Radiation dose around a PET scanner installation: Comparison of Monte Carlo simulations,analytical calculations and experimental results

PurposeMonte Carlo study of radiation transmission around areas surrounding a PET room.MethodsAn extended population of patients administered with ¹⁸F-FDG for PET-CT investigations was studied, collecting air kerma rate and gamma ray spectra measurements at a reference distance. An MC model of the diagnostic room was developed, including the scanner and walls with variable material and thickness. MC simulations were carried out with the widely used code GEANT4.ResultsThe model was validated by comparing simulated radiation dose values and gamma ray spectra produced by a volumetric source with experimental measurements; ambient doses in the surrounding areas were assessed for different combinations of wall materials and shielding and compared with analytical calculations, based on the AAPM Report 108.In the range 1.5–3.0 times of the product between the linear attenuation coefficient and thickness of an absorber (μ x), it was observed that the effectiveness of different combinations of shielding is roughly equivalent. An extensive tabulation of results is given in the text.ConclusionsThe validation tests performed showed a satisfactory agreement between the simulated and expected results. The simulated dose rates incident on, and transmitted by the walls in our model of PET scanner room, are generally in good agreement with analytical estimates performed using the AAPM Publication No. 108 method. This provides an independent confirmation of AAPM's approach. Even in this specific field of application, GEANT4 proved to be a relevant and accurate tool for dosimetry estimates, shielding evaluation and for general radiation protection use.     

Characterization of prompt gamma-ray emission with respect to the Bragg peak for proton beam range verification: A Monte Carlo study

In this paper we report a Geant4 simulation study to investigate the characteristic prompt gamma (PG) emission in a water phantom for real-time monitoring of the Bragg peak (BP) during proton beam irradiation. The PG production, emission spatial correlation with the BP, and position preference for detection with respect to the BP have been quantified in different PG energy windows as a function of proton pencil-beam energy from 100 to 200 MeV. The PG response to small BP shifts was evaluated using a 2 cm-thick slab with different human body materials embedded in a water phantom. Our results show that the prominent characteristic PG emissions of 4.44, 5.21 and 6.13 MeV exhibit distinctive correlation with the dose deposition curve. The accuracy in BP position identification using these characteristic PG rays is highly consistent as the beam energy increases from 100 to 200 MeV. There exists a position preference for PG detection with respect to the BP position, which has a strong dependence on the proton beam energy and PG energies. It was also observed that a submillimeter shift of the BP position can be realized by using PG signals. These results indicate that the characteristic PG signal is sensitive and reliable for BP tracking. Although the maximization of the PG measurement associated with the BP is difficult, it can be optimized with energy and detection position preferences.     

Quantification and monitoring of PET/CT data in multicentre trials: The Swiss SAKK 56/07 trial experience

AimTo outline the importance of continuous monitoring of quantitative positron emission tomography (PET) data in multicentre trials to minimize quantitative bias in longitudinal intra-patient PET studies in light of the multicentre SAKK 56/07 experience in quantification and monitoring ¹⁸F-FDG PET/CT data.Patients and methodsWe collected 64 uniform phantom ¹⁸F-FDG PET acquisitions periodically at the enrolling centres (12 European institutions). A core-laboratory analysed them for standard uptake value (SUV) accuracy (desired 1.00 ± 10%) and acceptable image noise was defined by a coefficient of variation (COV) less than 15%. In total, 151 patients ¹⁸F-FDG PET acquisitions (baseline and follow-up) were also collected and analysed to verify longitudinal coherence of main acquisition/reconstruction parameters (DICOM tags verification) and patient preparation, in particular the uptake time (desired uptake time [UT] = 60 ± 10 min).ResultsUniform phantom PET acquisition satisfied the inclusion criteria in 58/64 (89%) examinations. All PET scanner exhibited comparable SUV quantification, but we found large dispersion in terms of noise, with COV ranging 3–15%. Only 1 phantom PET acquisition was out of range with COV = 21.5%. Patient data exhibited important variation in uptake time with UT = 65 ± 10 min (mean ± SD), with only 111/151 (74%) patients’ examinations satisfying inclusion criteria while 26% were out of range.ConclusionsRegular monitoring of PET data in multicentre trials is capital to ensure longitudinal intra-patient PET data consistence and minimize quantitative bias while it helps to spread the culture of quality in participating centre. Recent EARL (EANM Research Ltd) standardization and unification of procedures is a welcome step in this direction.     

