Abstract
BackgroundThere is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes.ResultsQuantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions.ConclusionsQuantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.
Highlights
There is a growing interest in the use of F-18 FDG Positron emission tomography (PET)-X-ray computed tomography (CT) to monitor tuberculosis (TB) treatment response
Factors contributing to the uncertainty of defining sterilising cure include the persistence of radiological lung lesions [17, 18], clinical symptoms, and Mycobacterium tuberculosis (MTB) DNA in sputum [19, 20] after clinical cure
We evaluated the individual components of the total glycolytic activity index (TGAI) (Zmean, the SUVmax, metabolic lesion volume (MLV) —Additional file 1: Figure S3), and high-density lesions on CT (Vhard, vasculature; (3) medium density lesions (Vmedium), Soft lesion volume (Vsoft) —Additional file 1: Figure S4), as well as the intersection of high-density lesions on CT and FDG-avid lesions on PET (MLVabn—Additional file 1: Figure S5)
Summary
There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. Factors contributing to the uncertainty of defining sterilising cure include the persistence of radiological lung lesions [17, 18], clinical symptoms, and Mycobacterium tuberculosis (MTB) DNA in sputum [19, 20] after clinical cure. Researchers, and investors in new therapies urgently require improved methods to better define TB treatment response. This need has triggered an increasing interest in using 18-F fluorodeoxyglucose positron emission tomography-computed tomography (18-F FDG PET-CT) as a research tool in tuberculosis. Due to its high sensitivity for metabolic activity in infectious lesions, it has shown the potential to be a powerful and possibly cost-effective tool in TB trials, despite the reported lack of specificity in diagnosing active TB in high-incidence areas and its dependence on expensive resources [21, 22]
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