Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response

Abstract

Background: 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. 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.Results: Quantified 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. Conclusions: Quantification 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.

The Peripheral Blood Transcriptome Is Correlated With PET Measures of Lung Inflammation During Successful Tuberculosis Treatment

“…We found a significant decrease in the average [ 18 F]FDG uptake levels as represented by MSLA, over time, during PTB treatment ( Figure S2 ). MSLA is a PET metric, previously used to calculate [ 18 F]FDG lung lesion activity, and was reported to correlate with changes in lung inflammation ( 16 , 57 ). To identify genes with expression levels in correlation with MSLA levels, over time, we used Model 2.…”

“…We had PET-CT scan data at time points Dx, W04 and W24 for 75 “Cured” subjects, whose RNA-seq data were available ( Table 1 ). In previous studies ( 57 , 58 ), mean standardized lesion activity (MSLA) was one of the quantified PET metrics. MSLA is a normalized mean intensity of [ 18 F]FDG uptake in the area of the lung above a background threshold, computed as Z-score ( 58 ).…”

“…MSLA was also characterized by large variance ( Figure S2 ), hence we included it in our models as an outcome variable. MSLA is a PET metric, previously used to calculate [ 18 F]FDG lung lesion activity, and was reported to correlate with changes in lung inflammation ( 16 , 57 ). It should be noted that few subjects had MSLA of 0 at the end of treatment, and that most (67 of 75) of the PET-CT scans were considered not resolved at the end of treatment.…”

Investigating Non-sterilizing Cure in TB Patients at the End of Successful Anti-TB Therapy

“…Patients were scanned 1 h after the injection using a Philips Gemini scanner. Whole lung analysis was performed on the scans to quantify (1) the total glycolytic activity index (TGAI) on PET (indicating total inflammatory burden) using lesion-free lung as a background (Malherbe et al, 2018 , 2020 ), (2) the most intense residual lesion uptake on PET, (3) the total residual cavity volume on CT.…”

Visualizing the dynamics of tuberculosis pathology using molecular imaging

“…Molecular imaging can also benefit clinical research. Although not specific for TB, 18 F-FDG PET/CT could be used to screen eligible subjects in clinical trials, determine disease heterogeneity to correctly randomize patients between intervention groups, monitor treatment effects, and help predict outcomes ( 20 , 107 , 108 ). However, a standardized methodology to analyze and represent imaging findings should be implemented to allow accurate comparisons between different studies.…”