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Advances of radiation delivery devices have increased the complexity of the radiation oncology treatments. Herewith, outcome of the treatment, as well as patient safety, strongly depend on the consistency of absorbed dose delivery. Both can be ensured by comprehensive system of verification of calculated absorbed dose distributions. Standard method is evaluation of calculated absorbed dose distribution according to gamma method, using a 2-D detector and a homogeneous phantom, to obtain measured dose distribution. Purpose of this research was to investigate the influence of tolerance criteria on gamma passing rate. Additionally, the agreement in heterogeneous phantom was analysed. Absorbed dose calculations were performed using systems Monaco and XiO. Detector with 1020 ionization chambers in homogeneous phantom and semi-anthropomorphic phantom was used for measurements. Absorbed dose distributions of around 3500 patients were analysed using gamma method. In homogeneous phantom, average gamma passing rates were within tolerance for 3 %/2 mm. For measurements in heterogeneous media, the highest average gamma passing rate was obtained for small volumes of medium treatment complexity (γ¯=93.84%), while large volumes of treatment with low complexity yielded the lowest gamma passing rates (γ¯= 83.22%).

Advanced, Monte Carlo (MC) based dose calculation algorithms, determine absorbed dose as dose to medium-in-medium (Dm,m) or dose to water-in-medium (Dw,m). Some earlier studies identified the differences in the absorbed doses related to the calculation mode, especially in the bone density equivalent (BDE) media. Since the calculation algorithms built in the treatment planning systems (TPS) should be dosimetrically verified before their use, we analyzed dose differences between two calculation modes for the Elekta Monaco TPS. We compared them with experimentally determined values, aiming to define a supplement to the existing TPS verification methodology.

Dose assessment of diagnostic nuclear medicine procedures is necessary to further optimize respective procedure, estimate radiation risk, improve radiation safety and verify compliance of local practice with guidelines. In line with Council Directive 2013/59/EURATOM, patient medical documentation should include information related to radiation exposure. The aim of this work is to present the patient radiation dose assessment system designed for routine clinical use, that uses in-house designed worksheets for dose calculation based on relevant parameters introduced by the ICRP publications. Dose reports provide information about the absorbed dose delivered to the target and non-target organs of interest and the effective dose for each diagnostic procedure. The data from the dose reports was used to investigate average patient exposure levels during a one-year period and the results are presented. The implemented system has improved the quality of services provided and understanding of radiation risks. Moreover, the presented results have stimulated further optimization of nuclear medicine processes.

Majority of health institutions in Croatia do not have medical physicists in diagnostic radiology. Regarding this, in the west region of Croatia collaboration between public health institution and University Hospital Rijeka was initiated in 2015. Quality Assurance program was implemented in these public health institutions during 2015 and 2016 and the next step was to assess patient doses for the most frequent X-ray examinations. This included five public health institutions: 1 university hospital, 1 general hospital, 1 special hospital, 2 public health institutions with 13 facilities. The aim of this study was to carry out assessment of patient doses and to establish local diagnostic reference levels of entrance surface air kerma for every institution for six most frequent X-ray examinations. Also, local diagnostic reference levels for the whole west region of Croatia were established and compared with the national diagnostic reference levels and latest published data. Median entrance surface air kerma values for thorax PA, thorax LAT, cervical spine AP, thoracic spine AP, lumbar spine AP, pelvis AP and sinuses are 0.14 mGy, 0.50 mGy, 0.52 mGy, 1.50 mGy, 2.52 mGy, 2.03 mGy, and 1.03 mGy, respectively. Diagnostic reference levels proposed for our region were comparable with other studies.

The accuracy of dose calculation is crucial for success of the radiotherapy treatment. One of the methods that represent the current standard for patient-specific dosimetry is the evaluation of dose distributions measured with an ionization chamber array inside a homogeneous phantom using gamma method. Nevertheless, this method does not replicate the realistic conditions present when a patient is undergoing therapy. Therefore, to more accurately evaluate the treatment planning system (TPS) capabilities, gamma passing rates were examined for beams of different complexity passing through inhomogeneous phantoms.

