Quantitative and clinical implications of the EARL2 versus EARL1 [18F]FDG PET-CT performance standards in head and neck squamous cell carcinoma.

BACKGROUND: The EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment. METHODS: Forty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale. RESULTS: There was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients. CONCLUSIONS: Using the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients.

Repeatability and Reproducibility Uncertainty in Magnetic Resonance-Based Electric Properties Tomography of a Homogeneous Phantom.

Uncertainty assessment is a fundamental step in quantitative magnetic resonance imaging because it makes comparable, in a strict metrological sense, the results of different scans, for example during a longitudinal study. Magnetic resonance-based electric properties tomography (EPT) is a quantitative imaging technique that retrieves, non-invasively, a map of the electric properties inside a human body. Although EPT has been used in some early clinical studies, a rigorous experimental assessment of the associated uncertainty has not yet been performed. This paper aims at evaluating the repeatability and reproducibility uncertainties in phase-based Helmholtz-EPT applied on homogeneous phantom data acquired with a clinical 3 T scanner. The law of propagation of uncertainty is used to evaluate the uncertainty in the estimated conductivity values starting from the uncertainty in the acquired scans, which is quantified through a robust James-Stein shrinkage estimator to deal with the dimensionality of the problem. Repeatable errors are detected in the estimated conductivity maps and are quantified for various values of the tunable parameters of the EPT implementation. The spatial dispersion of the estimated electric conductivity maps is found to be a good approximation of the reproducibility uncertainty, evaluated by changing the position of the phantom after each scan. The results underpin the use of the average conductivity (calculated by weighting the local conductivity values by their uncertainty and taking into account the spatial correlation) as an estimate of the conductivity of the homogeneous phantom.

Mesorectal shape variation in rectal cancer radiotherapy in prone position using a belly board.

BACKGROUND AND PURPOSE: In rectal cancer patients, radiotherapy in prone position using a belly board can reduce the dose to organs at risk. For this patient group we investigated inter-fraction shape variation of the mesorectal part of the clinical target volume (CTV) and determined planning target volume (PTV) margins. MATERIALS AND METHODS: Patients with rectal cancer receiving neoadjuvant (chemo)radiotherapy were eligible. For each patient a planning computed tomography (pCT) and five cone-beam CT (CBCT) scans were acquired in prone position using a belly board. The mesorectal CTV was delineated on all scans. Mesorectal shape variation was quantified relative to the pCT. PTV margins were derived locally and averaged for separate subregions of the mesorectal CTV. For each patient a total PTV was constructed using our clinical margins for mesorectal and lymph node CTVs. An artificial dose distribution conforming to this PTV was used to calculate the coverage for the mesorectal CTV using the CBCT delineations. RESULTS: In 19 rectal cancer patients the derived PTV margins were smallest in the upper-lateral region (6 mm) and largest in the upper-anterior region (16 mm). PTV margins for the upper-anterior region were larger for female patients (19 mm) compared to male patients (14 mm). Clinical margins for the total PTV were sufficient for a coverage of at least 97% of the mesorectal CTV for all patients. CONCLUSIONS: Mesorectal shape variation is heterogeneous and largest in the upper-anterior region, in rectal cancer patients irradiated in prone position and using a belly board.

Reply to "Comment on Liu et al. 'Discrepancies of Measured SAR between Traditional and Fast Measuring Systems' Int. J. Environ. Res. Public Health, 2020, 17, 2111".

The authors of this reply published an article in International Journal of Environmental Research and Public Health and received comments from Douglas and Kuster. Responses are made to these comments with complementary explanations and numerical results.

Discrepancies of Measured SAR between Traditional and Fast Measuring Systems.

Human exposure to mobile devices is traditionally measured by a system in which the human body (or head) is modelled by a phantom and the energy absorbed from the device is estimated based on the electric fields measured with a single probe. Such a system suffers from low efficiency due to repeated volumetric scanning within the phantom needed to capture the absorbed energy throughout the volume. To speed up the measurement, fast SAR (specific absorption rate) measuring systems have been developed. However, discrepancies of measured results are observed between traditional and fast measuring systems. In this paper, the discrepancies in terms of post-processing procedures after the measurement of electric field (or its amplitude) are investigated. Here, the concerned fast measuring system estimates SAR based on the reconstructed field of the region of interest while the amplitude and phase of the electric field are measured on a single plane with a probe array. The numerical results presented indicate that the fast SAR measuring system has the potential to yield more accurate estimations than the traditional system, but no conclusion can be made on which kind of system is superior without knowledge of the field-reconstruction algorithms and the emitting source.

EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations.

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time-activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.

Uncertainty Analysis in the Calibration of an Emission Tomography System for Quantitative Imaging.

It is generally acknowledged that calibration of the imaging system (be it a SPECT or a PET scanner) is one of the critical components associated with in vivo activity quantification in nuclear medicine. The system calibration is generally performed through the acquisition of a source with a known amount of radioactivity. The decay-corrected calibration factor is the "output" quantity in a measurement model for the process. This quantity is a function of a number of "input" variables, including total counts in the volume of interest (VOI), radionuclide activity concentration, source volume, acquisition duration, radionuclide half-life, and calibration time of the radionuclide. Uncertainties in the input variables propagate through the calculation to the "combined" uncertainty in the output quantity. In the present study, using the general formula given in the GUM (Guide to the Expression of Uncertainty in Measurement) for aggregating uncertainty components, we derive a practical relation to assess the combined standard uncertainty for the calibration factor of an emission tomography system. At a time of increasing need for accuracy in quantification studies, the proposed approach has the potential to be easily implemented in clinical practice.

Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis.

BACKGROUND: To report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions. METHODS: Newly diagnosed patients, aged 3-21, with standard-risk (SR) or high-risk (HR) medulloblastoma were eligible. A dose of 23.4 or 36.0 Gy in daily fractions of 1.8 Gy was prescribed to the craniospinal axis, followed by a boost to the primary tumor bed (54 or 55.8 Gy) and metastases (39.6-55.8 Gy), when indicated. Weekly, an intravenous bolus of vincristine was combined for patients with SR medulloblastoma and patients participating in the COG-ACNS-0332 study. Common toxicity criteria (CTC, version 2.0) focusing on skin, alopecia, voice changes, conjunctivitis, anorexia, dysphagia, gastro-intestinal symptoms, headache, fatigue and hematological changes were scored weekly during radiotherapy. RESULTS: From 2010 to 2014, data from 15 consecutive patients (SR, n = 7; HR, n = 8) were collected. Within 72 h from onset of treatment, vomiting (66 %) and headache (46 %) occurred. During week 3 of treatment, a peak incidence in constipation (33 %) and abdominal pain/cramping (40 %) was observed, but only in the subgroup of patients (n = 9) receiving vincristine (constipation: 56 vs 0 %, P = .04; pain/cramping: 67 vs 0 %, P = .03). At week 6, 73 % of the patients developed faint erythema of the cranial skin with dry desquamation (40 %) or moist desquamation confined to the skin folds of the auricle (33 %). No reaction of the skin overlying the spinal target volume was observed. CONCLUSIONS: Headache at onset and gastro-intestinal toxicity, especially in patients receiving weekly vincristine, were the major complaints of patients with medulloblastoma undergoing craniospinal irradiation with IMRT.

Uncertainty propagation for SPECT/CT-based renal dosimetry in (177)Lu peptide receptor radionuclide therapy.

A computer model of a patient-specific clinical (177)Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of (177)Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.

Assessing the performance of standard methods to predict the standard uncertainty of air quality data having incomplete time coverage.

As a result of the complex nature of operating multi-station national air quality networks it is rare that complete data sets are produced from these networks. The reliance of most air quality legislation on the assessment of measured annual average concentrations against target or limit concentrations necessitates the use of methods to calculate an annual average value and the uncertainty in this value in the absence of a complete data set for the year in question. Standard procedures exist for performing these calculations, but it is not clear how effective these are when data having low time resolution are collected and missing data accounts for large periods of the year. This paper investigates the influence of these deficiencies using data from UK air quality networks in the form of monthly average concentrations for polycyclic aromatic hydrocarbons and for metals in the PM10 phase of ambient air. Whilst the standard methods currently employed produce good results on average, for individual cases the uncertainty in the annual average calculated when data is missing may be appreciably different from that obtained when full knowledge of the distribution of the data is known. These effects become more apparent as the quantity of missing data increases.

Improved strategies for calculating annual averages of ambient air pollutants in cases of incomplete data coverage.

The consequences of missing data during air quality monitoring activities and the calculation of the annual average mass concentration of ambient pollutants are discussed. Possible strategies for mitigating totally and partially missing data during given measurement periods are presented and evaluated. A mathematical description of a preferred method for the determination of annual average concentration using the simple mean, and not using time weighting to account for missing data, is justified. It is hoped this discussion paper will provoke debate in the air quality community about the best way to assess measured concentrations of ambient pollutants against legislative values.

The use of a Monte Carlo method for uncertainty calculation, with an application to the measurement of neutron ambient dose equivalent rate.

This paper is concerned with the use of a Monte Carlo method for uncertainty calculation as an implementation of the propagation of distributions. It reviews the basic principles of the propagation of distributions and numerical aspects of a Monte Carlo implementation. It also discusses the possible advantages in some circumstances of the propagation of distributions over the GUM uncertainty framework, and how the results obtained in any particular instance can be compared with those provided by that framework. To illustrate these various aspects, an application to the measurement of neutron dose equivalent rate is given. A key consideration in this application is the manner in which the dominant source of uncertainty, namely that associated with the field-specific correction factor, is treated. The information available concerning this factor constitutes the correction factors for a set of fields of the same type as that in which a measurement is being made. This information is encoded as a probability density function (PDF) for the correction factor. This PDF constitutes an input to both methods of evaluation.

Harmonisation of coupled calibration curves to reduce correlated effects in the analysis of natural gas by gas chromatography.

Quantitative analysis of natural gas depends on the calibration of a gas chromatograph with certified gas mixtures and the determination of a response relationship for each species by regression analysis. The uncertainty in this calibration is dominated by variations in the amount of the sample used for each analysis that are strongly correlated for all species measured in the same run. The "harmonisation" method described here minimises the influence of these correlations on the calculated calibration curves and leads to a reduction in the root-mean-square residual deviations from the fitted curve of a factor between 2 and 5. Consequently, it removes the requirement for each run in the calibration procedure to be carried out under the same external conditions, and opens the possibility that new data, measured under different environmental or instrumental conditions, can be appended to an existing calibration database.