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Innovative Dermatology Healthcare based on Label-Free Spectral Optoacoustic Mesoscopy

Periodic Reporting for period 2 - INNODERM (Innovative Dermatology Healthcare based on Label-Free Spectral Optoacoustic Mesoscopy )

Reporting period: 2017-09-01 to 2019-02-28

Multispectral Optoacoustic Tomography (MSOT) is an imaging technology that generates high-resolution optical images in scattering media and as such dramatically improves upon conventional bio-optic barriers by enabling (1) three-dimensional high-resolution optical imaging deep inside tissues (several millimeters to centimeters), (2) high-scalability, ranging from optical-resolution microscopy to acoustic-resolution optical mesoscopy and macroscopy and (3) novel label-free anatomical, physiological and molecular contrast at the tissue and single-cell-level, based on spectrally-resolved optical absorption. Depending on the imaging depth and spatial resolution, MSOT allows for various regimens of imaging: microscopy, mesoscopy and macroscopy. At the mesoscopic level, Raster-scan optoacoustic mesoscopy (RSOM) has demonstrated imaging capacity at 1-5mm depths.
The goal of INNODERM is to develop a handheld, portable, scalable free RSOM prototype for point-of-care applications in dermatology. Compared to competing optical methods such as confocal microscopy or optical coherence tomography (OCT), RSOM images larger fields of view, images deeper and resolves new contrast.
During the first INNODERM reporting period, Raster-scan optoacoustic mesoscopy (RSOM), the main focus of INNODERM, has already shown unprecedented capacity to image skin and vasculature morphology and to quantify inflammation burden as exemplified in psoriasis conditions. While the first period of INNODERM was mainly dedicated to technical advancements and lab evaluation of RSOM, the second period was tailored towards testing of the device in other, equally urgent, dermatological settings and to optimize/adapt it for the general clinical use. Nevertheless, insights gained from the performance testing of RSOM within clinical settings were incorporated into a constant feedback loop to further optimize the device with regard to the end-user’s and patient’s needs.

On the technical side significant progress has been made ❶ in the transducer field in terms of sensitivity, artefact reduction and miniaturization (Objective 1), leading to ❷ the design and production of a handheld encapsulated probe (Objective 2), which is essential for clinical translation as it reduces the assessment times needed to ensure an user- and application friendly experience. ❸ Moreover, extensive effort went to the improvement of the reconstruction algorithm computation speed profiting from parallel computing through Graphic Cards Units. Importantly, now the system allows imaging of several wavelengths in parallel, setting the foundation to image the concentration of important biomolecules such as melanin, oxy and desoxy hemoglobin. We explored wavelengths beyond the visible and near infrared range to determine the optimal settings for visualization of lipids and water. ❹ In line with the INNODERM Objectives 3 and 4, the consortium built an optoacoustic microscope compatible with optoacoustic mesoscopy and tested it based on the general design proposed in the previous reporting period. The next step of INNODERM is now to explore the performance of mesoscopy/microscopy hybrid RSOM prototype in clinical applications ➎Based on Objective 5, we have applied RSOM intensively within various dermatology settings including: allergy testing, ultraviolet treatments, precision selective photothermolysis, inflammation and skin cancer. Most importantly, we are now able to determine the penetration depth of melanoma with single cell resolution. With this new ability, we expect to outperform current gold standard (ultrasound) for preoperative melanoma depth estimation providing clinicians a long-awaited, reliable tool for better melanoma treatment which undoubtedly represents a huge benefit for the patients. In addition, we were able to demonstrate that RSOM can visualize the response to treatment in psoriatic patients at depth, precision and sensitivity not imaginable before. With psoriasis being a highly prevalent chronic disease with immense socioeconomic burden, we expect our work to have a strong positive impact on the healthcare system.
Using the INNODERM prototype, the first portable RSOM device, we are able to provide a fresh view on different major skin diseases based on of the definition and establishment of a novel, objective clinical severity index for psoriasis outperforming the standard methods for severity assessment.
The main results so far were technical in nature and associated with dissemination activities. The consortium made key decisions on the final single element transducer specification, improved the transducer design in order to fulfil project requirements, agreed on the original RSOM design and specification and set the focusing and GRIN lens specifications. Regarding dissemination, INNODERM published 11 papers and gave more than 31 presentations related to INNODERM. Most importantly, INNODERM results gained attention not only through scientific publications and press releases word wide, but also through social media via tweets and public communication to raise awareness within the general public. The project webpage (http://innoderm2020.eu/) has been updated on INNODERM progress continuously;
The progress made within the second reporting period aligns well with the overarching goal of INNODERM to (a) reduce costs and (b) increase effectiveness in the field of skin imaging and in the long run, for RSOM to become the state of the art technology both in dermatology clinics and rural areas. The use of anatomical, chemical and metabolic parameters will provide early, reliable and quantifiable indicators of skin health, leading to an objective assessment of skin conditions. This will be of special benefit for patients with skin diseases that are currently hard to manifest or distinguish, e.g. irritation vs. allergic reaction. As such, the socio-economic impact of INNODERM will be substantial since it can provide the first reliable set of parameters that facilitate proper diagnosis and consequently optimal treatment early on, which in turn will benefit the healthcare system as a whole. The current state of the project indicates that the promise of RSOM being “a central tool for dermatology” is certainly plausible and will be soon a reality.
INNODERM Project