The computed tomography has become a standard tool in radiation therapy treatment planning. Additionally, there is a growing awareness of the dose delivered to the part of the body outside the target volume. The ionizing radiation carries a stochastic risk of malignancy, therefore, the doses should be kept as low as reasonably achievable in order to provide an adequate information needed for the radiotherapy planning. The objective of this work was to set up the initial diagnostic reference levels and correlate to the image quality that would be used in the future optimization of localization scans. To quantify the doses from computed tomography localization scans at the University Hospital Rijeka, local diagnostic reference levels were established for five most common procedures of different anatomical regions; head, head and neck, pelvis, breast and thorax. The Computed Tomography Dose Index volumetric and the Dose-Length Product were used as dose indicators and scanning parameters were also recorded. The image quality assessment was performed for each set of images. The results were compared to the seldom published data in order to compare the clinical practice. The image quality for almost all of the body regions are scored as acceptable in average but require improvement. It is shown that the optimization of radiotherapy protocols is required. Therefore, these results will be used as a guideline for that process. The establishment of the national diagnostic reference levels for computed tomography localization procedures in radiation therapy is the next step and is currently an ongoing process.

The measurement of neutron dose equivalent was made in four dual energy linear accelerator rooms. Two of the rooms were reconstructed after decommissioning of 60Co units, so the main limitation was the space. The measurements were performed by a nuclear track etched detectors LR-115 associated with the converter (radiator) that consist of 10B and with the active neutron detector Thermo BIOREM FHT 742. The detectors were set at several locations to evaluate the neutron ambient dose equivalent and/or neutron dose rate to which medical personnel could be exposed. Also, the neutron dose dependence on collimator aperture was analyzed. The obtained neutron dose rates outside the accelerator rooms were several times smaller than the neutron dose rates inside the accelerator rooms. Nevertheless, the measured neutron dose equivalent was not negligible from the aspect of the personal dosimetry with almost 2 mSv a year per person in the areas occupied by staff (conservative estimation). In rooms with 15 MV accelerators, the neutron exposure to the personnel was significantly lower than in the rooms having 18 MV accelerators installed. It was even more pronounced in the room reconstructed after the 60Co decommissioning. This study confirms that shielding from the neutron radiation should be considered when building vaults for high energy linear accelerators, especially when the space constraints exist.

DNA from archival Papanicolaou stained smears was successfully amplified using the polymerase chain reaction (PCR) to see if it could be used for retrospective genome studies such as detection of the presence of human papilloma virus (HPV) and changes in p53 gene expression. DNA was isolated and purified by treatment with proteinase K, phenol/chloroform, and isoamyl alcohol. Segments of the human beta actin and TGF beta 1 gene were amplified by PCR. Of all stains used in the preparation of Papanicolaou smears, only eosin was detectable as a greenish band in ethidium bromide treated DNA gels under ultraviolet illumination. [ABSTRACT FROM PUBLISHER]

Purpose: The aim of this study was to evaluate the performance of myocardial perfusion imaging (MPI) systems in detecting perfusion defects (PDs). The defect perfusion index (DPI) was introduced to extend and further advance the current MPI quality metrics., Methods: An anthropomorphic phantom simulating normal and pathological myocardial perfusion conditions was imaged by various NaI-crystal detector systems with and without corrections for scatter (SC) and attenuation (AC) (Symbia, Symbia + SC, Symbia IQ + SCAC, Symbia IQ), and cadmium-zinc-telluride detector systems without corrections (DSPECT, D530c). The extent of PD and the summed score (SS) were obtained by comparing polar maps with ad hoc normal databases created for each MPI system by using phantom polar maps with normal perfusion. The segmental uptake (SU) and the global uniformity (GU) were evaluated. The DPI was calculated on segments included in the PD to minimize attenuation artifacts outside the PD. The 17 segmental model was used., Results: The highest level of uniformity of polar map was obtained for Symbia IQ + SCAC. D530c showed the highest extent of PD and dependence of the extent on the PD position. It showed in general the lowest SU values and the highest GU due to attenuation artifacts. Nevertheless, D530c outperforms other MPI systems in terms of PD detection, showing the highest DPI value. DSPECT system showed the lowest SS value, and DPI values comparable to NaI-crystal detector systems., Conclusion: The DPI can be evaluated to investigate the intrinsic ability of MPI systems to detect PDs, whatever the quantitative post-processing software used., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective . In this multicentric collaborative study, we aimed to verify whether the selected radiation detectors satisfy the requirements of TRS-483 Code of Practice for relative small field dosimetry in megavoltage photon beams used in radiotherapy, by investigating four dosimetric characteristics. Furthermore, we intended to analyze and complement the recommendations given in TRS-483. Approach . Short-term stability, dose linearity, dose-rate dependence, and leakage were determined for 17 models of detectors considered suitable for small field dosimetry. Altogether, 47 detectors were used in this study across ten institutions. Photon beams with 6 and 10 MV, with and without flattening filters, generated by Elekta Versa HD TM or Varian TrueBeam TM linear accelerators, were used. Main results . The tolerance level of 0.1% for stability was fulfilled by 70% of the data points. For the determination of dose linearity, two methods were considered. Results from the use of a stricter method show that the guideline of 0.1% for dose linearity is not attainable for most of the detectors used in the study. Following the second approach (squared Pearson's correlation coefficient r 2 ), it was found that 100% of the data fulfill the criteria r 2 > 0.999 (0.1% guideline for tolerance). Less than 50% of all data points satisfied the published tolerance of 0.1% for dose-rate dependence. Almost all data points (98.2%) satisfied the 0.1% criterion for leakage. Significance . For short-term stability (repeatability), it was found that the 0.1% guideline could not be met. Therefore, a less rigorous criterion of 0.25% is proposed. For dose linearity, our recommendation is to adopt a simple and clear methodology and to define an achievable tolerance based on the experimental data. For dose-rate dependence, a realistic criterion of 1% is proposed instead of the present 0.1%. Agreement was found with published guidelines for background signal (leakage)., (Creative Commons Attribution license.)

