Liver Status Assessment by Spectrally and Time Resolved IR Detection of Drug Induced Breath Gas Changes

Abstract

Abstract:The actual metabolic capacity of the liver is crucial for disease identification, liver therapy, and liver tumor resection. By combining induced drug metabolism and high sensitivity IR spectroscopy of exhaled air, we provide a method for quantitative liver assessment at bedside within 20 to 60 min. Fast administration of 13 C-labelled methacetin induces a fast response of liver metabolism and is tracked in real-time by the increase of 13 CO 2 in exhaled air. The 13 CO 2 concentration increase in exhaled air allows the determination of the metabolic liver capacity (LiMAx-test). Fluctuations in CO 2 concentration, pressure and temperature are minimized by special gas handling, and tracking of several spectrally resolved CO 2 absorption bands with a quantum cascade laser. Absorption measurement of different 12 CO 2 and 13 CO 2 rotation-vibration transitions in the same time window allows for multiple referencing and reduction of systematic errors. This FLIP (Fast liver investigation package) setup is being successfully used to plan operations and determine the liver status of patients.

Analysis of Human Breath by Millimeter-Wave/Terahertz Spectroscopy

“…A method based on infrared spectroscopy is already successfully in use to plan liver surgery. With this method, the liver status of patients is determined by the exhaled isotopologue ratio of carbon monoxide after administration and metabolism of a 13 C-labelled methacetin [14]. Breath analysis is also considered as a tool for therapeutic drug monitoring [15].…”

Randomized clinical trial comparing liver resection with and without perioperative assessment of liver function

“…Breath analysis was performed using a novel CE‐certified medical device (FLIP®; Humedics). The entire exhaled breath is collected by a specific face mask (Humedics) and transferred through the FLIP ® device for quantitative real‐time determination of 12 CO 2 and 13 CO 2 concentration using a quantum cascade laser . The LiMAx ® test result (given in micrograms of substrate metabolism per h, normalized to bodyweight) is calculated by the device and provided within 20 min to a maximum of 60 min after substrate administration.…”

A novel variant of the 13C-methacetin liver function breath test that eliminates the confounding effect of individual differences in systemic CO2 kinetics

“…To analyze the whole breath continuously, a specifically designed face mask was used for easy collection of exhaled breath. The gas analyses were performed in real time at the bedside using the commercially available FLIP ® detection device (Humedics GmbH, Berlin, Germany) with a newly developed device for spectral analysis of the 13 CO 2 and 12 CO 2 amounts in the exhaled breath (Rubin et al 2011(Rubin et al , 2016. The intravenous injection of 13 C-labeled bicarbonate (named 13 C-B in the following) was performed after about 10 min when the DOB baseline has reached stable values.…”

“…As individual differences in the intestinal uptake of the test drug may distort the test results, an improved variant of the MBT test (LiMAx test) has been developed at the Charite Berlin based on the intravenous administration of the drug and quasi-continuous monitoring of 13 CO 2 in the breath by means of an ultra-sensitive laser system (Stockmann et al 2009). The LiMAx test has been successfully validated as a valuable non-invasive test in liver surgery for the pre-and postoperative assessment of organ function (Stockmann et al 2009;Rubin et al 2016) and for classifying the risk of cirrhotic complications and mortality in patients evaluated for liver transplantation (Jara et al 2015). Moreover, in a retrospective study encompassing 102 patients with chronic liver disease who underwent a liver biopsy, the LiMAx test performed better than transient elastography (TE) and several serum biomarkers in detecting different stages of liver fibrosis and cirrhosis (Buechter et al 2018).…”