Optical Imaging Technologies for Detection of Pulmonary Tuberculosis

Kristen Maitland, PhD

Associate Professor of Biomedical Engineering

Director Microscopy & Imaging Center

Texas A&M University

Abstract: Tuberculosis afflicts one third of the population and is one of the top ten causes of death in children worldwide. Rapid diagnostics and more effective therapeutics are urgently needed. However, the slow growth rate of Mycobacterium tuberculosis, the causative agent of tuberculosis, hinders advancement in all areas of TB research. Fluorescent proteins have been widely utilized in real-time imaging of tuberculosis to track disease progression and evaluate therapeutic outcomes in preclinical models, but the sensitivity of this technique is limited by tissue absorption of fluorescence excitation light particularly in the visible wavelengths. To circumvent the impact of tissue absorption of excitation light, we have applied a fiber bundle microendoscope to deliver fluorescence excitation light directly into the mouse lung. By integrating this microendoscope into a whole animal imaging system to enable intravital excitation in the mouse lung combined with whole animal detection, we have improved the detection threshold of tdTomato expressing M. bovis BCG strain during pulmonary infection to ~1000 colony forming units (CFU). This detection threshold represents a ~3-fold improvement compared to epi-illumination in a whole animal imaging system. Translating towards sensing clinical strains of M. tuberculosis, we utilize reporter enzyme fluorescence technology designed to be cleaved by the BlaC β-lactamase enzyme. Using this near-infrared fluorescent probe, we have increased sensitivity by 10x to 100 CFU mycobacteria in pulmonary infection in mice. Additionally, we developed a computer model of light transport in infected mouse lungs and three-dimensional tissue phantoms that validate the experimental results. By extrapolating the computer model to pediatric infection, we can predict feasibility of optical detection of clinically-relevant TB infection in children.

Bio: Dr. Kristen Maitland is an Associate Professor of Biomedical Engineering and the Director of the Microscopy and Imaging Center at Texas A&M University. She has been awarded the NSF CAREER Award, TEES Select Young Faculty Award, Tenneco Meritorious Teaching Award, and William Keeler Memorial Award for outstanding contributions to the field of engineering. She is a Fellow of the American Institute for Medical and Biological Engineering and SPIE, the international society for optics and photonics, and was elected to the SPIE Board of Directors in 2015 and 2018. Dr. Maitland’s research focuses on the development of light-based technologies for detection, diagnosis, and treatment of disease. Dr. Maitland received her B.S. and M.S. degrees in Electrical Engineering from Cal Poly, San Luis Obispo, and Ph.D. degree in Biomedical Engineering from The University of Texas at Austin.