Purpose: The purpose of this study is to calculate volume averaging correction factors for detectors used in the dosimetry of Gamma Knife's narrow photon beams, and to determine the impact of volume averaging on the field output correction factor., Methods: Simulations of different Gamma Knife fields were done using elliptical dose model formalism with newly introduced fit functions. To determine volume averaging correction factors a calculation of the absorbed dose over the volume of the detector was performed. The elliptical dose model was tested with respect to absorbed dose distribution for different volumes and compared with the calculations of Leksell GammaPlan v.11.3.1., Results: The largest differences in absorbed dose calculated by the elliptical model and Leksell GammaPlan are 2.25%, 1.5%, and 0.6% for 16, 8, and 4 mm field sizes, respectively. Volume averaging correction factors were determined for six ionization chambers, five semiconductor detectors, a diamond, and two plastic scintillator detectors. In general, for all examined detectors the impact of volume averaging is more pronounced for smaller field sizes. All studied ionization chambers had a larger volume than other detectors, therefore the volume averaging correction factors for ionization chambers are larger for all investigated field sizes. Besides the fact that plastic scintillator detectors can be considered tissue-equivalent, volume averaging correction factor should be applied., Conclusion: Volume averaging correction factors for different detectors are determined and suitable detectors for dosimetry of Gamma Knife's narrow photon beams are recommended. It is shown that volume averaging has a dominant contribution to a field output correction factor., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Single photon emission computed tomography (SPECT) procedures are characterized by long acquisition time to acquire diagnostically acceptable image data. The goal of this investigation was to assess the feasibility of using a deep convolutional neural network (DCNN) to reduce the acquisition time. The DCNN was implemented using the PyTorch and trained using image data from standard SPECT quality phantoms. The under-sampled image dataset is provided to neural network as input, while missing projections were provided as targets. The network is to produce for the output the missing projections. The baseline method of calculating the missing projections as arithmetic means of adjacent ones was introduced. The obtained synthesized projections and reconstructed images were compared to original data and baseline data across several parameters using PyTorch and PyTorch Image Quality code libraries. Results obtained from comparisons of projection and reconstructed image data show the DCNN clearly outperforming the baseline method. However, subsequent analysis revealed the synthesized image data being more comparable to under-sampled than to fully-sampled image data. The results of this investigation imply that neural network can replicate coarser objects better. However, densely sampled clinical image datasets, coarse reconstruction matrices and patient data featuring coarse structures combined with a lack of baseline data generation methods will hamper the ability to analyse the neural network outputs correctly. This study calls for use of phantom image data and introduction of a baseline method in the evaluation of neural network outputs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Virtual monoenergetic (VM) dual-energy computed tomography (DE-CT) enables grey-to-white matter contrast-to-noise ratio optimization, potentially increasing ischaemic brain oedema visibility. The aim of this study was to compare the diagnostic accuracy of VM and standard DE-CT reconstructions for early stroke detection., Methods: Consecutive patients with non-contrast DE-CT of the brain scanned within 12 h of stroke symptom onset were prospectively included in the study. Patients with other significant brain pathology were excluded. Two radiologists jointly evaluated standard and VM reconstructions (from 40 to 190 keV at increments of 10 keV) for early stroke signs on a four-point Likert scale: (a) stroke definitely present, (b) stroke probably present, (c) probably no stroke, and (d) definitely no stroke. Follow-up imaging and clinical data served as the standard of reference. Diagnostic accuracy was evaluated by receiver operating characteristic analysis., Results: Stroke incidence among 184 patients was 76%. In 64 patients follow-up imaging served as the standard of reference: ischemic brain oedema detection was significantly more accurate on VM reconstructions at 80 keV compared with standard DE-CT reconstructions (area under the curve (AUC) = 0.821 vs . AUC = 0.672, p  = 0.002). The difference was most prominent within the first 3 h after symptom onset (at 11%, AUC = 0.819 vs . AUC = 0.709, p  = 0.17) and in patients with National Institutes of Health Stroke Scale above 16 (at 37.5%, AUC = 1 vs . AUC = 0.625, p  = 0.14)., Conclusion: VM DE-CT reconstructions at 80 keV appear to be the optimal non-contrast CT technique for diagnosing early ischaemic stroke, particularly within the first 3 h after symptom onset and in severely ill patients.

