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
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.
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.
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.