Development and Validation of Prognostic Models Using Radiomic Features from Pre-Treatment Positron Emission Tomography (PET) Images in Head and Neck Squamous Cell Carcinoma (HNSCC) Patients.

High-dimensional radiomics features derived from pre-treatment positron emission tomography (PET) images offer prognostic insights for patients with head and neck squamous cell carcinoma (HNSCC). Using 124 PET radiomics features and clinical variables (age, sex, stage of cancer, site of cancer) from a cohort of 232 patients, we evaluated four survival models-penalized Cox model, random forest, gradient boosted model and support vector machine-to predict all-cause mortality (ACM), locoregional recurrence/residual disease (LR) and distant metastasis (DM) probability during 36, 24 and 24 months of follow-up, respectively. We developed models with five-fold cross-validation, selected the best-performing model for each outcome based on the concordance index (C-statistic) and the integrated Brier score (IBS) and validated them in an independent cohort of 102 patients. The penalized Cox model demonstrated better performance for ACM (C-statistic = 0.70, IBS = 0.12) and DM (C-statistic = 0.70, IBS = 0.08) while the random forest model displayed better performance for LR (C-statistic = 0.76, IBS = 0.07). We conclude that the ML-based prognostic model can aid clinicians in quantifying prognosis and determining effective treatment strategies, thereby improving favorable outcomes in HNSCC patients.

Comparison of semi-automatic and manual segmentation methods for tumor delineation on head and neck squamous cell carcinoma (HNSCC) positron emission tomography (PET) images.

Objective. Accurate and reproducible tumor delineation on positron emission tomography (PET) images is required to validate predictive and prognostic models based on PET radiomic features. Manual segmentation of tumors is time-consuming whereas semi-automatic methods are easily implementable and inexpensive. This study assessed the reliability of semi-automatic segmentation methods over manual segmentation for tumor delineation in head and neck squamous cell carcinoma (HNSCC) PET images.Approach. We employed manual and six semi-automatic segmentation methods (just enough interaction (JEI), watershed, grow from seeds (GfS), flood filling (FF), 30% SUVmax and 40%SUVmax threshold) using 3D slicer software to extract 128 radiomic features from FDG-PET images of 100 HNSCC patients independently by three operators. We assessed the distributional properties of all features and considered 92 log-transformed features for subsequent analysis. For each paired comparison of a feature, we fitted a separate linear mixed effect model using the method (two levels; manual versus one semi-automatic method) as a fixed effect and the subject and the operator as the random effects. We estimated different statistics-the intraclass correlation coefficient agreement (aICC), limits of agreement (LoA), total deviation index (TDI), coverage probability (CP) and coefficient of individual agreement (CIA)-to evaluate the agreement between the manual and semi-automatic methods.Main results. Accounting for all statistics across 92 features, the JEI method consistently demonstrated acceptable agreement with the manual method, with median values of aICC = 0.86, TDI = 0.94, CP = 0.66, and CIA = 0.91.Significance. This study demonstrated that JEI method is a reliable semi-automatic method for tumor delineation on HNSCC PET images.

A systematic review and meta-analysis of predictive and prognostic models for outcome prediction using positron emission tomography radiomics in head and neck squamous cell carcinoma patients.

