Periodic Reporting for period 3 - WINTHER (Fast optoacoustic mesoscopy, using the skin as a window for therapeutic monitoring of local and systemic disease.)
Reporting period: 2022-01-01 to 2023-06-30
Raster-scan optoacoustic mesoscopy (RSOM), which was developed under the EU Horizon 2020 project INNODERM, enables novel label-free, high-resolution optical imaging of previously invisible pathophysiological features at skin depths of 1-5 mm. The method has already shown great potential in diagnostic dermatology, and through preliminary testing it has become apparent that it can also assess progression and therapy of conditions not only in skin, but also in cardiovascular diseases and diabetes. However, the latter requires improvements in the speed of RSOM, which is where WINTHER begins.
The aim of WINTHER is to design and validate the next generation of RSOM, capable of operating at speeds up to two orders of magnitude faster. Such improvements will allow the new system, fast-RSOM (F-RSOM), to serve as a precision tool for therapy monitoring of inflammatory skin diseases and drive a paradigm shift in therapeutic monitoring of cardio-metabolic diseases.
The aim of WINTHER is to design and validate the next generation of RSOM, capable of operating at speeds up to two orders of magnitude faster. Such improvements will allow the new system, fast-RSOM (F-RSOM), to serve as a precision tool for therapy monitoring of inflammatory skin diseases and drive a paradigm shift in therapeutic monitoring of cardio-metabolic diseases.
During Reporting Periods 1-3, both technical and scientific achievements have been made. Specifically, the:
(1) Design, manufacture and validation of a new class of single-element transducers. Partner Sonaxis has led the way in this task, developing and testing (with help from TUM and iThera) several new iterations of single-element transducers with the best-performing having been selected and integrated into the prototype (Objective 1);
(2) Design, characterization, and implementation of an optimal illumination scheme for improved illumination efficiency. Partners Sonaxis, TUM and iTHERA were involved in this effort, by simulating and testing several illumination schemes (Objective 2);
(3) Design, testing and finalization of the F-RSOM encapsulated handheld prototype and software (including quality control and the investigation of information processing systems and computational efficiency to bridge the gap between information generation and clinical outputs by partners Rayfos, iThera and TUM), ensuring that all design and operation protocols adhere to safety and regulatory standards (Objective 2);
(4) Development of algortihms and deep-learning pipelines by partner TUM for accurate feature extraction and identification of relevant biomarkers for treatment monitoring in diseases such as melonoma (He et al., 2022; Objective 3);
(5) Pre-clinical and clinical validation and testing in vivo of the F-RSOM for cardiometabolic and dermatologic disease therapy monitoring by partners HUNIMED and TUM (Objective 4);
Following these achievements, in the final reporting period and last 12 months of the project, the WINTHER consortium will continue to validate the F-RSOM prototype, with the aim to secure regulatory approval in Europe (CE marking) and the US (501(k)) in 2024. Following regulatory approval, the focus of the project will steer toward exploitation (gaining clinical acceptance), Objective 5, and further research on therapy monitoring of cardio-metabolic diseases through pilot clinical studies by partners TUM and HUNIMED (Objective 4).
(1) Design, manufacture and validation of a new class of single-element transducers. Partner Sonaxis has led the way in this task, developing and testing (with help from TUM and iThera) several new iterations of single-element transducers with the best-performing having been selected and integrated into the prototype (Objective 1);
(2) Design, characterization, and implementation of an optimal illumination scheme for improved illumination efficiency. Partners Sonaxis, TUM and iTHERA were involved in this effort, by simulating and testing several illumination schemes (Objective 2);
(3) Design, testing and finalization of the F-RSOM encapsulated handheld prototype and software (including quality control and the investigation of information processing systems and computational efficiency to bridge the gap between information generation and clinical outputs by partners Rayfos, iThera and TUM), ensuring that all design and operation protocols adhere to safety and regulatory standards (Objective 2);
(4) Development of algortihms and deep-learning pipelines by partner TUM for accurate feature extraction and identification of relevant biomarkers for treatment monitoring in diseases such as melonoma (He et al., 2022; Objective 3);
(5) Pre-clinical and clinical validation and testing in vivo of the F-RSOM for cardiometabolic and dermatologic disease therapy monitoring by partners HUNIMED and TUM (Objective 4);
Following these achievements, in the final reporting period and last 12 months of the project, the WINTHER consortium will continue to validate the F-RSOM prototype, with the aim to secure regulatory approval in Europe (CE marking) and the US (501(k)) in 2024. Following regulatory approval, the focus of the project will steer toward exploitation (gaining clinical acceptance), Objective 5, and further research on therapy monitoring of cardio-metabolic diseases through pilot clinical studies by partners TUM and HUNIMED (Objective 4).
The WINTHER F-RSOM prototype will improve the capabilities of the current RSOM device to include fast measurements for assessing and monitoring of skin inflammation and cardio-metabolic diseases. The far-reaching impact of WINTHER, then, is to provide a long-term comprehensive platform for monitoring and diagnosing disease and therapy progress in a portable, non-invasive, inexpensive, label-free, fast and safe way. The ambitions of the project are aligned with the documented unmet clinical need and international physician recommendations.
The major results of this reporting period were technical in nature, with (1) beyond state-of-the-art transducers being developed (Sonaxis, iThera, TUM), (2) the design of a novel new ergonomic, portable scanner for non-invasive imaging (iThera, TUM), and (3) construction of a new clinically-friendly software that will enable high-quality optoacoustic imaging (Rayfos, iThera, TUM).
In addition to going beyond current clinical designs on the market, we imagine the expected results of the F-RSOM technology is to improve on cost, effectiveness and availability of therapeutic monitoring for dermatological and cardiovascular diseases, as well as diabetes. As such, the socio-economic impact of WINTHER could be substantial, as it will provide the first reliable set of parameters that facilitate proper diagnosis, monitoring and optimal treatment early on, which will benefit the healthcare system as a whole. The current state of the project indicates that the promise of F-RSOM bringing “a new dimension to optoacoustic mesoscopy” is plausible and will be soon a reality.
The major results of this reporting period were technical in nature, with (1) beyond state-of-the-art transducers being developed (Sonaxis, iThera, TUM), (2) the design of a novel new ergonomic, portable scanner for non-invasive imaging (iThera, TUM), and (3) construction of a new clinically-friendly software that will enable high-quality optoacoustic imaging (Rayfos, iThera, TUM).
In addition to going beyond current clinical designs on the market, we imagine the expected results of the F-RSOM technology is to improve on cost, effectiveness and availability of therapeutic monitoring for dermatological and cardiovascular diseases, as well as diabetes. As such, the socio-economic impact of WINTHER could be substantial, as it will provide the first reliable set of parameters that facilitate proper diagnosis, monitoring and optimal treatment early on, which will benefit the healthcare system as a whole. The current state of the project indicates that the promise of F-RSOM bringing “a new dimension to optoacoustic mesoscopy” is plausible and will be soon a reality.