Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Chiara Lowe, Ana Ortega-Gil, Mahdieh Moghiseh, Nigel G. Anderson, Arrate Munoz-Barrutia, Juan Jose Vaquero, Aamir Y. Raja, Aysouda Matanaghi, Alexander I. Chernoglazov, Theodorus Dapamede, Sikiru A. Adebileje, Steven Alexander, Maya R. Amma, Marzieh Anjomrouz, Fatemeh Asghariomabad, Ali Atharifard, James Atlas, Kenzie Baer, Stephen T. Bell, Srinidhi BheesettePhilip H. Butler, Pierre Carbonez, Claire Chambers, Krishna M. Chapagain, Jennifer A. Clark, Frances Colgan, Jonathan S. Crighton, Shishir Dahal, Jerome Damet, Niels J.A. De Ruiter, Robert M.N. Doesburg, Neryda Duncan, Nooshin Ghodsian, Steven P. Gieseg, Brian P. Goulter, Sam Gurney, Joseph L. Healy, Praveen Kumar Kanithi, Tracy Kirkbride, Stuart P. Lansley, V. B.H. Mandalika, Emmanuel Marfo, David Palmer, Raj K. Panta, Hannah M. Prebble, Peter Renaud, Yann Sayous, Nanette Schleich, Emily Searle, Jereena S. Sheeja, Lieza Vanden Broeke, V. S. Vivek, E. Peter Walker, Michael F. Walsh, Manoj Wijesooriya, W. Ross Younger, Anthony P.H. Butler

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm3 and 2.83 mm3, respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans.

Original languageBritish English
Article number9419038
Pages (from-to)67201-67208
Number of pages8
JournalIEEE Access
Volume9
DOIs
StatePublished - 2021

Keywords

  • High resolution
  • micro-CT
  • photon-counting spectral CT
  • pulmonary tuberculosis
  • translatable molecular imaging

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