ESOHISTO proposes a radically new scientific concept to revolutionize disease research, diagnosis and treatment by real-time imaging of 3D organization of diseased cells, cell-cell and cell-matrix interactions, and their biochemical events in large living human tissue/organs. This transformative vision of 'in vivo histology and histochemistry' is not yet feasible for most human organs. However, GI mucosa, the shallow lining of GI tract where many GI cancer originates, is a unique tissue to implement the ambitious vision of ESOHISTO by developing disruptive endosocpic technologies to provide a long-awaited solution to the insufficient diagnosis and early detection of GI cancers. The landscape changing ability of ESOHISTO is attributed to its key invention of a volumetric-projection confocal laser endomicroscopy (VP-CLE) and a multimodal approach to complement VP-CLE with advanced imaging methods including optical coherence tomography (OCT) and optoacoustic mesoscopy (OPAM). The novel volumetric projection method allows VP-CLE to provide 3D cellular features and molecular profiles at high speed and without any mechanic parts in the distal endoscope. OCT and OPAM delivers 3D morphology and pathophysiology of GI mucosa with an imaging depth far exceeding microscopy. The combination of VP-CLE, OCT and OPAM in a miniaturized endoscope heralds a paradigm-shifting GI cancer diagnosis scheme by replacing insensitive white light endoscopy and biopsy with comprehensive 3D OCT/OPAM inspection to identify subtle lesions and following 'zoom-in' cellular/molecular vision through VP-CLE to complete in vivo diagnosis. With its prospect of unprecedented 'in vivo histology and histochemistry' for GI cancer diagnosis and early detection, ESOHISTO is able to leverage European investment and know-how and strengthen EU citizens' well-being and economic growth by leading the market position in future GI endoscopic imaging.

RSENSE aims at revolutionizing optical sensing with broad impacts on society, by changing the paradigm in portable sensing for early detection in healthcare and on-board automotive and environmental sensing. RSENSE is driven by advanced portable optoacoustics (PROPT), developed and offered for the first time as a revolutionary biomedical and automotive sensor collecting unprecedented high-impact information unavailable to other technologies. PROPT is enabled by unique advances in laser diode and optoacoustic detection technology that improve sensitivity and reduce cost. Implemented with spectral ability, RSENSE will provide a low-cost, portable sensor with so far unavailable features, suitable for a wide spectrum of applications with superior performance over the current state of the art. Today’s optical sensing, including spectroscopy or imaging, is compromised when used in scattering media due to photon diffusion. In contrast to established optical sensors, the novel PROPT technology is insensitive to photon scattering, can decompose depth with high resolution, can be miniaturized and is inexpensive in the production. Rich medical and environmental literature have showcased that these features can play a transformative role in early detection of cardio-metabolic diseases and are urgently needed in environmental applications. Moreover, accurate phenotypic measurements are of high importance for epidemiology and large scale genomic analyses. RSENSE brings together non-conventional collaboration partners to support a visionary new path to optical sensing in cross-fertilized fields and allows development of a diverse application portfolio by using a disruptive technology with high impact potential. Successful completion of RSENSE will cumulate in ground-breaking new detection abilities in automotive, environmental and medical applications. Supported by experienced partners in research and exploitation, RSENSE initiates an innovation ecosystem with European leadership.

Optoacoustic (photoacoustic) imaging dramatically improves upon conventional bio-optic barriers and enables three-dimensional, high-resolution optical imaging deep inside tissues (several mm to cm). Clinical optoacoustic macroscopy has been supported by two ERC Advanced Awards (2008, 2016; Prof. Ntziachristos). In parallel, under the ICT program INNODERM, we developed mesoscopic optoacoustic imaging for dermatology diagnostics. Termed raster-scan optoacoustic mesoscopy (RSOM), the method can image previously invisible ❶ pathophysiological/oxygenation and ❷ morphological features of the skin at depths of 1-5mm. RSOM has already shown clinical diagnostic value in dermatology and, fuelled by INNODERM, has been commercialised and globally placed by iThera Medical. WINTHER builds on this success. While INNODERM focused on diagnostic dermatology, it has become apparent that RSOM can also assess progression and therapy not only in skin but also in cardiovascular diseases and diabetes. However, to achieve this, RSOM should be able to assess endothelial function, ability that it is not yet available. WINTHER will build next-generation fast RSOM (F-RSOM), operating up to two orders of magnitude faster than state-of-the-art RSOM, enabling it to assess not only ❶,❷ above but also ❸ endothelial function. Using the skin as a window for disease assessment and aided by a modern computation framework, based on deterministic and artificial intelligence algorithms, F-RSOM aims to improve the clinical accuracy of RSOM and shift the paradigm in therapeutic monitoring of cardio-metabolic diseases and inflammatory skin conditions, strengthening Europe's leadership in photonics and in personalized medicine. The project is driven iThera Medical with a strong history of commercializing optoacoustics for clinical applications, by leading physicians (TUM, HUNIMED), and by RSOM, RSOM components and data analysis experts (TUM, iThera, Rayfos, Sonaxis).

EUPHORIA will pave the way to establish MSOT (Multispectral Optoacoustic Tomography) technology for the non-invasive assessment of intestinal inflammation in patients. EUPHORIA will enable commercialization of the technology by finalizing technical improvements that will increase diagnostic outcome beyond what has been shown in a first feasibility study, will improve usability, prepare CE marking for the new device and validate clinical results in a large clinical study. Inflammatory bowel disease (IBD) is a chronic condition, posing significant burden to patients and health care systems. Patients suffer from a relapsing course of intestinal inflammation, and to date, there is no satisfying non-invasive diagnostic modality for monitoring disease activity. In a recent clinical study conducted by University Hospital Erlangen, MSOT, a technology developed by iThera Medical (ITM), has proven to be superior in diagnostic performance to other procedures. Imasonic (IMA) and RayFos (RFO) are ideally positioned to drive the technical improvement steps: Imasonic, an expert in ultrasound transducer manufacturing, will develop an ultrasound detector with higher signal-to-noise ratio to enable better sensitivity and detection at depth. RayFos specializes on real-time sensing and image inversion, processing and rendering and has significant experience in optoacoustic tomography algorithms and implementation. iThera Medical will lead the incorporation into the device, CE marking and commercialization. The University Hospital Erlangen is an excellence center in IBD and will drive the clinical validation. Pintail has extensive project management, dissemination and commercialization expertise.

Diabetes has emerged as a global pandemic affecting more than 420 million people worldwide, a number expected to further rise in the next decades. The disease has very heterogeneous outcomes and accurate patient staging or prediction of subsets of individuals likely to develop disease and/or progress to disease complications are currently unmet clinical challenges in need of urgent attention. OPTOMICS aims to research methodology that can deliver a paradigm shift in type 2 diabetes healthcare, by integrating 1) molecular phenotyping, 2) a new generation of phenotypic measurements in humans, representative of diabetes onset and progression, allowed by novel portable and non-invasive optoacoustic technology and 3) cutting-edge computational approaches leveraging progress in Artificial Intelligence. This research will develop and validate a digital twin model that catalyses a step change in shortening the path to translation, enabling applications in the entire spectrum from target identification & prevention/prognosis to patient stratification for type 2 diabetes and its complications. In addition to the research and technology goals, OPTOMICS places special attention to the ethical needs and implications of the work performed and further aims at exemplary project management, human measurements, dissemination and communication activities and updating an adept exploitation plan for the digital twin developed.