• CCD
• Cerenkov luminescence imaging
• In-vitro optical imaging
• Liver optical properties

This master thesis is dedicated to an in-vitro study with a Cerenkov luminescence imaging system, with the goal of planning and optimizing the clinical protocol for its application in margin determination during hepatic metastasectomy.
Surgery is the most used treatment of many solid and localized tumors. However, its effectiveness is given by a compromise between complete tumor resection and maximum sparing of the surrounding healthy tissues. Nowadays, the tumor size is determined pre-operatively with a PET/CT scan, and information on the tumor margins is either given by frozen-procedure, later confirmed by post-operative histopathology, or by the latter alone.
Cerenkov luminescence imaging (CLI) is a novel functional imaging technique based on the detection of optical Cerenkov photons emitted by positron emission tomography (PET) imaging agents. Recently, CLI has been proposed as an intraoperative adjunct to aid in real-time margin identification. If before surgery the patient has received an intravenous injection of a PET radiopharmaceutical (e.g. 18F-FDG of 68Ga-HCl) with high uptake in the tumor, the presence of a signal coming from the resected specimen indicates if margins
are negative (no signal) or if surgery needs to be refined (signal).
Several studies have already demonstrated the (pre-)clinical feasibility of CLI for intraoperative specimen analysis and a dedicated imaging device called LightPath has been developed by Lightpoint Medical Inc. To date, two research groups have evaluated the performance of this system, demonstrating the linearity of its response to various amounts of 68Ga and 18F, and a detection limit and resolution comparable with clinical requirements. However, these results are limited to a fixed depth in tissue and to a specific type of tissue.
This thesis focuses on the study of the sensitivity of the imaging system, with the goal of obtaining a set of lower and upper limits to the minimum detectable activity concentration for 68Ga and 18F as a function of depth in liver, to be compared with typical uptake values in liver metastases. To this aim, 68Ga-HCl and 18F-FDG, either diluted in distilled water inside petri dishes or uniformly distributed in agar-based solid phantoms, were placed at various depth in ex-vivo animal liver specimens. The optical attenuation of the liver tissue was studied. Finally, a method for source depth estimation was tested by using 550 nm short-pass filters to select only photons generated near the surface of the tissue.
This work provides some values to compare the detection limit obtained for different geometry and radionuclide, in air and at clinical relevant depth in tissue. The minimum detectable activity in the animal liver results comparable with the typical uptake in liver metastasis. This result suggests that intra-operative Cerenkov luminescence imaging in the liver is likely to be feasible.