Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules.

INTRODUCTION: Dynamic contrast-enhanced CT (DCE-CT) and positron emission tomography/CT (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules (SPNs). The aim of this study was to compare the accuracy and cost-effectiveness of these. METHODS: In this prospective multicentre trial, 380 participants with an SPN (8-30 mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. RESULTS: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% (95% CI 91.3 to 97.5), 29.8% (95% CI 22.3 to 38.4), 68.2% (95% CI 62.4% to 73.5%) and 80.0% (95% CI 66.2 to 89.1), respectively, and for PET/CT were 79.1% (95% CI 72.7 to 84.2), 81.8% (95% CI 74.0 to 87.7), 87.3% (95% CI 81.5 to 91.5) and 71.2% (95% CI 63.2 to 78.1). The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 (95% CI 0.58 to 0.67) and 0.80 (95% CI 0.76 to 0.85), respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 (95% CI 0.86 to 0.93), p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15 500 a combined approach was preferred. CONCLUSIONS: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of SPNs. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. TRIAL REGISTRATION NUMBER: NCT02013063.

Validation of a combined image derived input function and venous sampling approach for the quantification of [18F]GE-179 PET binding in the brain.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of -1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias -20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.

FDG-PET/CT in colorectal cancer: potential for vascular-metabolic imaging to provide markers of prognosis.

PURPOSE: This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. METHODS: This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. RESULTS: A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon - high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441-8.333), p = 0.006; M0rectum - high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901-10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162-5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants. CONCLUSION: Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility.

CT texture-based radiomics analysis of carotid arteries identifies vulnerable patients: a preliminary outcome study.

PURPOSE: To assess the potential role of computed tomography (CT) texture analysis (CTTA) in identifying vulnerable patients with carotid artery atherosclerosis. METHODS: In this case-control pilot study, 12 patients with carotid atherosclerosis and a subsequent history of transient ischemic attack or stroke were age and sex matched with 12 control cases with asymptomatic carotid atherosclerosis (follow-up time 103.58 ± 9.2 months). CTTA was performed using a commercially available research software package (TexRAD) by an operator blinded to clinical data. CTTA comprised a filtration-histogram technique to extract features at different scales corresponding to spatial scale filter (fine = 2 mm, medium = 3 mm, coarse = 4 mm), followed by quantification using histogram-based statistical parameters: mean, kurtosis, skewness, entropy, standard deviation, and mean value of positive pixels. A single axial slice was selected to best represent the largest cross-section of the carotid bifurcation or the greatest degree of stenosis, in presence of an atherosclerotic plaque, on each side. RESULTS: CTTA revealed a statistically significant difference in skewness between symptomatic and asymptomatic patients at the medium (0.22 ± 0.35 vs - 0.18 ± 0.39, p < 0.001) and coarse (0.23 ± 0.22 vs 0.03 ± 0.29, p = 0.003) texture scales. At the fine-texture scale, skewness (0.20 ± 0.59 vs - 0.18 ± 0.58, p = 0.009) and standard deviation (366.11 ± 117.19 vs 300.37 ± 82.51, p = 0.03) were significant before correction. CONCLUSION: Our pilot study highlights the potential of CTTA to identify vulnerable patients in stroke and TIA. CT texture may have the potential to act as a novel risk stratification tool in patients with carotid atherosclerosis.

The role of PET in imaging of the tumour microenvironment and response to immunotherapy.

Positron emission tomography (PET) is an exquisitely sensitive molecular imaging technique with broad utility in cancer diagnosis and monitoring. Many ligands labelled with positron-emitting isotopes have been developed that are of interest in the field of cancer imaging. This review intends to provide an overview and outlook of PET in the field of oncology using radiotracers beyond that of the now widespread 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG). A particular focus is the role of PET in understanding and monitoring the tumour microenvironment (TME) in response to chemo-radiotherapy. Furthermore priority will be given to aspects where PET has provided for monitoring of the immune response to cancer including the expanding field of cancer immunotherapy and in the arena of theranostics. The development of new techniques from both preclinical and human studies will be included to give a perspective on future directions, thereby helping to illustrate the importance of PET in cancer patient management.