Objective: To present results of the first national survey on reference levels of CT imaging performed for the treatment planning purposes in radiation oncology in Croatia., Methods: Data for CT protocols of five anatomical regions including head, head and neck, pelvis, breast, and thorax were collected at eight radiation oncology departments in Croatia. Data included volume CT dose index (CTDI vol ), dose-length product (DLP), scan length and set of acquisition and reconstruction parameters. Data on a total of 600 patients were collected. Median values of scan length, DLP and CTDI vol were calculated for each acquisition protocol. Third quartiles of the median CTDI vol and DLP values were proposed as the national radiotherapy planning reference levels (RPRL)., Results: The largest CoV were assessed for RT Breast (63.8% for CTDI vol ), RT Thorax (79.7% for DLP) and RT H&N (21.2% for scan length). RT Head had the lowest CoV for CTDI vol (1,9%) and DLP (17,2%), while RT Breast had the lowest coefficient of variation for scan length (12.8%). Proposed national RPRLs are: for RT Head CTDI vol16cm  = 62 mGy and DLP 16cm  = 1738 mGy.cm; for RT H&N CTDI vol16cm  = 35 mGy and DLP 16cm  = 1444 mGy.cm; for RT Breast CTDI vol32cm  = 16 mGy and DLP 32cm  = 731 mGy.cm; for RT Thorax CTDI vol32cm  = 17 mGy and DLP 32cm  = 865 mGy.cm; for RT Pelvis CTDI vol32cm  = 20 mGy and DLP 32cm  = 1133 mGy.cm., Conclusions: Results of this study show variations in CT imaging for treatment planning practice at the national level which call for optimization of procedures., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Study determines differences in calculated dose distributions for non-small cell lung carcinoma (NSC LC) patients. NSC LC cases were investigated, being the most common lung cancer treated by radiotherapy in our clinical practice., Materials and Methods: A retrospective study of 15 NSCLC patient dose distributions originally calculated using standard superposition (SS) and recalculated using collapsed cone (CC ) and Monte Carlo (MC) based algorithm expressed as dose to medium in medium (MCD m ) and dose to water in medium (MCD w, ) was performed so that prescribed dose covers at least 99% of the gross target volume (GTV). Statistical analysis was performed for differences of conformity index (CI), heterogeneity index (HI), gradient index (GI), dose delivered to 2% of the volume (D 2% ), mean dose (D mean ) and percentage of volumes covered by prescribed dose (V 70Gy ). For organs at risk (OARs), D mean and percentage of volume receiving 20 Gy and 5Gy (V 20Gy , V 5Gy ) were analysed., Results: Statistically significant difference for GTVs was observed between MCD w and SS algorithm in mean dose only. For planning target volumes (PTVs), statistically significant differences were observed in prescribed dose coverage for CC, MCD m and MCD w . The differences in mean CI value for the CC algorithm and mean HI value for MCD m and MCD w were statistically significant. There is a statistically significant difference in the number of MUs for MCD m and MCD w compared to SS., Conclusion: All investigated algorithms succeed in managing the restrictive conditions of the clinical goals. This study shows the drawbacks of the CC algorithm compared to other algorithms used., Competing Interests: Conflict of interest No conflict of interest., (© 2022 Greater Poland Cancer Centre.)