Study of thermodynamic properties of symmetric and asymmetric electrolyte systems in mixture with neutral components: Monte Carlo simulation results and integral equation predictions

Monte Carlo simulation is conducted to obtain the structure, excess internal energy and Helmholtz energy for systems containing charged and neutral hard spheres of comparable concentrations. The results are compared with the thermodynamic properties predicted by solving Ornstein–Zernike equation with hypernetted chain (HNC) and mean spherical approximation (MSA) closures. The HNC approximation is found to well represent the simulation results for both structure and excess energy, while the excess energy of MSA deviates from the simulation results in the intermediate- and high-density range. A simple modification of MSA, referred to as KMSA, is proposed to accurately predict the excess internal and Helmholtz energy in the studied density range. KMSA is proved to capture the effects of neutral component, size and charge asymmetry, system temperature and dielectric constant of the background solvent, on the excess energy of electrolyte systems.     

Eutrophication,recovery and temperature in Lake Mjøsa: detecting trends with monitoring data and sediment records

1. How climate warming may interact with other pressures on aquatic ecosystems is an important issue for research and management. We combined lake monitoring data with a palaeolimnological study to explore the combined effects of eutrophication and subsequent oligotrophication with a long‐term temperature increase in epilimnetic waters. Our goals were (i) to evaluate how well sediment‐based reconstructions reflect the instrumental observations, (ii) to use the palaeo‐record to characterise a reference state for the lake and (iii) to explore whether data from the sediment record can aid in separating the effects of nutrient load and temperature in a large and deep lake. 2. Lake Mjøsa is a large and deep lake in south‐eastern Norway. Eutrophication symptoms peaked in the 1970s, which led to extensive measures to reduce the phosphorus load. A monitoring programme has run continuously from 1972. Monitoring has documented a marked decrease in phosphorus load and algal biomass and also revealed an increase in epilimnetic temperature and extended summer stratification. 3. Records of algal pigments and diatoms were extracted from sediment cores taken from 236 m depth. The pigment record documented dramatic changes in lake production consistent with the monitoring record. The diatom record reflected well the eutrophication history of the lake and also demonstrated that the assemblage of the recent recovery stage differs from that of the pre‐eutrophication period. 4. Ordination of diatom assemblages over time constrained by proxies for nutrient load and temperature indicated that the diatom assemblage correlated with both factors, which together accounted for 60% of the variation in diatom composition. No interaction was detected between these factors. The results suggest that the diatom assemblage has responded to varying nutrient loads as well as to changes in temperature and/or factors that correlate with temperature. 5. Reconstructions of algal biomass and total phosphorus content mirrored known changes through the monitoring period, although the absolute phosphorus estimates were too high relative to the instrumental record. The sediment record from Lake Mjøsa provides a baseline for lake production in terms of algal pigments and organic contents, and for the diatom assemblage composition in a pristine stage.     

In vivo monitoring of the therapeutic efficacy of a CXCR1/2 inhibitor with 18F-FDG PET/CT imaging in experimental head and neck carcinoma: A feasibility study

The chemokine receptors CXCR1/2 play a key role in the aggressiveness of several types of cancers including head and neck squamous cell carcinomas (HNSCCs). In HNSCCs, CXCR1/2 signaling promotes cell proliferation and angiogenesis leading to tumor growth and metastasis. The competitive inhibitor of CXCR1/2, C29, inhibits the growth of experimental HNSCCs in mice. However, a non-invasive tool to monitor treatment response is essential to implement the use of C29 in clinical practices. ¹⁸F-FDG PET/CT is a gold-standard tool for the staging and the post-therapy follow-up of HNSCCs patients. Our study aimed to perform the first in vivo monitoring of C29 efficacy by non-invasive ¹⁸F-FDG PET/CT imaging. Mice bearing experimental HNSCCs (CAL33) were injected with ¹⁸F-FDG (T0) and thereafter treated (n = 7 mice, 9 tumors, 50 mg/kg by gavage) or not (n = 7 mice, 10 tumors) with C29 for 4 consecutive days. Final ¹⁸F-FDG-tumor uptake was determined at day 4 (TF). The average relative change (TF-T0) in ¹⁸F-FDG tumor uptake was +25.85 ± 10.93 % in the control group vs ?5.72 ± 10.07 % in the C29-treated group (p < 0.01). These results were consistent with the decrease of the tumor burden and with the decrease of tumor proliferating Ki67+ cells. These results paved the way for the use of ¹⁸F-FDG to monitor tumor response following C29 treatment.     