A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis.

Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics. Omipalisib was dosed at 0.25 mg, 1 mg and 2 mg twice daily for 8 days in four cohorts of four subjects randomised 3:1 to receive omipalisib or placebo (two cohorts received 2 mg twice daily).17 subjects with IPF were enrolled. The most common adverse event was diarrhoea, which was reported by four participants. Dose-related increases in insulin and glucose were observed. Pharmacokinetic analysis demonstrated that exposure in the blood predicts lung exposure. Exposure-dependent inhibition of phosphatidylinositol 3,4,5 trisphosphate and pAKT confirmed target engagement in blood and lungs. 18F-2-fluoro-2-deoxy-d-glucose(FDG)-positron emission tomography/computed tomography scans revealed an exposure-dependent reduction in 18F-FDG uptake in fibrotic areas of the lung, as measured by target-to-background, ratio thus confirming pharmacodynamic activity.This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.

Synergistic application of pulmonary 18F-FDG PET/HRCT and computer-based CT analysis with conventional severity measures to refine current risk stratification in idiopathic pulmonary fibrosis (IPF).

INTRODUCTION: To investigate the combined performance of quantitative CT (qCT) following a computer algorithm analysis (IMBIO) and 18F-FDG PET/CT to assess survival in patients with idiopathic pulmonary fibrosis (IPF). METHODS: A total of 113 IPF patients (age 70 ± 9 years) prospectively and consecutively underwent 18F-FDG PET/CT and high-resolution CT (HRCT) at our institution. During a mean follow-up of 29.6 ± 26 months, 44 (48%) patients died. As part of the qCT analysis, pattern evaluation of HRCT (using IMBIO software) included the total extent (percentage) of the following features: normal-appearing lung, hyperlucent lung, parenchymal damage (comprising ground-glass opacification, reticular pattern and honeycombing), and the pulmonary vessels. The maximum (SUVmax) and minimum (SUVmin) standardized uptake value (SUV) for 18F-FDG uptake in the lungs, and the target-to-background (SUVmax/SUVmin) ratio (TBR) were quantified using routine region-of-interest (ROI) analysis. Pulmonary functional tests (PFTs) were acquired within 14 days of the PET/CT/HRCT scan. Kaplan-Meier (KM) survival analysis was used to identify associations with mortality. RESULTS: Data from 91 patients were available for comparative analysis. The average ± SD GAP [gender, age, physiology] score was 4.2 ± 1.7 (range 0-8). The average ± SD SUVmax, SUVmin, and TBR were 3.4 ± 1.4, 0.7 ± 0.2, and 5.6 ± 2.8, respectively. In all patients, qCT analysis demonstrated a predominantly reticular lung pattern (14.9 ± 12.4%). KM analysis showed that TBR (p = 0.018) and parenchymal damage assessed by qCT (p = 0.0002) were the best predictors of survival. Adding TBR and qCT to the GAP score significantly increased the ability to differentiate between high and low risk (p < 0.0001). CONCLUSION: 18F-FDG PET and qCT are independent and synergistic in predicting mortality in patients with IPF.

Magnetic Resonance Texture Analysis in Identifying Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer.

