CTC-VideoScope
Developing a method for real-time detection and isolation of circulating tumor cells from the bloodstream of cancer patients by means of image processing and pattern recognition
Funding agency: Romanian Department of Education and Research, Joint Applied Research Project, PN-II-PT-PCCA-2013-4-2289.
Project budget:
- Finantare de la bugetul de stat: 1,250,000 lei
- Finantare din alte surse (cofinantare proprie): 187,500 lei
Project number: 137/2014
Project coordinator: "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca
Partner institutions: Technical University of Cluj-Napoca and Datronix Computer S.R.L.
Summary
Cancer is a major public health problem both in Western countries and in Romania. In general, cancer related death is caused by the occurrence of metastasis. The metastatic process begins with the migration of malignant cells from the primary tumor, followed by penetration into the circulation and their spread in the body. Circulating tumor cells (CTCs), the 'leukemic phase' of solid tumors, are the most promising tumor marker of the moment. They correlate with overall survival and disease free survival, allowing early detection of metastatic process, monitoring of disease progression and of treatment response. In addition, being the equivalent of a "liquid biopsy", CTCs offer the promise of personalized therapy based on their biomolecular analysis. CTC identification is a difficult task and there is no ideal method of detection yet. Most current methods have a low sensitivity because they analyze only a small sample of circulating blood. Oncology practice requires a sensitive method, allowing continuous monitoring over extended periods of time and which can be repeated frequently.
The current project aims to develop an automatic method for continuous real-time detection and isolation of CTCs from the bloodstream of cancer patients, based on their distinctive morphological characteristics. The method is inspired by the automated video surveillance systems of the highway traffic. Thus, one can imagine a portable, battery powered device, for continuous CTC monitoring over long periods of time, in conditions of total comfort for the patient (even at home). In principle, blood is continuously aspirated from the patient through a two-way intravenous catheter, is passed through the analysis device and then is re-injected through the same catheter. Inside the machine, the blood is gently pumped in a laminar flow at a constant speed through a transparent chamber-slide mounted in a phase contrast microscope. It allows visualization of live, unstained blood cells. Microscopic images, shot with a camera attached to the microscope, are transmitted to the computer system. This, by means of image analysis and pattern recognition will identify the CTC in real time based on distinct morphology, acting a downstream switch that diverts for a moment the blood flow towards one container, where the cell is stored for later analysis. The remaining blood flow, without CTCs, is re-injected into the patient.
The main goal of this project is to offer a “proof of concept” of this new method of detection, while the development of the commercial variant of the device will be relegated to a future project. Specifically, we will develope an experimental model to test in vitro blood samples from healthy volunteers, artificially spiked with malignant cells from cell culture. We will use commercial cell lines of breast, colon and prostate cancer, but we will also run real samples from patients with the same type of cancer. The method will be validated by comparative testing of similar blood samples with other well established methods. In addition, the viability of isolated CTCs will be tested by in vitro cultivation and by application of molecular biology techniques for evidence of specific mutations by RT-PCR, sequencing, in situ hybridization or immunocytochemistry.