BACKGROUND: Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular levels. Therefore, PET radiomics-based prediction and prognostic models have the potentials to understand tumour heterogeneity and assist clinicians with diagnosis, prognosis and management of the disease. We conducted a systematic review of published modelling information to evaluate the usefulness of PET radiomics in the prediction and prognosis of HNSCC patients. METHODS: We searched bibliographic databases (MEDLINE, Embase, Web of Science) from 2010 to 2021 and considered 31 studies with pre-defined inclusion criteria. We followed the CHARMS checklist for data extraction and performed quality assessment using the PROBAST tool. We conducted a meta-analysis to estimate the accuracy of the prediction and prognostic models using the diagnostic odds ratio (DOR) and average C-statistic, respectively. RESULTS: Manual segmentation method followed by 40% of the maximum standardised uptake value (SUVmax ) thresholding is a commonly used approach. The area under the receiver operating curves of externally validated prediction models ranged between 0.60-0.87, 0.65-0.86 and 0.62-0.75 for overall survival, distant metastasis and recurrence, respectively. Most studies highlighted an overall high risk of bias (outcome definition, statistical methodologies and external validation of models) and high unclear concern in terms of applicability. The meta-analysis showed the estimated pooled DOR of 6.75 (95% CI: 4.45, 10.23) for prediction models and the C-statistic of 0.71 (95% CI: 0.67, 0.74) for prognostic models. CONCLUSIONS: Both prediction and prognostic models using clinical variables and PET radiomics demonstrated reliable accuracy for detecting adverse outcomes in HNSCC, suggesting the prospect of PET radiomics in clinical settings for diagnosis, prognosis and management of HNSCC patients. Future studies of prediction and prognostic models should emphasise the quality of reporting, external model validation, generalisability to real clinical scenarios and enhanced reproducibility of results.

Guidance on medical physics expert support for nuclear medicine.

The Ionising Radiation (Medical Exposure) Regulations require employers to appoint suitable medical physics experts (MPE) for nuclear medicine services, and they also define the areas where MPEs are required to provide advice and specify matters that they must contribute towards. Applications for employer licences under IR(ME)R require employers to specify the level of MPE support available and if this is provided by onsite MPEs or remotely. Assessment of these applications by the Administration of Radioactive Substances Advisory Committee (ARSAC) has highlighted variability in the levels of MPE support being provided for similar services across the UK. A working party including representatives from IPEM, ARSAC, BIR and BNMS was formed and has produced these recommendations on MPE support. Nuclear medicine services were divided into seven broad categories and MPE support for each category has been considered. However, some services that differ from the scenarios provided in this guidance may require different levels of MPE support. Positron emission tomography (PET)/CT and gamma camera imaging have been considered separately here, although it is recognised that both PET/CT and gamma cameras are often sited within the same department in many centres. The separation has been done for pragmatic purposes, as there are felt to be sufficient differences in the MPE role requirements. This guidance sets out recommendations for MPE support, and broader physics support, to run a safe nuclear medicine service and defines the responsibilities of these staff for a range of clinical nuclear medicine services. The recommendations on MPE support made are advice, but will assist employers in meeting regulatory requirements.

A comparative analysis: international variation in PET-CT service provision in oncology-an International Cancer Benchmarking Partnership study.

OBJECTIVE: To explore differences in position emission tomography-computed tomography (PET-CT) service provision internationally to further understand the impact variation may have upon cancer services. To identify areas of further exploration for researchers and policymakers to optimize PET-CT services and improve the quality of cancer services. DESIGN: Comparative analysis using data based on pre-defined PET-CT service metrics from PET-CT stakeholders across seven countries. This was further informed via document analysis of clinical indication guidance and expert consensus through round-table discussions of relevant PET-CT stakeholders. Descriptive comparative analyses were produced on use, capacity and indication guidance for PET-CT services between jurisdictions. SETTING: PET-CT services across 21 jurisdictions in seven countries (Australia, Denmark, Canada, Ireland, New Zealand, Norway and the UK). PARTICIPANTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULTS: PET-CT service provision has grown over the period 2006-2017, but scale of increase in capacity and demand is variable. Clinical indication guidance varied across countries, particularly for small-cell lung cancer staging and the specific acknowledgement of gastric cancer within oesophagogastric cancers. There is limited and inconsistent data capture, coding, accessibility and availability of PET-CT activity across countries studied. CONCLUSIONS: Variation in PET-CT scanner quantity, acquisition over time and guidance upon use exists internationally. There is a lack of routinely captured and accessible PET-CT data across the International Cancer Benchmarking Partnership countries due to inconsistent data definitions, data linkage issues, uncertain coverage of data and lack of specific coding. This is a barrier in improving the quality of PET-CT services globally. There needs to be greater, richer data capture of diagnostic and staging tools to facilitate learning of best practice and optimize cancer services.