BACKGROUND: A certain proportion of patients with locally advanced rectal cancer experience complete response after undergoing neoadjuvant chemoradiotherapy. These patients might be suitable for a conservative "watch and wait" approach, avoiding high-morbidity surgery. Texture analysis is a new modality that can assess heterogeneity in medical images by statistically analyzing gray-level intensities on a pixel-by-pixel basis. This study hypothesizes that texture analysis of magnetic resonance images can identify patients with a complete response. OBJECTIVE: This study aims to determine whether texture analysis of magnetic resonance images as a quantitative imaging biomarker can accurately identify patients with complete response. DESIGN: This is a retrospective diagnostic accuracy study. SETTINGS: This study was conducted at Colchester General Hospital, January 2003 to 2014. PATIENTS: All patients diagnosed with locally advanced rectal cancer who underwent long-course chemoradiotherapy had a posttreatment magnetic resonance scan and underwent surgery are included. INTERVENTION: Texture analysis was extracted from T2-weighted magnetic resonance images of the rectal cancer. MAIN OUTCOME MEASURES: Textural features that are able to identify complete responders were identified by a Mann-Whitney U test. Their diagnostic accuracy in identifying complete responders was determined by the area under the receiver operator characteristics curve. Cutoff values were determined by the Youden index. Pathology was the standard of reference. RESULTS: One hundred fourteen patients with first posttreatment MRI scans (6.2 weeks after completion of neoadjuvant treatment) were included. Sixty-eight patients had a second posttreatment scan (10.4 weeks). With no filtration, mean (p = 0.033), SD (p = 0.048), entropy (p = 0.007), and skewness (p = 0.000) from first posttreatment scans, and SD (p = 0.042), entropy (p = 0.014), mean of positive pixels (p = 0.032), and skewness (p = 0.000) from second posttreatment scans were all able to identify complete response. Area under the curve ranged from 0.750 to 0.88. LIMITATIONS: Texture analysis of MRI is a new modality; therefore, further studies are necessary to standardize the methodology of extraction of texture features, timing of scans, and acquisition parameters. CONCLUSIONS: Texture analysis of MRI is a potentially significant imaging biomarker that can accurately identify patients who have experienced complete response and might be suitable for a nonsurgical approach. (Cinicaltrials.gov:NCT02439086). See Video Abstract at http://links.lww.com/DCR/A760.

Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF).

PURPOSE: There 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. METHODS: A 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. RESULTS: During 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. CONCLUSIONS: A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

Streamlining staging of lung and colorectal cancer with whole body MRI; study protocols for two multicentre, non-randomised, single-arm, prospective diagnostic accuracy studies (Streamline C and Streamline L).

BACKGROUND AND AIMS: Rapid and accurate cancer staging following diagnosis underpins patient management, in particular the identification of distant metastatic disease. Current staging guidelines recommend sequential deployment of various imaging platforms such as computerised tomography (CT) and positron emission tomography (PET) which can be time and resource intensive and onerous for patients. Recent studies demonstrate that whole body magnetic resonance Imaging (WB-MRI) may stage cancer efficiently in a single visit, with potentially greater accuracy than current staging investigations. The Streamline trials aim to evaluate whether WB-MRI increases per patient detection of metastases in non-small cell lung and colorectal cancer compared to standard staging pathways. METHODS: The Streamline trials are multicentre, non-randomised, single-arm, prospective diagnostic accuracy studies with a novel design to capture patient management decisions during staging pathways. The two trials recruit adult patients with proven or highly suspected new diagnosis of primary colorectal (Streamline C) or non-small cell lung cancer (Streamline L) referred for staging. Patients undergo WB-MRI in addition to standard staging investigations. Strict blinding protocols are enforced for those interpreting the imaging. A first major treatment decision is made by the multi-disciplinary team prior to WB-MRI revelation based on standard staging investigations only, then based on the WB-MRI and any additional tests precipitated by WB-MRI, and finally based on all available test results. The reference standard is derived by a multidisciplinary consensus panel who assess 12 months of follow-up data to adjudicate on the TNM stage at diagnosis. Health psychology assessment of patients' experiences of the cancer staging pathway will be undertaken via interviews and questionnaires. A cost (effectiveness) analysis of WB-MRI compared to standard staging pathways will be performed. DISCUSSION: We describe a novel approach to radiologist and clinician blinding to ascertain the 'true' diagnostic accuracy of differing imaging pathways and discuss our approach to assessing the impact of WB-MRI on clinical decision making in real-time. The Streamline trials will compare WB-MRI and standard imaging pathways in the same patients, thereby informing the most accurate and efficient approach to staging. TRIAL REGISTRATION: Streamline C ISRCTN43958015 (registered 25/7/2012). Streamline L ISRCTN50436483 (registered 31/7/2012).

