Multi messenger Imaging of Cancer

Description du projet

Faire progresser les ultrasons pour le diagnostic du cancer

Les ultrasons sont une méthode d’imagerie qui utilise les ondes sonores pour visualiser les organes et les tissus de notre organisme. Malgré sa sécurité, des limitations techniques ont jusqu’à présent entravé son application généralisée en oncologie clinique. Le projet MIC, financé par l’UE, exploitera les récentes percées technologiques pour développer une méthode de microscopie à ultrasons en 3D. L’idée est d’utiliser des agents de contraste qui permettent de visualiser les réseaux vasculaires dans le cancer et de détecter les ganglions lymphatiques métastatiques. Les résultats contribueront à faire progresser la détection par ultrasons des changements métaboliques et structurels dans le cancer, en offrant un outil non invasif aux oncologues.

Objectif

Cancer remains the second leading cause of death worldwide (World Health Organization), involving various pathological processes across multiple biological scales . Ultrasound is increasingly used in clinical oncological practice for patient diagnosis, therapy guidance, and monitoring, however do not allow for imaging of the metabolic and vascular onset of cancer at the microscale . Here, I aim to develop multi-messenger ultrasound imaging for the early metabolic and vascular detection of cancer in a pre-clinical model and a pilot human head and neck oncology study. This interdisciplinary proposal will build on three recent breakthroughs in ultrasound and synthetic biology: (1) 4D ultrasound imaging at the millisecond timescale, (2) ultrasound super-resolution imaging at the microvascular scale and (3) biomolecular ultrasound imaging at the cellular scale.I will develop non-linear sound sheet imaging (NSSI) for the 3D imaging of ultrasound contrast agents regardless of their motion. Combined with localization algorithms, this method will enable 3D ultrasound microscopy (SSLM) of capillary networks perfused with clinically approved contrast agents. Using this vascular message we will characterize rat brain tumors in preclinical research. We will also evaluate the potential of the ultrasound microscopy technique to detect metastatic sentinel lymph nodes in a pilot human study. Furthermore, NSSI will be capable of imaging GVs that are small enough to extravasate the leaky vasculature of tumors. In this specific aim, I will rely on genetically engineered pH-sensing GVs developed in my host laboratory (NWO Start-up Grant STU.019.021 of the Dutch Research Council). Using this metabolic message we will detect hypoxia induced acidosis, an important biomarker of cancer. The non-invasive observation of structural and metabolic messages arising from tumors with sound, named multi-messenger ultrasound imaging of cancer (MIC), will significantly advance the potential of medica