Detectability of small objects in PET/computed tomography phantom images with Bayesian penalised likelihood reconstruction.

OBJECTIVES: This study investigated the subcentimetre lesion detection gains of a Bayesian penalised likelihood reconstruction (BPLR) (Q.Clear, GE Healthcare, Milwaukee, USA) in PET/computed tomography (CT) phantom images and compares observer performance with ordered subset expectation maximisation (OSEM) reconstruction images (VUE Point HD, GE Healthcare). METHODS: Images were presented to three blinded experienced observers to identify lesions and assign confidence ratings. Responses were analysed using jackknife alternative free receiver operator characteristic (JAFROC) software. Phantom lesions (active and nonactive) were constructed using putty. Seventy nonactive and 93 (F) active lesions, with diameters of 3, 5 or 7 mm were suspended in active backgrounds at varying contrast ratios (2:1-32:1) within an National Electrical Manufacturers Association 2012 phantom. PET/CT images were acquired with a GE Discovery 710 and reconstructed using both BPLR (penalisation coefficient 400) and high-definition attenuation corrected (HDAC) OSEM (2 iterations, 24 subsets). RESULTS: Small but significant (P = 0.009) visual detection gains were seen for active lesions with BPLR [weighted JAFROC figure of merit (wJAFROC FOM) = 0.77] over OSEM (FOM = 0.74). When split by subset, these improvements were significant for 5 mm and lesion to background ratio of 8:1. No significant (P = 0.514) differences were seen for the identification of nonactive lesions of any size (BPLR FOM = 0.74 and OSEM FOM = 0.73). CONCLUSIONS: Significant detection gains were demonstrated for small active lesions with BPLR over OSEM. Coupled with the significant increase in contrast-to-noise ratio, these results support the use of BPLR in the imaging of small active (≤7 mm) lesions but show no improvement with BPLR in the identification of true negative lesions.

Diastolic Ventricular Interaction in Heart Failure With Preserved Ejection Fraction.

Background Exercise-induced pulmonary hypertension is common in heart failure with preserved ejection fraction ( HF p EF ). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise. Methods and Results Contrast stress echocardiography was performed in 30 HF p EF patients, 17 hypertensive controls, and 17 normotensive controls (healthy). Cardiac volumes, and normalized radius of curvature ( NRC ) of the interventricular septum at end-diastole and end-systole, were measured at rest and peak-exercise, and compared between the groups. The septum was circular at rest in all 3 groups at end-diastole. At peak-exercise, end-systolic NRC increased to 1.47±0.05 ( P<0.001) in HF p EF patients, confirming development of pulmonary hypertension. End-diastolic NRC also increased to 1.54±0.07 ( P<0.001) in HF p EF patients, indicating septal flattening, and this correlated significantly with end-systolic NRC (ρ=0.51, P=0.007). In hypertensive controls and healthy controls, peak-exercise end-systolic NRC increased, but this was significantly less than observed in HF p EF patients ( HF p EF , P=0.02 versus hypertensive controls; P<0.001 versus healthy). There were also small, non-significant increases in end-diastolic NRC in both groups (hypertensive controls, +0.17±0.05, P=0.38; healthy, +0.06±0.03, P=0.93). In HF p EF patients, peak-exercise end-diastolic NRC also negatively correlated ( r=-0.40, P<0.05) with the change in left ventricular end-diastolic volume with exercise (ie, the Frank-Starling mechanism), and a trend was noted towards a negative correlation with change in stroke volume ( r=-0.36, P=0.08). Conclusions Exercise pulmonary hypertension causes substantial diastolic ventricular interaction on exercise in some patients with HF p EF , and this restriction to left ventricular filling by the right ventricle exacerbates the pre-existing impaired Frank-Starling response in these patients.

Randomized double-blind placebo-controlled trial of perhexiline in heart failure with preserved ejection fraction syndrome.