MRI texture analysis (MRTA) of T2-weighted images in Crohn's disease may provide information on histological and MRI disease activity in patients undergoing ileal resection.

OBJECTIVES: To associate MRI textural analysis (MRTA) with MRI and histological Crohn's disease (CD) activity. METHODS: Sixteen patients (mean age 39.5 years, 9 male) undergoing MR enterography before ileal resection were retrospectively analysed. Thirty-six small (≤3 mm) ROIs were placed on T2-weighted images and location-matched histological acute inflammatory scores (AIS) measured. MRI activity (mural thickness, T2 signal, T1 enhancement) (CDA) was scored in large ROIs. MRTA features (mean, standard deviation, mean of positive pixels (MPP), entropy, kurtosis, skewness) were extracted using a filtration histogram technique. Spatial scale filtration (SSF) ranged from 2 to 5 mm. Regression (linear/logistic) tested associations between MRTA and AIS (small ROIs), and CDA/constituent parameters (large ROIs). RESULTS: Skewness (SSF = 2 mm) was associated with AIS [regression coefficient (rc) 4.27, p = 0.02]. Of 120 large ROI analyses (for each MRI, MRTA feature and SSF), 15 were significant. Entropy (SSF = 2, 3 mm) and kurtosis (SSF = 3 mm) were associated with CDA (rc 0.9, 1.0, -0.45, p = 0.006-0.01). Entropy and mean (SSF = 2-4 mm) were associated with T2 signal [odds ratio (OR) 2.32-3.16, p = 0.02-0.004], [OR 1.22-1.28, p = 0.03-0.04]. MPP (SSF = 2 mm) was associated with mural thickness (OR 0.91, p = 0.04). Kurtosis (SSF = 3 mm), standard deviation (SSF = 5 mm) were associated with decreased T1 enhancement (OR 0.59, 0.42, p = 0.004, 0.007). CONCLUSIONS: MRTA features may be associated with CD activity. KEY POINTS: • MR texture analysis features may be associated with Crohn's disease histological activity. • Texture analysis features may correlate with MR-dependent Crohn's disease activity scores. • The utility of MR texture analysis in Crohn's disease merits further investigation.

"Textural analysis of multiparametric MRI detects transition zone prostate cancer".

OBJECTIVES: To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour. METHODS: Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis. RESULTS: ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83). CONCLUSION: Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion. KEY POINTS: • MR textural features of prostate transition zone may discriminate significant prostatic cancer. • Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram. • TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity. • The utility of MR texture analysis in prostate cancer merits further investigation.

Defining left ventricular remodeling following acute ST-segment elevation myocardial infarction using cardiovascular magnetic resonance.

