Research On Application Of Indocyanine Green Fluorescence Image-guiding In Solid Tumor Resection

Cancer remains a worldwide health problem and surgical resection is the main therapy for solid tumors.Surgeons have used their hands and eyes to evaluate tumor margins and detect micrometastases for the past years.Near infrared fluorescence guided surgery(NIRFGS)is gaining wide-spread utility in clinics owing to the technique's ability to provide better distinction between cancerous and normal tissues compared to a surgeon's human senses of sight and touch.To date,NIRFGS has primarily focused on using indocyanine green(ICG)as the beacon to find tumor tissues.ICG is injected into the patients' body intravenously and accumulates in tumors because of the EPR effect.During surgery once the body cavity is open,ICG can be excited by a certain wavelength of light(785nm)and emit another certain wavelength(820nm)of light which is invisible to naked eyes.The emitting light is collected by device and showed on screen to help surgeons make decisions.Though hundreds of cases using NIRFGS have been reported abroad,its application in China is still limited.On one hand,there is few devices available in the market.On the other hand,a lot of scientific and clinical research needs to be done to improve this technology.In this report,we built and developed a near infrared fluorescence image guiding system based on a research prototype and conducted a series of experiments which are as follows:A solution model and an animal model were established to simulate patient's tumor and the sensitivity and operability of the device were tested.The results confirmed that the device is highly sensitive,safe and effective.This work shows this approach using an FDA-approved fluorophore and a novel imaging device that is compact and convenient.In the process of that experiment,we noticed that the images varied between mice treated with the same procedure(same tumor type,injection dose,and waiting time before surgery).Despite the increased use of NIRFGS in clinics,there remains a lack of standardization as to what doses of ICG and preoperative times after ICG administration are optimal in terms of both tumor-to-background ratios(TBRs)and patient-to-patient variances within these ratios which complicates developing standardized device operation parameters during NIRFGS.We presented a method,using tumor models,that can quantitatively determine the concentrations of ICG within target and off-target tissues in real-time.We utilized the fluorescence signal to calculate the concentration of ICG in the tissue,and managed to eliminate skin signal.This method can also be applied to other optical contrast agents and may provide a new design idea method for studying the metabolism of fluorescent agent in vivo.We then used this method to study the metabolism of ICG in animal models.The results revealed that while greater ICG administrations leads to an averaged increase in TBR,to decrease variabilities among subjects requires longer preoperative periods at these larger doses.On the other hand,smaller doses have lower TBRs,but also have lower variabilities compared to larger doses at typical preoperative periods.This gave us two enlightenments-first is to increase the detection sensitivity of the device to make it applied to low-dose ICG injection;And second is to explore the mechanism of patient-to-patient variances on TBR and try to optimize dosage regimen such as personalized treatments to achieve a stable TBR.In addition to these studies,we found that some lymph nodes also had high fluorescence signals in our animal experiments.A small animal model of lymph nodes enlargement was developed to explore the application of NIRFGS in lymph nodedissection.NIRFGS showed its potential and application value in detecting lymph node metastasis in our studies and the mechanisms are worthy of further study.