Recently heart failure with preserved ejection fraction (HFpEF) has emerged as a huge epidemic. Increasing evidence shows the role of energy deficiency in the pathophysiology of HFpEF. In the current study, we hypothesize that the use of metabolic modulator perhexiline would correct myocardial energy deficiency and improve exercise capacity and diastolic abnormalities in patients with this syndrome.

SeHCAT retention values as measured with a collimated and an uncollimated gamma camera: a method comparison study.

TauroH-23-(Se) selena-25-homocholic acid retention values are used in the diagnosis of bile acid malabsorption. The standard method for measuring values is with an uncollimated gamma camera, which can create some logistic difficulties, with other background sources of activity, which are irrelevant when a collimator is used, becoming significant. In this study we compare the retention values obtained with a collimated and an uncollimated gamma camera in phantoms and in 23 patients. Bland-Altman plots were created using the data, which showed a mean bias in retention of 0.10% in the phantom study and 0.55% in the patient study between methods. A Wilcoxon signed-rank test with the null hypothesis of zero median difference between uncollimated and collimated methods was not statistically significant to P values less than 0.05 in the patient and phantom studies. In the patient study, on using a fixed boundary of retention (10%) between positive and negative status, the status of one patient was changed from negative (12%) to positive (9%). We conclude that measurement of retention with a collimated gamma camera is similar but not identical to that of uncollimated values. The clinical significance of this shift is unclear, as the threshold of significance and the method of integrating this measure with other clinical factors into management remain unclear.

Improvement in DMSA imaging using adaptive noise reduction: an ROC analysis.

Dimercaptosuccinic acid imaging is the 'gold standard' for the detection of cortical defects and diagnosis of scarring of the kidneys. The Siemens planar processing package, which implements adaptive noise reduction using the Pixon algorithm, is designed to allow a reduction in image noise, enabling improved image quality and reduced acquisition time/injected activity. This study aimed to establish the level of improvement in image quality achievable using this algorithm. Images were acquired of a phantom simulating a single kidney with a range of defects of varying sizes, positions and contrasts. These images were processed using the Pixon processing software and shown to 12 observers (six experienced and six novices) who were asked to rate the images on a six-point scale depending on their confidence that a defect was present. The data were analysed using a receiver operating characteristic approach. Results showed that processed images significantly improved the performance of the experienced observers in terms of their sensitivity and specificity. Although novice observers showed significant increase in sensitivity when using the software, a significant decrease in specificity was also seen. This study concludes that the Pixon software can be used to improve the assessment of cortical defects in dimercaptosuccinic acid imaging by suitably trained observers.

The suitability of gamma camera coincidence systems for nitrogen 13-labeled ammonia myocardial perfusion imaging: a quantitative comparison with full-ring PET.

BACKGROUND: The aim of this study was to examine the quality of nitrogen 13-labeled ammonia (NH(3)) perfusion data from coincidence-capable gamma camera positron emission tomography (GC-PET) systems compared with that from full-ring positron emission tomography (FR-PET). METHODS AND RESULTS: The performance parameters of the GC-PET system were examined and found adequate for imaging at the activity levels used clinically. We studied 15 patients who underwent stress and rest N-13-labeled NH(3) perfusion imaging on FR-PET and GC-PET systems. Quantitative analysis of perfusion values showed that GC-PET uptake was significantly lower than FR-PET uptake in 67.6% of segments. Bland-Altman analysis showed that the mean difference between FR-PET and GC-PET values was from 5.3% to 5.9%. Stress FR-PET identified 49 segments as having impaired perfusion, 46 (93.9%) of which were also identified by GC-PET. Fifty-six additional segments were identified as abnormal by GC-PET. These findings indicated a general overestimation of defect size on GC-PET. Analysis of the degree of perfusion reduction also found that GC-PET tended to overestimate defect contrast. These findings are similar to those previously found by workers examining fluorine 18-fluorodeoxyglucose uptake by both techniques. CONCLUSIONS: Good concordance was shown between GC-PET and FR-PET systems for N-13-labeled NH(3) perfusion imaging, although further work is required to optimize the technique.