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. 2014 Oct;55(10):1726-9.
doi: 10.2967/jnumed.114.144634. Epub 2014 Jul 31.

Imaging the evolution of reactivation pulmonary tuberculosis in mice using 18F-FDG PET

Allison M Murawski  1 , Saumya Gurbani  2 , Jamie S Harper  1 , Mariah Klunk  3 , Laurent Younes  2 , Sanjay K Jain  1 , Bruno M Jedynak  2
Affiliations

Imaging the evolution of reactivation pulmonary tuberculosis in mice using 18F-FDG PET

Allison M Murawski et al. J Nucl Med. 2014 Oct.

Abstract

Latent tuberculosis infection affects one third of the world's population and can reactivate (relapse) decades later. However, current technologies, dependent on postmortem analyses, cannot follow the temporal evolution of disease.

Methods: C3HeB/FeJ mice, which develop necrotic and hypoxic tuberculosis lesions, were aerosol-infected with Mycobacterium tuberculosis. PET and CT were used to serially image the same cohort of infected mice through pretreatment, tuberculosis treatment, and subsequent development of relapse.

Results: A novel diffeomorphic registration was successfully used to monitor the spatial evolution of individual pulmonary lesions. Although most lesions during relapse developed in the same regions as those noted during pretreatment, several lesions also arose de novo within regions with no prior lesions.

Conclusion: This study presents a novel model that simulates infection and reactivation disease as seen in humans and could prove valuable to study tuberculosis pathogenesis and evaluate novel therapeutics.

Keywords: diffeomorphic registration; latent; mouse; reactivation; tuberculosis.

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Figures

FIGURE 1
FIGURE 1
Timeline showing tuberculosis (TB) infection, incubation, treatment, and 12-wk relapse period. Infected mice were imaged with 18F-FDG PET/CT at specific time points (blue arrows).
FIGURE 2
FIGURE 2
Three-dimensional template with lung regions defined for this study corresponding to lobes: right upper (region 1), right middle and lower (region 2), left upper (region 3), and left lower (region 4). L = left; R = right.
FIGURE 3
FIGURE 3
Transverse, sagittal, coronal, and 3-dimensional PET images of a representative M. tuberculosis–infected mouse corrected for spatial orientation during pretreatment and relapse. Lesion (above defined PET threshold) is shown in yellow. L = left; R = right.
FIGURE 4
FIGURE 4
Box plots showing PLV for each lung region during pretreatment and relapse. Although observed PLVs are similar to expected PLV during pretreatment and relapse in regions 2 and 3, PLVs are significantly higher in regions 1 (pretreatment) and 4 (relapse) (Wilcoxon test, P < 0.01). Data from 15 M. tuberculosis–infected mice are shown. Blue line indicates expected PLV for each region. Solid lines represent mean ± SD.
See this image and copyright information in PMC

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