intensifier only activates during the pulses, thereby suppressing ambient room lights significantly. The use of filtering and lens choice also maximize the sensitivity to achieve single-photon level imaging of Cherenkov emissions, with the room lights being present. The recent optimizations to the cameras and their use cases will be reviewed to illustrate the technical improvements and the value of this imaging to the clinical team.

Liver transplantation is a life-saving procedure for patients with end-stage liver diseases. However, the unbalance between number of transplanted patients and patients on waiting list is still an issue. The introduction of perfusion machines and the use of marginal organs tend to reduce this unbalance. However, all marginal organs cannot be transplanted as they suffer more frequently from post-transplant complications. Today there is no efficient method to assess the viability of the organ and therefore to select the marginal organs suitable transplantation. Tissue autofluorescence is an optical method which enables to detect metabolic activity and offer insights about liver viability. Our preliminary results with fluorescence measurements show that we can measure the relative concentration of different mitochondria biomarkers such as flavin, NADH and PpIX under different ischemia-reperfusion conditions on porcine model.

This conference presentation was prepared for SPIE Photonics Europe, 2024.

Hyperspectral imaging is a method that uses UV-NIR light to capture the physiological and morphological properties of biological tissues. A promising use case of HSI is the study and diagnosis of various types of tumors by extracting tissue parameters. This study examines various tissue indices as an alternative to tissue parameters extracted using the inverse adding-doubling (IAD) algorithm. Tissue indices were compared to tissue parameters extracted using IAD from simulated spectra, mice models, and healthy human forearms. Preliminary results indicate a positive linear correlation between melanin concentration and melanin indices, as well as total hemoglobin and hemoglobin indices. Tissue indices are promising for real-time tissue property extraction from hyperspectral images. They can potentially be used as a fast and accurate tool to aid in the diagnosis of tumors.

This conference presentation was prepared for SPIE Photonics Europe, 2024.

The high reoperation rate after breast-conserving surgery (in average 19% in the UK) is associated with the lack of efficient and easy to apply intraoperative methods for detection the tumour residue (“positive margin”) of the excised sample. In-situ tests, based on diffuse reflectance and intrinsic fluorescence spectroscopy could potentially palliate this problem by interrogating tissues at a depth of up to several millimetres. We evaluated three machine learning algorithms applied to a dataset of diffuse reflectance and fluorescence spectra consisting of 181 frozen breast samples, collected from 138 patients. The diagnostic accuracy depended on the applied algorithm and the AUCs ranged from 0.71 to 0.81 (maximal sensitivity 86.16%, specificity 58.97%) and is comparable with existent intraoperational modalities, such as, for example, MarginProbe. Further research is needed to find an optimal combination of spectral features and diagnostic algorithm.

We present a fully integrated, clinical-compatible SRS imaging device giving access to the complete Raman spectrum during tumor surgeries. Leveraging the advantages of a compact and robust fiber laser, we have integrated the entire microscopy system into a clinical cart, facilitating deployment in diverse clinical environments. The laser provides rapid tunability within milliseconds across a broad spectral range of 700 to 3300 cm^-1, covering biomedically relevant resonances in the fingerprint region. For detailed examination of larger tissue samples, we have designed a high-speed, low-resolution imaging mode to quickly identify cancerous hot-spots, followed by a high-resolution imaging mode.