Positron Emission Tomography-Computed Tomography (PET-CT) has shown potential as a research tool to characterise heterogeneity in tuberculosis (TB) infection. Prospective utilisation of this technology will require standardisation of imaging protocols, interpretation and analysis of PET-CT images to improve generalisability and data assimilation between discrete cohorts. We evaluated a semi-automated approach using open-source software to minimise inter-operator variability of imaging interpretation and use reference organ normalisation to lower variability in physiological uptake.

We quantified 18F-Fluorodeoxyglucose (FDG) uptake in intrathoracic lymph nodes (ITLNs) of eleven QuantiFERON-TB Gold-Plus positive TB contacts that enrolled on a prospective observational study, including eight contacts with serial PET-CT scans. The imaging was analysed using 3D Slicer, an open-source medical imaging platform designed for biomedical and clinical research, that provides semi-automated segmentation and automated liver quantification. The extracted data included ITLN maximum standardised uptake value (SUVmax), mean standardised uptake value (SUVmean), metabolic volume (MV), and total lesion glycolysis (TLG), and liver SUVmean. We compared its performance to that of clinical software, both with and without standardising to liver uptake (as a physiological reference), and assessed operator variability. Then, we evaluated the association between multiple quantitative PET metrics and prospective outcomes in pulmonary TB contacts.

We report strong agreement between open-source and clinical image evaluation platforms. We find semi-automated PET quantification can lower inter-operator variability, and standardising to reference organs increases the sensitivity of imaging analysis. Specifically, we report preliminary findings that increasing metabolic activity on serial PET-CT in early infection is associated with detectable Mtb at the anatomical site of FDG uptake, consistent with a progressive phenotype of infection.

The authors have declared no competing interest.

The study was funded by University of Leicester MRC Confidence in Concept award to P.H..

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Research Ethics Committee for East Midlands, Nottingham 1, Nottingham, UK (REC 15/EM/0109).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Requests for additional data not included in the paper will be considered upon request but may be subject to additional ethical review.