BACKGROUND: The assessment of post-myocardial infarction (MI) left ventricular (LV) remodeling by cardiovascular magnetic resonance (CMR) currently uses criteria defined by echocardiography. Our aim was to provide CMR criteria for assessing LV remodeling following acute MI. METHODS: Firstly, 40 reperfused ST-segment elevation myocardial infarction (STEMI) patients with paired acute (4 ± 2 days) and follow-up (5 ± 2 months) CMR scans were analyzed by 2 independent reviewers and the minimal detectable changes (MDCs) for percentage change in LV end-diastolic volume (%ΔLVEDV), LV end-systolic volume (%ΔLVESV), and LV ejection fraction (%ΔLVEF) between the acute and follow-up scans were determined. Secondly, in 146 reperfused STEMI patients, receiver operator characteristic curve analyses for predicting LVEF <50% at follow-up (as a surrogate for clinical poor clinical outcome) were undertaken to obtain cut-off values for %ΔLVEDV and %ΔLVESV. RESULTS: The MDCs for %ΔLVEDV, %ΔLVESV, and %ΔLVEF were similar at 12%, 12%, 13%, respectively. The cut-off values for predicting LVEF < 50% at follow-up were 11% for %ΔLVEDV on receiver operating characteristic curve analysis (area under the curve (AUC) 0.75, 95% CI 0.6 to 0.83, sensitivity 72% specificity 70%), and 5% for %ΔLVESV (AUC 0.83, 95% CI 0.77 to 0.90, sensitivity and specificity 78%). Using cut-off MDC values (higher than the clinically important cut-off values) of 12% for both %ΔLVEDV and %ΔLVESV, 4 main patterns of LV remodeling were identified in our cohort: reverse LV remodeling (LVEF predominantly improved); no LV remodeling (LVEF predominantly unchanged); adverse LV remodeling with compensation (LVEF predominantly improved); and adverse LV remodeling (LVEF unchanged or worsened). CONCLUSIONS: The MDCs for %ΔLVEDV and %ΔLVESV between the acute and follow-up CMR scans of 12% each may be used to define adverse or reverse LV remodeling post-STEMI. The MDC for %ΔLVEF of 13%, relative to baseline, provides the minimal effect size required for investigating treatments aimed at improving LVEF following acute STEMI.

Non-small-cell lung cancer resectability: diagnostic value of PET/MR.

PURPOSE: To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. METHODS: Fifty consecutive consenting patients who underwent routine (18)F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. RESULTS: ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). CONCLUSION: In lung cancer patients PET/MR appears to be a robust technique for preoperative staging.

T1 mapping and T2 mapping at 3T for quantifying the area-at-risk in reperfused STEMI patients.

BACKGROUND: Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study. METHODS: 18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4-6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed. RESULTS: A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 ± 0.26 versus 0.39 ± 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R(2) of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R(2) 0.95, P < 0.0001, bias 0.7 ± 5.1 %). CONCLUSIONS: T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR.

Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients.

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.

Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting.

BACKGROUND: 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of increased metabolic activity. FDG uptake differs between areas of normal lung parenchyma and interstitial lung disease (ILD). OBJECTIVES: In this study, we investigated whether FDG-PET/CT parameters were associated with a change in the quality of life (QoL) in patients with ILD over 4 years of follow-up. METHODS: Patients underwent PET-CT imaging at diagnosis and were followed up with annual QoL assessment using the St George's Respiratory Questionnaire (SGRQ) until death or 4 years of follow-up. Maximum standard uptake value (SUVmax) and Tissue-to-Background Ratio (TBR) were assessed against SGRQ overall and subscale scores. RESULTS: 193 patients (94 patients in the idiopathic pulmonary fibrosis (IPF) subgroup and 99 patients in the non-IPF subgroup) underwent baseline FDG-PET/CT imaging and QoL assessment. Weak-to-moderate correlation was observed between baseline SUVmax and SGRQ scores in both ILD subgroups. No relationship was observed between baseline SUVmax or TBR and change in SGRQ scores over 4 years of follow-up. In the IPF subgroup, surviving patients reported a decline in QoL at 4 years post diagnosis whereas an improvement in QoL was seen in surviving patients with non-IPF ILD. CONCLUSIONS: Weak-to-moderate positive correlation between baseline SUVmax and SGRQ scores was observed in both ILD subgroups (IPF:rs=0.187, p=0.047, non-IPF: rs=0.320, p=0.001). However, baseline SUVmax and TBR were not associated with change in QoL in patients with IPF and non-IPF ILD over 4 years of follow-up. At 4 years post diagnosis, surviving patients with IPF reported declining QoL whereas improvement was seen in patients with ILD who did not have IPF.