Quantitative analysis of COVID-19 associated inflammation using FDG-PET/CT

Introduction: The pathogenesis of Coronavirus Disease 2019 (COVID-19) involves the cytokine-driven recruitment and accumulation of inflammatory cells at sites of infection. These activated neutrophils, monocytes, and effector T cells are highly glycolytic and appear as [18] F-labeled fluorodeoxyglucose (FDG) avid sites on positron emission tomography (PET) imaging. With COVID-19 cases at an all-time high and the effectiveness of specific treatments and vaccinations under active investigation, the standardized, quantitative data provided by FDG-PET/CT may be of considerable clinical utility. In this review, we examine the use of FDG-PET/CT in the management of acute and chronic COVID-19 infection and highlight our methodology for quantifying COVID-19 associated inflammation.

Methods: Multiple databases including but not limited to Google Scholar and PubMed were accessed to compile a comprehensive body of literature related to FDG-PET imaging of COVID-19. Studies that examined the use of FDG-PET/CT in other inflammatory and infectious diseases were also referenced.

Results: Early reports suggest that FDG-PET/Computed Tomography (FDG-PET/CT) is a highly sensitive modality for the detection and assessment of COVID-19 disease activity that may hold significant advantages when compared to traditional anatomical imaging techniques. FDG-PET/CT is employed regularly in thoracic oncology, particularly in target delineation for radiation therapy and early detection of related cardiovascular-pulmonary complications. The role of FDG-PET imaging in the detection and characterization of inflammatory disorders has been validated in many settings including chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD).

The leading quantitative assessment methodology involves the integrated analysis of structural volume measurements from imaging techniques like CT and MRI with molecular disease activity measurements provided by PET to generate volumetric parameters and global disease scores (GDS). These quantifications methods can be applied locally to specific organ parenchyma and vessels or globally to quantify the overall degree of functional activity in normal and disease states with high sensitivity compared to conventional measurements. Additionally, total-body FDG-PET imaging generates data that can be quickly translated into a highly reproducible, operator-independent, artificial intelligence (AI) based measurement of GDS. The GDS reflects the total disease burden at the time of the PET examination and can be followed longitudinally to monitor disease activity and response to treatment. Total-body FDG-PET imaging may also allow for early detection of venous thromboembolism, a feared complication of severe COVID-19 infection.

These advantages have led several authors to call for the use of FDG-PET/CT imaging in severe and chronic COVID-19 infection. Our group is currently conducting a prospective trial examining the cardiovascular and pulmonary complications of COVID-19 infection including pneumonitis, vasculitis, and myocarditis with FDG-PET/CT quantitative assessment techniques.

Conclusions: While valid concerns related to cost, radiation burden, and exposure time have limited the application of FDG-PET in COVID-19 patients thus far, FDG-PET/CT imaging has the potential to guide personalized treatment and lead to better characterization of the disease and its systemic complications. Chief advantages of PET include the ability to localize, quantify, and assess local and global inflammatory changes through time for standardized monitoring of disease progression and evaluating response to treatment. Further study is warranted to confirm the substantial value of FDG-PET/CT in the assessment, analysis, and management of COVID-19 infection.