DS0412 - Innovation médicale, nanotechnologies, médecine régénérative, thérapies et vaccins innovants

ALIVE: An innovative medical device to improve the diagnostic of liver nodules and liver diseases analysing endogenous fluorescence – ALIVE

Submission summary

Primary liver cancer, including hepatocellular carcinoma (CHC) is the sixth most common cancer in the world with rising incidence. Early and accurate diagnosis is essential for proper management of cancer and patient survival. Diagnostic criteria mainly rely on updated AASLD and EASL imaging guidelines using CT and MRI. However, this strategy faces 2 challenges. First, increased arterial uptake and delayed washout, which constitute the hallmarks of non-invasive criteria, can also be observed in benign primary tumors, such as Hepatocellular Adenomas. Second, the reported sensitivity and specificity of imaging techniques decreases in lesions smaller than 2cm. Hence, in equivocal cases with imaging, a percutaneous biopsy is proposed, hampered by two drawbacks: the sample bias as a biopsy specimen does not fully represent the entire lesion, and the potential risk of bleeding and of tumoral cells seeding associated with any percutaneous biopsy. Novel attempts have been made to improve the overall performances of liver tumor characterization, using optical imaging (Hain et al., 2015). Indeed, several studies have analysed the contribution of endogenous fluorophores such as NAD(P)H, flavins, or lipofuscins of the liver autofluorescence (Croce et al., 2004). During HCC development, metabolism is increasing as mirrored by glycolysis rise, leading to an accumulation of NAD(P)H/H+ (Sato et al., 2007). Moreover, inflammatory processes associated with HCC induce a recruitment of inflammatory cells (Kawata et al., 1992) which, through their highly metabolic features, may be rich in NAD(P)H/H+ and FADH2 (Breslin et al., 2004). However, to our knowledge, no instrument using autofluorescence has been adapted for the diagnosis of deep-full organ lesions.
An innovative and minimally invasive medical device, Probea®, uses autofluorescence to help diagnosis and biopsy guidance. A feasibility study conducted with the Imaging and Pathology departments at CHU Henri Mondor has shown very promising results, with figures of sensitivity and negative predictive value of 100%, positive predictive value of 87.5% and specificity of 67% for the distinction of benign from malignant liver lesions. The objective of the ALIVE study is to develop novel diagnostic algorithms based on autofluorescence allowing a better characterization of liver nodules and underlying liver diseases on both adequate mice models and fresh human liver surgical specimens. The purpose of this project is to obtain all prerequisites to begin an international multi-centre clinical study.
The study will be organized in 3 distinct tasks: The first 2 tasks ambition to develop and optimize protocols for autofluorescence imaging in rodent models of liver inflammation, steatosis, fibrosis and induced liver tumors. The last task will allow the evaluation of the previously developed algorithms and techniques in ex-vivo analysis of human tumoral and liver tissue samples. The success of this project should allow the development of a Probea® device suitable for an in vivo prospective study in Humans which will follow the ALIVE project.

Project coordination

Alain Luciani (INSERM - Institut mondor de recherche biomedicale, U955, Eq18)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


INSERM - U955 INSERM - Institut mondor de recherche biomedicale, U955, Eq18

Help of the ANR 221,764 euros
Beginning and duration of the scientific project: September 2015 - 24 Months

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