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Precision Multi-Spectral Optoacoustic Tomography for Discovery Diagnosis and Intervention

Periodic Reporting for period 4 - PREMSOT (Precision Multi-Spectral Optoacoustic Tomography for Discovery Diagnosis and Intervention)

Okres sprawozdawczy: 2021-07-01 do 2022-12-31

In PREMSOT the clinical translation of multispectral optoacoustic tomography (MSOT) was catapulted to the next level, significantly advancing the accuracy of medical diagnosis and therapy monitoring for a variety of diseases. Precision medicine redefines diagnostic and interventional challenges and requires accurate, quantitative observation of pathophysiological tissue parameters and treatment effects.

As we advance personalized medicine it becomes crucial to design tools for quantitative tissue readings that solve limitations of current technologies. MSOT measures light (photon) absorption, without being sensitive to photon scatter, as in conventional optical imaging, due to utilizing sound for detection (instead of light). Optical absorption relates to unique morphological and functional parameters, imaged by MSOT in a label-free mode (no contrast agents). Therefore, MSOT redefines optical imaging by making it cross-sectional, depth resolving and high-resolution within depths of millimetres to centimetres and offering unique imaging features not available to other radiology methods. Optoacoustic imaging is probably the most qualified method for non-invasive imaging oxygenated and deoxygenated haemoglobin (tissue oxygenation), haemoglobin concentration (blood volume / ischemia) and microvasculature in a portable format.

In PREMSOT a next-generation label-free imaging platform was developed that brings advances over existing MSOT technology by theoretical and hardware developments that solve critical current limitations in MSOT sensitivity, accuracy and quantitative capacity, which were then validated, relating the novel imaging features offered to quantitative pathophysiological parameters of tissue/disease. Furthermore, MSOT was applied to clinical discovery and care addressing unmet clinical needs requiring MSOT, particularly to vascular medicine but also to other diagnostic and theranostic settings.
Along with our central aim within PREMSOT we developed a handheld label-free video-rate multi-spectral optoacoustic system delivering unprecedented imaging features, with emphasis on imaging hemoglobin saturation / tissue oxygenation and vasculature. We designed an improved detector with enhanced imaging capabilities deep in tissue based on a detailed analysis of the system. The new detector was operated with an MSOT prototype and a flexible software solution in clinical studies on human breast cancer. We introduced a deep-learning-based method for electrical noise removal where we made subtle optoacoustic contrast within a breast tumor visible behind the system noise and visualizing for the first time specific features of different breast tumors. This ability improves the diagnostic value of clinical MSOT.

In parallel we developed theory and algorithms that improve the sensitivity and the quantification accuracy of imaging tissue oxygenation, hypoxia, blood (haemoglobin) volume, vessel and micro-vessel morphology and flow, leading to label-free tissue readings appropriate for precision medicine. We improved the quantification of tissue properties from optoacoustic data by implementing advanced regularization schemes, engineering novel biomarkers, and designing novel data acquisition schemes. We exploited the advantages of the perfectly coregistered optoacoustic and ultrasound images of our system, achieving an improved molecular contrast in depth, thereby increasing the accessibility of medical information.

We have demonstrated in various case studies a broad applicability of MSOT and that it can be used as a novel modality for the assessment of vascular, muscular and metabolic disorders characterized by disturbed blood flow, such as peripheral arterial disease (PAD), deep vein thrombosis (DVT), heart failure and diabetes mellitus. We were able to image muscle hemodynamics and oxygenation changes under conditions of disturbed blood flow. Our results open up new possibilities to investigate muscle oxygenation and metabolism in health and disease using MSOT and attempt to shift the paradigm from only imaging the cause of the disease, towards imaging the target organ (muscle) non-invasively, label-free and in real-time.

Results of PREMSOT were published in more than 60 scientific outputs and were presented at more than 70 national and international conferences addressing the scientific community, industry, medical end-users, and healthcare stakeholders. The results fed directly into successful applications for additional funding to develop new optoacoustic devices or to advance commercialized technologies.
PREMSOT has established state of the art multispectral optoacoustic tomography systems. The achievements are a breakthrough in optoacoustic imaging applications pushing the status-quo to a next and higher level, bringing it much closer to a foreseeable translation into general clinical practice. Our advancements of hardware, software and AI tools and the numerous case studies for new applications of MSOT have brought the technology much closer to regular clinical use where first of all patients will benefit the most. By mediating the early detection of disease such as cancer or enabling personalized therapy MSOT will reduce healthcare costs in the EU dramatically by shifting expensive treatment of lately diagnosed disease to treatment in an early stage which mostly comes at a much lower cost. We opened up the field of metabolic investigations for a wide variety of diseases or associated traits of health. It will be possible based on our pioneering work that MSOT becomes the most convenient – in terms of patient comfort and safety – and affordable technology, e.g. compared to MRI screening, for a plethora of metabolic investigations to support measures in the fight against obesity or diabetes such as exercise and diet or even for sports medicine. These results were not foreseen when the project started and showcase that the versatility of MSOT and our other optoacoustic imaging and sensing devices goes far beyond what was known or anticipated a few years ago. It can bring novel insights on patient’s health traits and response for personalized therapy in Diabetes, cardiovascular and cardio-metabolic diseases or cancer. Our advancements of data acquisition and reconstruction also with the use of AI tools such as machine learning are a prerequisite for enabling radiologists to successfully apply MSOT in regular medical investigations. Our research directly feeds into the advancement of new hardware and software solutions for MSOT.

In addition to advancing MSOT, we developed mid-infrared optoacoustic microscopy (MiROM) for label-free, bond-selective, live-cell metabolic imaging. This modality is among the best in the world to study tissue metabolism in live-cell imaging with outstanding resolution. We further developed a range of synthetic and bio-engineered agents suitable for combined optoacoustic imaging and therapy (theranostics). Finally, we want to highlight our advancements on technology and quantification for raster-scan optoacoustic mesoscopy (RSOM). This device operating on a smaller scale compared to MSOT provides highest resolution and contrast throughout the skin and can be applied to many different dermatological diseases or systemic diseases such as diabetes where the skin serves as a window to the body where it often surpasses the recent gold standard assessment tools for these diseases.
Prototype of a Raster-Scan Optoacoustic Mesoscopy (RSOM) system