Purpose: In order to introduce the concept of diagnostic reference levels (DRLs) in the national nuclear medicine practice a survey was proposed and completed through all nuclear medicine departments in Croatia. An additional aim was to increase the awareness of importance and full implementation of a comprehensive quality program that includes devices used in the nuclear medicine chain., Methods: Data were collected for more than 30 nuclear medicine single photon emission procedures. National DRLs (NDRLs) as administered activity and also as administered activity per unit mass were calculated in accordance to International Commission on Radiological Protection (ICRP) recommendations. Additionally, effective doses were estimated using conversion factors published by the ICRP., Results: NDRLs for nuclear medicine single photon emission procedures were proposed. For procedures performed in only one department typical values were presented as reference. Effective doses related to applied radiopharmaceuticals were calculated to estimate radiation risk related to respective nuclear medicine procedure in more detail., Conclusion: This work presents results of the first national survey on DRLs of nuclear medicine single photon emission procedures and proposes reliable NDRLs that represent an actual status of nuclear medicine practice in Croatia. Results have motivated departments to introduce and set their own typical values to be used, as one of the tools, for further optimization process. One of the drawbacks of the DRL concept in nuclear medicine is the lack of the image quality parameters involved. For this reason, a quantity that considers both radiation protection and image quality should be introduced., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess image quality and radiation dose associated with ultra-low dose CT protocol for patients with benign paranasal sinus diseases undergoing functional endoscopic surgery (FESS)., Methods: We scanned the head portion of Alderson RANDO phantom on a second generation, dual-source, multidetector-row CT scanner (Siemens Definition Flash) using standard-dose and five low-dose protocols. Two radiologists assessed the image quality for each protocol to determine best ultra-low-dose protocols for imaging patients with benign paranasal sinus diseases undergoing FESS. The ultra-low-dose CT protocols were then used for scanning. Thereafter, 40 adult patients (age range 18-54 years, M:F 23:17) were scanned with the four low dose scanning protocols (10 patients per protocol). On both transverse and coronal reformatted CT images, two radiologists assessed visibility of key anatomic landmarks for FESS on a 2-point scale (1 = clear and complete visualization; 2 = suboptimal visualization). Data were analyzed with descriptive statistics and Cohen's kappa coefficient for interobserver agreement., Results: In phantom study, the lowest dose scan protocol (CTDI vol 2.1 mGy, 70 kV, 75 mAs) was unacceptable due to poor image quality. For patient studies, both radiologists gave acceptable image quality scores for ultra-low-dose scan protocol with axial scan mode, automatic tube potential selection and tube current modulation (CTDI vol 2.2 mGy; DLP 22.9 mGy.cm) with up to 60% lower dose compared to prior standard-dose CT (CTDI vol 5.3 mGy; DLP 73.5 mGy.cm)., Conclusions: Ultra-low-dose CT protocol provides sufficient image quality for scanning patients undergoing functional endoscopic surgery for benign paranasal sinus diseases., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: The goal of the present work was to provide a large set of detector-specific output correction factors for seven small volume ionization chambers on two linear accelerators in four megavoltage photon beams utilizing perpendicular and parallel orientation of ionization chambers in the beam for nominal field sizes ranging from 0.5 cm 2  × 0.5 cm 2 to 10 cm 2  × 10 cm 2 . The present study is the second part of an extensive research conducted by our group., Methods: Output correction factors k Q clin , Q ref f clin , f ref were experimentally determined on two linacs, Elekta Versa HD and Varian TrueBeam for 6 and 10 MV beams with and without flattening filter for nine square fields ranging from 0.5 cm 2  × 0.5 cm 2 to 10 cm 2  × 10 cm 2 , for seven mini and micro ionization chambers, IBA CC04, IBA Razor, PTW 31016 3D PinPoint, PTW 31021 3D Semiflex, PTW 31022 3D PinPoint, PTW 31023 PinPoint, and SI Exradin A16. An Exradin W1 plastic scintillator and EBT3 radiochromic films were used as the reference detectors., Results: For all ionization chambers, values of output correction factors k Q clin , Q ref f clin , f ref were lower for parallel orientation compared to those obtained in the perpendicular orientation. Five ionization chambers from our study set, IBA Razor, PTW 31016 3D PinPoint, PTW 31022 3D PinPoint, PTW 31023 PinPoint, and SI Exradin A16, fulfill the requirement recommended in the TRS-483 Code of Practice, that is, 0.95 < k Q clin , Q ref f clin , f ref < 1.05 , down to the field size 0.8 cm 2  × 0.8 cm 2 , when they are positioned in parallel orientation; two of the ionization chambers, IBA Razor and PTW 31023 PinPoint, satisfy this condition down to the field size of 0.5 cm 2  × 0.5 cm 2 ., Conclusions: The present paper provides experimental results of