Advances and Challenges in Molecular Imaging of Viral Infections

Abstract

Molecular imaging of viral infection, using a variety of advanced imaging techniques such as optical and nuclear imaging, can and has been used for direct visualization of the virus as well as assessment of virus-host interactions. Unlike imaging of other pathogens such as bacteria and fungi, challenging aspects of imaging viral infections include the small size of viruses, the complexity of viral infection animal models (eg, species dependence), and the high-level containment needs for many high-consequence pathogens, among others. In this review, using representative viral infections, we discuss how molecular imaging can reveal real-time infection dynamics, improve our understanding of disease pathogenesis, and guide optimization of treatment and prevention strategies. Key findings from human and animal studies are highlighted.

Keywords: Ebola; HIV; PET scan; RSV; high-consequence infection; influenza; molecular imaging; reporter virus; viral infection.

Figure 1.

Molecular imaging of viral infections: To better understand the mechanism of viral infection and host response, an established or newly developed animal model for the virus in question is paired with an appropriate molecular imaging modality. Considerations related to biosafety levels and availability of the animal models are necessary. A successful combination can provide valuable information related to the pathogen itself as well as the host-pathogen interaction and consequences. Using molecular imaging significantly decreases the number of animals needed compared to standard experimental approaches and each animal becomes its own control, thus decreasing variability across experiments. Abbreviations: EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; LASV, Lassa virus; MERS, Middle East respiratory syndrome; PET, positron-emission tomography; RSV, respiratory syncytial virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

A and B, Optical imaging of bioluminescent and fluorescent reporter genes (eg, luciferase, nanoluciferase, green fluorescent protein) enables longitudinal studies of viral infections in a minimum number of animals. C, This allows for visualization, characterization, and quantification of viruses and their dynamics (adapted with permission from Tran et al [5]). Abbreviation: CCD, charge coupled device; dpi, days postinfection.

Figure 3.

Quantifiable opportunistic disease burden in an ART-naive person with HIV before and after treatment with ART. A, ¹⁸F-FDG PET imaging allows assessment of hypermetabolism associated with the infectious process (pulmonary tuberculosis) and (B) response to antiretroviral and antimycobacterial therapy. In this case total glycolytic activity of mediastinal and hilar lymph nodes decreased by almost 18-fold, consistent with response to treatment. Abbreviations: ART, antiretroviral therapy; ¹⁸F-FDG PET, ¹⁸F- fludeoxyglucose positron-emission tomography; SUV, standardized uptake value; TGA, total glycolytic activity.

Figure 4.

A, ¹⁸F-FES PET/CT coronal lung images from SARS-CoV-2–infected hamsters at preinfection (day −1) and infection (day 7). B, Time activity curves show tissue/blood SUV ratios greater during infection versus preinfection. C, Hamster lung immunohistochemistry showing colocalization of S and ERα immunoreactivity (adapted with permission from Solis et al [52]). Abbreviations: E2, estradiol; ¹⁸F-FES, ¹⁸F-estradiol; Erα, estrogen receptor α; PET/CT, positron-emission tomography/computed tomography; S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SUVr, standardized uptake value ratio of tissue to blood.

Figure 5.

¹⁸F-DPA-714 binding in Ebola virus infection. Representative positron-emission tomography/computed tomography (PET/CT) images show ¹⁸F-DPA-714 binding in the (A) lungs (coronal plane), (B) spleen (axial plane), and (C) bone marrow (sagittal plane) of macaques at pre-infection baseline (left) and the terminal stages (right) after infection with the Ebola virus.