Translation of a standardized manufacturing protocol for mesenchymal stromal cells: A systematic comparison of validation and manufacturing data

BackgroundMany data are available on expansion protocols for mesenchymal stromal cells (MSCs) for both experimental settings and manufacturing for clinical trials. However, there is a lack of information on translation of established protocols for Good Manufacturing Practice (GMP) from validation to manufacturing for clinical application. We present the validation and translation of a standardized pre-clinical protocol for isolation and expansion of MSCs for a clinical trial for reconstitution of alveolar bone.MethodsKey parameters of 22 large-scale expansions of MSCs from bone marrow (BM) for validation were compared with 11 expansions manufactured for the clinical trial “Jaw bone reconstruction using a combination of autologous mesenchymal stromal cells and biomaterial prior to dental implant placement (MAXILLO1)” aimed at reconstruction of alveolar bone.ResultsDespite variations of the starting material, the robust protocol led to stable performance characteristics of expanded MSCs. Manufacturing of the autologous advanced therapy medicinal product MAXILLO-1-MSC was possible, requiring 21 days for each product. Transport of BM aspirates and MSCs within 24 h was guaranteed. MSCs fulfilled quality criteria requested by the national competent authority. In one case, the delivered MSCs developed a mosaic in chromosomal finding, showing no abnormality in differentiation capacity, growth behavior or surface marker expression during long-term culture. The proportion of cells with the mosaic decreased in long-term culture and cells stopped growth after 38.4 population doublings.ConclusionsClinical use of freshly prepared MSCs, manufactured according to a standardized and validated protocol, is feasible for bone regeneration, even if there was a long local distance between manufacturing center and clinical site. Several parameters, such as colony forming units fibroblasts (CFU-F), percentage of CD34+ cells, cell count of mononuclear cells (MNCs) and white blood cells (WBCs), of the BM may serve as a predictive tool for the yield of MSCs and may help to avoid unnecessary costs for MSC manufacturing due to insufficient cell expansion rates.     

Non‐invasive monitoring of subclinical and clinical actinic keratosis of face and scalp under topical treatment with ingenol mebutate gel 150 mcg/g by means of reflectance confocal microscopy and optical coherence tomography: New perspectives and comparison of diagnostic techniques

Actinic keratosis (AK) corresponds to the earliest stage of in situ squamous cell carcinoma and arises on chronically sun‐exposed skin. Around the clinically evident AKs, the apparently healthy epidermis may contain different grades of atypia that can be detected by noninvasive imaging techniques such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). Subclinical actinic keratosis (sAK) has captured increasing interest as a potential target of field therapies. The aim of this study was to evaluate in vivo the changes in the field cancerization undergoing treatment with topical ingenol mebutate by combining RCM and OCT. Twenty patients with field cancerization of the face and scalp were treated with ingenol mebutate gel (150 mcg/g) for three consecutive days on an area of 25 cm² containing at least two AKs, two sAKs and two apparently healthy sites. About 120 lesions were evaluated through clinical investigation and clinical, dermoscopical, RCM and OCT images at day 0, 4, 14 and 56 based on the diagnostic criteria for AKs. Main pathological features improved in both AKs and sAKs, in particular the epidermal thickness measured by OCT and the epidermal atypia graded by RCM. Local skin reactions (LSR) arose predominantly in the lesional area compared with healthy skin. A complete clearance was detected in 58% for AKs, and in 55% and 72% for sAKs measured by RCM and OCT, respectively. Both OCT and RCM allow the morphological representation of field cancerization including subclinical lesions and provide complementary information. Ingenol mebutate is effective not only in clinically evident but also in sAKs. The differences in LSR highlight the potential selectivity of the treatment.      

Serum steroid profiling by isotopic dilution-liquid chromatography-mass spectrometry: comparison with current immunoassays and reference intervals in healthy adults

Background

The simultaneous, rapid and reliable measurement of a wide steroid panel is a powerful tool to unravel physiological and pathological hormone status. Clinical laboratories are currently dominated by high-throughput immunoassays, but these methods lack specificity due to cross-reactivity and matrix interferences. We developed and validated an isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the simultaneous measurement of cortisol, corticosterone, 11deoxycortisol, androstenedione, deoxycorticosterone (DOC), testosterone, 17OHprogesterone, dehydroepiandrosterone (DHEA) and progesterone in serum, and compared it to routine immunoassays employed in our laboratory. We also established adult reference intervals in 416 healthy subjects.

Methods

0.9 ml of serum were spiked with labelled internal standards (IS) and extracted on C18 cartridges. Eluate was injected into a two-dimensional LC-system, purified in a perfusion column and separated on a C8 column during a 21 min gradient run. Analytes were revealed by atmospheric pressure chemical ionization (APCI) followed by multiple reaction monitoring (MRM) analysis.

Results

Of the four immunoassays compared with the ID-LC-MS/MS method, only the results of ElecsysE170 for cortisol, testosterone in males and progesterone > 1 ng/ml were in agreement with ID-LC-MS/MS. ElecsysE170 for testosterone in females and progesterone < 1 ng/ml, Immulite2000 for androstenedione, DSL-9000 for DHEA and 17OHP Bridge for 17OHprogesterone, respectively, showed poor agreement. Reference intervals and steroid age and fertility related fluctuations were established.

Conclusion

Our ID-LC-MS/MS method proved to be reliable and sensitive in revealing steroid circulating concentrations in adults and in highlighting the limits of routine immunoassays at low concentrations.