Laser absorption spectroscopy for the detection of lung cancer biomarkers in exhaled breath
Loading...
Date
2021-10
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of New Brunswick
Abstract
Early diagnosis of lung cancer greatly improves the likelihood of survival and remission, but limitations in existing technologies like low-dose computed tomography have prevented the implementation of widespread screening programs. Breath-based solutions that seek disease biomarkers in exhaled volatile organic compound (VOC) profiles show promise as affordable, accessible, and non-invasive alternatives to traditional imaging. In this thesis, a lung cancer detection framework using cavity ring-down spectroscopy (CRDS), an effective and practical laser absorption spectroscopy technique that has the ability to advance breath screening into clinical reality, is proposed. The main aims of this thesis were to 1) test the utility of infrared CRDS breath profiles for discriminating lung cancer patients from controls, 2) compare models with VOCs as predictors to those with patterns from the CRDS spectra (breathprints), and 3) present a robust approach for identifying relevant lung cancer biomarkers.
First, based on a proposed learning curve technique that estimated the limits of a model’s performance at multiple sample sizes (n = 10−158), the CRDS-based models developed in this work were found to achieve classification performance comparable or superior to corresponding mass spectroscopy and sensor-based systems.
Second, using 158 collected samples (62 non-small cell lung cancer subjects and 96 controls), the accuracy range for the VOC-based model was 65.19% − 85.44% (51.61% − 66.13% sensitivity and 73.96% − 97.92% specificity), depending on the employed cross-validation technique. The model based on breathprint predictors generally performed better, with accuracy ranging from 71.52% − 86.08% (58.06% − 82.26% sensitivity and 80.21% − 88.54% specificity).
Lastly, using a protocol based on consensus feature selection, three VOCs (isopropanol, dimethyl sulfide, and butyric acid) and two breathprint features (from a local binary pattern transformation of the spectra) were identified as possible lung cancer biomarkers.
This research demonstrates the potential of infrared CRDS breath profiles and the developed early-stage classification techniques for lung cancer biomarker detection and screening.