Noninvasive Liver Function Assessment by Use of the Fluorescence of Indocyanine Green

According to the investigation of the Ministry of Health and Welfare in 2014, cancer is the most common cause of death in Taiwan, and hepatic cancer is the second leading cause of cancer-related death. Over 10 thousands of people die of hepatic diseases, so it is essential to raise the survival rate in treatments to hepatic cancer. Methods of treatment to hepatic cancer include hepatectomy, liver transplant, chemotherapy, radiotherapy, etc. Hepatectomy and liver transplant are the most feasible methods to eradicate hepatic cancer. However, it is impossible to conduct hepatectomy on every patient. If the postoperative liver cannot afford the metabolism of the whole body, it will lead to liver failure which is immortal. Therefore, the preoperative assessment of liver function is of importance. Currently, the standard assessment method is Indocyanine Green (ICG) clearance test, and ICG is a kind of dye which would be metabolized almost by the liver only. By measuring the retention rate of ICG in blood, doctors can evaluate liver functions in order to determine the feasibility of hepatectomy and the ratio of the liver to be resected. Generally, after 15-minute administration, the retention of ICG of healthy people will below 10%, but the retention of ICG of patients with severe hepatic diseases could be over 40%. To quantify ICG concentration, the traditional way is to draw blood after administration at 5, 10, 15 minutes and measure the ICG concentration in the blood samples by spectrophotometry. This method is invasive, discontinuous, and with human-caused errors, so it is more incorrect. Developing a fluorescence-based detector system excited by a single photon laser, we are able to detect the ICG fluorescence noninvasively, and then calculate the retention time of ICG in blood. The advantages of this approach are noninvasively and continuously monitoring the ICG retention rate with high contrast. In the first step, we acquired the THG images and the ICG two-photon fluorescence images at the same time so that the imaging plane of blood vessels could be fixed. We ensured that ICG would not diffuse out of vessels, so it is feasible to collect the ICG fluorescence by large area excitation. The result showed that, in the control group, the ICG fluorescence intensity after 15-minute administration is lower than 10% of the initial intensity; in the HCC group, the intensity after 15-minute administration is over 40% of the initial intensity, which is consistent with the traditional method. In the second step, we transfer the design to single-photon excitation scheme. We used a single-photon laser as the light source and removed the telescope and the scanner parts. The only signal we detected came from the ICG fluorescence. Moreover, the efficiency of collecting signals of this system is high. As a result, the required dose of ICG can be lower to 1/10 times of the dose usually used in hospitals. There are three major advantages of the reduction of the ICG dose. First, in terms of technique, the ICG fluorescence intensity is linearly dependent on the ICG concentration when the dose is as low as 0.116 mg/dl, and that improves the accuracy of assessment. Second, lower dose brings lower cost, saving the usage of expensive ICG is equivalent to reducing the cost. Third, lower ICG dose is less toxic to human body, therefore the assessment can be more safe. We anticipate this method in the future can be further applied not only to the hepatic assessment before liver resection surgery, but also to the postoperative evaluation of the effectiveness of liver transplant or resection surgery.