Optimisation of the air fraction correction for lung PET/CT: addressing resolution mismatch.

BACKGROUND: Increased pulmonary [Formula: see text]F-FDG metabolism in patients with idiopathic pulmonary fibrosis, and other forms of diffuse parenchymal lung disease, can predict measurements of health and lung physiology. To improve PET quantification, voxel-wise air fractions (AF) determined from CT can be used to correct for variable air content in lung PET/CT. However, resolution mismatches between PET and CT can cause artefacts in the AF-corrected image. METHODS: Three methodologies for determining the optimal kernel to smooth the CT are compared with noiseless simulations and non-TOF MLEM reconstructions of a patient-realistic digital phantom: (i) the point source insertion-and-subtraction method, [Formula: see text]; (ii) AF-correcting with varyingly smoothed CT to achieve the lowest RMSE with respect to the ground truth (GT) AF-corrected volume of interest (VOI), [Formula: see text]; iii) smoothing the GT image to match the reconstruction within the VOI, [Formula: see text]. The methods were evaluated both using VOI-specific kernels, and a single global kernel optimised for the six VOIs combined. Furthermore, [Formula: see text] was implemented on thorax phantom data measured on two clinical PET/CT scanners with various reconstruction protocols. RESULTS: The simulations demonstrated that at [Formula: see text] iterations (200 i), the kernel width was dependent on iteration number and VOI position in the lung. The [Formula: see text] method estimated a lower, more uniform, kernel width in all parts of the lung investigated. However, all three methods resulted in approximately equivalent AF-corrected VOI RMSEs (<10%) at [Formula: see text]200i. The insensitivity of AF-corrected quantification to kernel width suggests that a single global kernel could be used. For all three methodologies, the computed global kernel resulted in an AF-corrected lung RMSE <10%  at [Formula: see text]200i, while larger lung RMSEs were observed for the VOI-specific kernels. The global kernel approach was then employed with the [Formula: see text] method on measured data. The optimally smoothed GT emission matched the reconstructed image well, both within the VOI and the lung background. VOI RMSE was <10%, pre-AFC, for all reconstructions investigated. CONCLUSIONS: Simulations for non-TOF PET indicated that around 200i were needed to approach image resolution stability in the lung. In addition, at this iteration number, a single global kernel, determined from several VOIs, for AFC, performed well over the whole lung. The [Formula: see text] method has the potential to be used to determine the kernel for AFC from scans of phantoms on clinical scanners.

Investigating the role of platelets and platelet-derived transforming growth factor-ß in idiopathic pulmonary fibrosis.

Transforming growth factor-ß1 (TGFß1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but the primary source of this cytokine in this disease is unknown. Platelets have abundant stores of TGFß1, although the role of these cells in IPF is ill-defined. In this study, we investigated whether platelets, and specifically platelet-derived TGFß1, mediate IPF disease progression. Patients with IPF and non-IPF patients were recruited to determine platelet reactivity, and separate cohorts of patients with IPF were followed for mortality. To study whether platelet-derived TGFß1 modulates pulmonary fibrosis (PF), mice with a targeted deletion of TGFß1 in megakaryocytes and platelets (TGFß1fl/fl.PF4-Cre) were used in the well-characterized bleomycin-induced pulmonary fibrosis (PF) animal model. In a discovery cohort, we found significantly higher mortality in patients with IPF who had elevated platelet counts within the normal range. However, our validation cohort did not confirm this observation, despite significantly increased platelets, neutrophils, active TGFß1, and CCL5, a chemokine produced by inflammatory cells, in the blood, lung, and bronchoalveolar lavage (BAL) of patients with IPF. In vivo, we showed that despite platelets being readily detected within the lungs of bleomycin-treated mice, neither the degree of pulmonary inflammation nor fibrosis was significantly different between TGFß1fl/fl.PF4-Cre and control mice. Our results demonstrate for the first time that platelet-derived TGFß1 does not significantly mediate inflammation or fibrosis in a PF animal model. Furthermore, our human studies revealed blood platelet counts do not consistently predict mortality in IPF but other platelet-derived mediators, such as C-C chemokine ligand 5 (CCL5), may promote neutrophil recruitment and human IPF.NEW & NOTEWORTHY Platelets are a rich source of profibrotic TGFß; however, the role of platelets in idiopathic pulmonary fibrosis (IPF) is unclear. We identified that patients with IPF have significantly more platelets, neutrophils, and active TGFß in their airways than control patients. Using an animal model of IPF, we demonstrated that platelet-derived TGFß does not significantly drive lung fibrosis or inflammation. Our findings offer a better understanding of platelets in both human and animal studies of IPF.

Evolution of 18F-FDG PET/CT Findings in Patients After COVID-19: An Initial Investigation.

The aim of this study was to assess the temporal evolution of pulmonary 18F-FDG uptake in patients with coronavirus disease 2019 (COVID-19) and post-COVID-19 lung disease (PCLD). Methods: Using our hospital's clinical electronic records, we retrospectively identified 23 acute COVID-19, 18 PCLD, and 9 completely recovered 18F-FDG PET/CT patients during the 2 peaks of the U.K. pandemic. Pulmonary 18F-FDG uptake was measured as a lung target-to-background ratio (TBRlung = SUVmax/SUVmin) and compared with temporal stage. Results: In acute COVID-19, less than 3 wk after infection, TBRlung was strongly correlated with time after infection (rs = 0.81, P < 0.001) and was significantly higher in the late stage than in the early stage (P = 0.001). In PCLD, TBRlung was lower in patients treated with high-dose steroids (P = 0.003) and in asymptomatic patients (P < 0.001). Conclusion: Pulmonary 18F-FDG uptake in COVID-19 increases with time after infection. In PCLD, pulmonary 18F-FDG uptake rises despite viral clearance, suggesting ongoing inflammation. There was lower pulmonary 18F-FDG uptake in PCLD patients treated with steroids.

Update in diagnosis and management of interstitial lung disease .

The field of interstitial lung disease (ILD) has undergone significant evolution in recent years, with an increasing incidence and more complex, ever expanding disease classification. In their most severe forms, these diseases lead to progressive loss of lung function, respiratory failure and eventually death. Despite notable advances, progress has been challenged by a poor understanding of pathological mechanisms and patient heterogeneity, including variable progression. The diagnostic pathway is thus being continually refined, with the introduction of tools such as transbronchial cryo lung biopsy and a move towards genetically aided, precision medicine. In this review, we focus on how to approach a patient with ILD and the diagnostic process.

Update in diagnosis and management of interstitial lung disease.

The field of interstitial lung disease (ILD) has undergone significant evolution in recent years, with an increasing incidence and more complex, ever expanding disease classification. In their most severe forms, these diseases lead to progressive loss of lung function, respiratory failure and eventually death. Despite notable advances, progress has been challenged by a poor understanding of pathological mechanisms and patient heterogeneity, including variable progression. The diagnostic pathway is thus being continually refined, with the introduction of tools such as transbronchial cryo lung biopsy and a move towards genetically aided, precision medicine. In this review, we focus on how to approach a patient with ILD and the diagnostic process.