Both programs allowed statistical differentiation between Parkinson's syndrome and essential tremor. Strict operator protocols are needed with QuantiSPECT to reduce inter- and intra-operator variation. The three-dimensional method (BRASS) gave greater concordance than the two-dimensional method (QuantiSPECT) with the visual assessment, but at a cost of increased operator time.
The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose–response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8–196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient’s activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities’ were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.
The limitations of traditional targeted radionuclide therapy (TRT) dosimetry can be overcome by using voxel-based techniques. All dosimetry techniques are reliant on a sequence of quantitative emission and transmission data. The use of (131)I, for example, with NaI or mIBG, presents additional quantification challenges beyond those encountered in low-energy NM diagnostic imaging, including dead-time correction and additional photon scatter and penetration in the camera head. The Royal Marsden Dosimetry Package (RMDP) offers a complete package for the accurate processing and analysis of raw emission and transmission patient data. Quantitative SPECT reconstruction is possible using either FBP or OS-EM algorithms. Manual, marker- or voxel-based registration can be used to register images from different modalities and the sequence of SPECT studies required for 3-D dosimetry calculations. The 3-D patient-specific dosimetry routines, using either a beta-kernel or voxel S-factor, are included. Phase-fitting each voxel's activity series enables more robust maps to be generated in the presence of imaging noise, such as is encountered during late, low-count scans or when there is significant redistribution within the VOI between scans. Error analysis can be applied to each generated dose-map. Patients receiving (131)I-mIBG, (131)I-NaI, and (186)Re-HEDP therapies have been analyzed using RMDP. A Monte-Carlo package, developed specifically to address the problems of (131)I quantification by including full photon interactions in a hexagonal-hole collimator and the gamma camera crystal, has been included in the dosimetry package. It is hoped that the addition of this code will lead to improved (131)I image quantification and will contribute towards more accurate 3-D dosimetry.
Background Bisphenol exposure is widespread and correlated with diabetes and cardiovascular disease. Previous intervention studies have successfully lowered bisphenol exposure among women of normal weight. The primary objective of this study was to develop and test the feasibility of a 3-week behavioral change intervention, rooted in social cognitive theory, to lower a broad range of bisphenols (BPA, BPS, and BPF) in women with obesity. Methods Thirty women with obesity (31.1 ± 5.6 kg/m2, 21.1 ± 3.1 years) were randomly assigned to an intervention or control. The intervention included weekly face-to-face meetings to reduce bisphenol exposures from food, cosmetics, and packaged products. Fasting urinary bisphenols, creatinine, and weight were assessed at study entry and after 3 weeks. Results The intervention was evaluated as feasible (100% of enrollment and recruitment, 96% of retention and attendance at lesson plan visits, and 96% of a collection of urine samples). Adherence to the intervention was estimated based on completion of self-monitoring records; the number of daily records completed was 7.7 ± 1.3 (mean ± SD) after week 1, 7.1 ± 1.5 after week 2, and 4.4 ± 0.9 after week 3. In secondary analysis, there was a significant treatment × time effect on creatinine-corrected urinary BPS (− 1.42 μg/g creatinine in the intervention vs. − 0.09 μg/g creatinine in the control group). Conclusion In women with obesity, the 3-week intervention was considered feasible with promising preliminary results of decreasing BPS concentrations. These data warrant future large-scale clinical trial interventions to reduce bisphenol exposure and determine whether reductions in bisphenols positively impact diabetes and cardiovascular disease risk markers. This study was retroactively registered at ClinicalTrial.gov Identifier NCT03440307.
Primary ciliary dyskinesia (PCD) is a genetic condition affecting one in 10 000-40 000 people from birth [1]; cilia fail to beat, and the airway clearance of mucus and debris is severely impaired. If untreated, this results in progressive lung infection leading to bronchiectasis and ultimately respiratory failure. Additionally, delayed diagnosis has implications for genetic counselling, appropriate management of glue ear and fertility advice. Early diagnosis and appropriate treatment are believed to improve outcome. The diagnosis of PCD is highly specialised and results can remain inconclusive, despite state of the art equipment and diagnostic techniques. A European consensus statement [2,3] highlighted that there is no ''gold-standard'' diagnostic test; diagnosis requires expert review of clinical history and screening tests (nasal nitric oxide measurement) alongside analysis of ciliary function and ultrastructure [2]. It is recommended that ciliary activity of respiratory epithelial cells obtained by nasal or bronchial brushing is recorded using a high-speed video camera mounted on a microscope. The images are played back in slow motion to analyse ciliary beat pattern (CBP) and frequency (CBF). Transmission electron microscopy (TEM) is used to assess ciliary ultrastructure [4]. Diagnostic uncertainty can be caused by secondary damage of the epithelium during sampling or due to infection or inflammation of epithelia; this damage can lead to abnormalities of ultrastructure, CBF and CBP. Furthermore, diagnosis is hindered by normal ciliary ultrastructure in 3-30% of cases of PCD [5,6]. To improve diagnostic certainty, a variety of further investigations can be employed [2], including reanalysis of CBF, CBP and TEM following culture of the cells at an air-liquid interface [7,8], or using immunofluorescence microscopy [9] to identify ciliary proteins. A single-centre study has previously reported the use of pulmonary radioaerosol mucociliary clearance (MCC) in the diagnosis of PCD [10]. The method is based on clearance patterns after the inhalation of a radioaerosol tracer. It provides a whole-lung functional test for pulmonary radioaerosol MCC. The investigation is noninvasive and has been used in thousands of patients with other lung diseases, as young as ,5 years. The authors reported that MCC was an effective noninvasive functional test for PCD [10] but the study was preliminary, and the feasibility of this complex technique and interpretation of data have not been assessed in other centres. We therefore conducted a study to replicate the results using a standardised protocol. This study was approved by the National Research Ethics Service (South Central committee 11/ SC/0192) and all subjects gave written informed consent.
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