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Purpose Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. Methods Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent 18 F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of 18 F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). Results The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients ( p  < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients ( p  < 0.001). Conclusion IPF patients have increased pulmonary uptake of 18 F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring.

Purpose It has recently been recognized that PET/CT may play a role in diffuse parenchymal lung disease. However, interpretation can be confounded due to the variability in lung density both within and between individuals. To address this issue a novel correction method is proposed. Methods A CT scan acquired during shallow breathing is registered to a PET study and smoothed so as to match the PET resolution. This is used to derive voxel-based tissue fraction correction factors for the individual. The method was evaluated in a lung phantom study in which the lung was simulated by a Styrofoam/water mixture. The method was further evaluated using 18 F-FDG in 12 subjects free from pulmonary disease where ranges before and after correction were considered. Results Correction resulted in similar activity concentrations for the lung and background regions, consistent with the experimental phantom set-up. Correction resulted in reduced inter- and intrasubject variability in the estimated SUV. The possible application of the method was further demonstrated in five subjects with interstitial lung changes where increased SUV was demonstrated. Single study pre- and post-treatment studies were also analysed to further illustrate the utility of the method. Conclusion The proposed tissue fraction correction method is a promising technique to account for variability of density in interpreting lung PET studies.

PurposeThere is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF.MethodsA total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients.ResultsDuring a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.ConclusionsA high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

Objective To determine how commercial software platform upgrades impact on derived parameters for colorectal cancer. Materials and methods Following ethical approval, 30 patients with suspected colorectal cancer underwent Perfusion CT using integrated 64 detector PET/CT before surgery. Analysis was performed using software based on modified distributed parameter analysis (Perfusion software version 4; Perfusion 4.0), then repeated using the previous version (Perfusion software version 3; Perfusion 3.0). Tumour blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined for identical regions-of-interest. Slice-by-slice and ‘whole tumour’ variance was assessed by Bland-Altman analysis. Results Mean BF, BV and PS was 20.4%, 59.5%, and 106% higher, and MTT 14.3% shorter for Perfusion 4.0 than Perfusion 3.0. The mean difference (95% limits of agreement) were +13.5 (−44.9 to 72.0), +2.61 (−0.06 to 5.28), −1.23 (−6.83 to 4.36), and +14.2 (−4.43 to 32.8) for BF, BV, MTT and PS respectively. Within subject coefficient of variation was 36.6%, 38.0%, 27.4% and 60.6% for BF, BV, MTT and PS respectively indicating moderate to poor agreement. Conclusion Software version upgrades of the same software platform may result in significantly different parameter values, requiring adjustments for cross-version comparison.

Purpose Noninvasive markers of disease activity in patients with idiopathic pulmonary fibrosis (IPF) are lacking. We performed this study to investigate the reproducibility of pulmonary 18 F-FDG PET/CT in patients with IPF. Methods The study group comprised 13 patients (11 men, 2 women; mean age 71.1 ± 9.9 years) with IPF recruited for two thoracic 18 F-FDG PET/CT studies performed within 2 weeks of each other. All patients were diagnosed with IPF in consensus at multidisciplinary meetings as a result of typical clinical, high-resolution CT and pulmonary function test features. Three methods for evaluating pulmonary 18 F-FDG uptake were used. The maximal 18 F-FDG pulmonary uptake (SUVmax) in the lungs was determined using manual region-of-interest placement. An 18 F-FDG uptake intensity histogram was automatically constructed from segmented lungs to evaluate the distribution of SUVs. Finally, mean SUV was determined for volumes-of-interest in pulmonary regions with interstitial lung changes identified on CT scans. Processing included correction for tissue fraction effects. Bland-Altman analysis was performed and interclass correlation coefficients (ICC) were determined to assess the reproducibility between the first and second PET scans, as well as the level of intraobserver and interobserver agreement. Results The mean time between the two scans was 6.3 ± 4.3 days. The interscan ICCs for pulmonary SUVmax analysis and mean SUV corrected for tissue fraction effects were 0.90 and 0.91, respectively. Intensity histograms were different in only 1 of the 13 paired studies. Intraobserver agreement was also excellent (0.80 and 0.85, respectively). Some bias was observed between observers, suggesting that serial studies would benefit from analysis by the same observer. Conclusion This study demonstrated that there is excellent short-term reproducibility in pulmonary 18 F-FDG uptake in patients with IPF.

Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid (18)F-FDG PET/CT angiography. Plaque (18)F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. The mean (±SD) surgically excised carotid plaque (18)F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque (18)F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque (18)F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. METHODS: Twenty-one consecutive patients (18 men, 3 women; mean age plus or minus SD, 68.3 plus or minus 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. RESULTS: The mean ( plus or minus SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 ( plus or minus 0.5) versus 2.2 ( plus or minus 0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 ( rho = 0.55; P = 0.011) and vascular endothelial growth factor ( rho = 0.47; P = 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT ( rho = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 ( rho = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. CONCLUSION: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of (18)F-FDG to detect angiogenesis in early breast carcinoma using PET/CT. Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUV(max)) and mean standardized uptake value (SUV(mean)). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1). The SUV(max) showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = -0.16, p = 0.496. The SUV(mean) showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = -0.18, p = 0.443 (18)F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, (18)F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease.

This corrects the article DOI: 10.1038/nature22364.

Nature 545, 446–451 (2017); doi:10.1038/nature22364 For 6 of the 96 patients included in this Article (patients CRUK0014, CRUK0030, CRUK0048, CRUK0059, CRUK0096 and CRUK0097) incorrect tumour volumetric data and positron emission tomography (PET) tumour background ratio (TBR) data were analysed. This error occurred because of the incorrect assignment of patient identifiers during the anonymization mandated by the independent review board of pre-operative computed tomography (CT) scans belonging to these patients.