The DePIcT project:

The DePIcT concept.

The PIXSCAN-FLI is a spectral Photon Counting micro-Computed Tomography (PC-CT) for in vivo small animal imaging based on the hybrid pixel technology developed for particle physics experiments. It includes a dedicated data processing pipeline adapted to this new physics of acquisition. The superiority of PIXSCAN-FLI with respect to other methodologies based on micro-CT, particularly its sensitivity and reliability, have been illustrated through several significant achievements among which: i) high detectability at low contrast and low X ray doses, ii) high image quality in the context of in vivo imaging, iii) fast dynamic radiographic capabilities at unprecedented acquisition rates in X-ray imaging (69 images/s and more), iv) contrast agent identification and imaging quantification. Further work concerns the implementation of deep learning state-of-the-art algorithms into the data processing and 3D reconstruction pipeline of the PIXSCAN-FLI.

Through a collaborative research between IBDM and CPPM, we recently applied the PIXSCAN-FLI methodology for in vivo imaging studies in a clinically relevant mouse model of hepatocellular carcinoma (HCC), the Alb-R26^Met mice. We uncovered a remarkable heterogeneity in the dynamics for tumours at the initiation phases. Instead, the growth curve of evolving tumours exhibited a comparable exponential growth, with a constant doubling time. Furthermore, longitudinal PC-CT imaging in mice treated with a combination of MEK and BCL-XL inhibitors revealed a drastic tumour regression accompanied by a striking remodelling of macrophages in the tumour microenvironment. Collectively, these studies illustrated the capability of the PIXSCAN-FLI to perform unprecedented longitudinal studies to track spontaneous liver tumours over a timeframe period up to 3 months. Moreover, the striking remodelling of macrophages in the microenvironment of regressing tumours we reported emphasizes how imaging strategies conceived to follow distinct tissue structures - cell populations - can guide towards optimal therapeutic settings. Thus, the PIXSCAN-FLI is today a mature powerful system dedicated to small animal longitudinal imaging to detect cancer initiation and progression, and to monitor its evolution during treatment.

The first objective is to acquire scientific knowledge on the tumour microenvironment remodelling and to translate findings into combinatorial therapies. We will explore the effectiveness of an immuno-therapy approach designed to remodel the tumour microenvironment while targeting cancer cells with drugs. First, we will develop combinatorial PC-CT imaging acquisition and processing using different contrast agents for qualitative/quantitative evaluation and 3D reconstructions of tumours, their vascularization, and tumour microenvironment. Second, based on knowledge gathered through imaging and marker analyses, we will assess the effects of treatments combining agents acting on the immune checkpoint pathway with those targeting cancer cells. Effects will be qualitatively/quantitatively evaluated on tumour cells, tumour microenvironment, and tumour vessel network.