detector-specific output correction factors for seven small volume ionization chambers. Output correction factors were determined in 6 and 10 MV photon beams with and without flattening filter down to the square field size of 0.5 cm 2  × 0.5 cm 2 for two orientations of ionization chambers - perpendicular and parallel. Our main finding is that output correction factors are smaller if they are determined in a parallel orientation compared to those obtained in a perpendicular orientation for all ionization chambers regardless of the photon beam energy, filtration, or linear accelerator being used. Based on our findings, we recommend using ionization chambers in parallel orientation, to minimize corrections in the experimental determination of field output factors. Latter holds even for field sizes below 1.0 cm 2  × 1.0 cm 2 , whenever necessary corrections remain within 5%, which was the case for several ionization chambers from our set. TRS-483 recommended perpendicular orientation of ionization chambers for the determination of field output factors. The present study presents results for both perpendicular and parallel orientation of ionization chambers. When validated by other researchers, the present results for parallel orientation can be considered as a complementary dataset to those given in TRS-483., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The evaluation of the performance of nine physiotherapy ultrasound transducers used clinically was performed in the hospital environment using an acoustically absorbing thermocromic tile developed at the National Physical Laboratory (UK). The method consists of exposing an acoustic absorber tile, part of which contains a thermochromic pigment, to the ultrasonic beam, thereby forming an image of the intensity profile of the transducer. Images acquired using thermochromic materials were postprocessed in order to estimate effective radiating area (ERA) and beam nonuniformity ratio (BNR) for ultrasound transducers operating within the frequency range from 1.0 to 3.3 MHz, and nominal applied intensities in the range of 1-2W/cm 2 . Results of our measurements have shown that thermocromic tile can be used for quality control of ultrasound transducers in the hospital environment. Experimental results show that proposed method can be used to distinguish highly non - uniform ultrasound beams with high value of BNR. Influence of exposure duration on obtained ERA and BNR values was also analysed. Our results show that values for ERA increase with insonation time, while BNR values decrease. In order to compare our results with theory we have estimated temperature rise in thermochromic material experimentally and compare it with theoretical prediction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: The goal of this work is to provide a large and consistent set of data for detector-specific output correction factors, k Q clin , Q ref f clin , f ref , for small static fields for seven solid-state detectors and to determine field output factors, Ω Q clin , Q ref f clin , f ref , using EBT3 radiochromic films and W1 plastic scintillator as reference detectors on two different linear accelerators and four megavoltage photon beams. Consistent measurement conditions and recommendations given in the International Code of Practice TRS-483 for small-field dosimetry were followed throughout the study., Methods: Ω Q clin , Q ref f clin , f ref were determined on two linacs, Elekta Versa HD and Varian TrueBeam, for 6 and 10 MV beams with and without flattening filter and for nine fields ranging from 0.5 × 0.5 cm 2 to 10 × 10 cm 2 . Signal readings obtained with EBT3 radiochromic films and W1 plastic scintillator were fitted by an analytical function. Volume averaging correction factors, determined from two-dimensional (2D) dose matrices obtained with EBT3 films and fitted to bivariate Gaussian function, were used to correct measured signals. k Q clin , Q ref f clin , f ref were determined empirically for six diodes, IBA SFD, IBA Razor, PTW 60008 P, PTW 60012 E, PTW 60018 SRS, and SN EDGE, and a PTW 60019 microDiamond detector., Results: Field output factors and detector-specific k Q clin , Q ref f clin , f ref are presented in the form of analytical functions as well as in the form of discrete values. It is found that in general, for a given linac, small-field output factors need to be determined for every combination of beam energy and filtration (WFF or FFF) and field size as the differences between them can be statistically significant (P < 0.05). For different beam energies, the present data for k Q clin , Q ref f clin , f ref are found to differ significantly (P < 0.05) from the corresponding data published in TRS-483 mostly for the smallest fields (<1.5 cm). For the PTW microDiamond detector, statistically significant differences (P < 0.05) between k Q clin , Q ref f clin , f ref values were found for all investigated beams on an Elekta Versa HD linac for field sizes 0.5 × 0.5 cm 2 and 0.8 × 0.8 cm 2 . Significant differences in k Q clin , Q ref f clin , f ref between beams of a given energy but with and without flattening filters are found for measurements made in small fields (<1.5 cm) at a given linac. Differences in k Q clin , Q ref f clin , f ref are also found when measurements are made at different linacs using the same beam energy filtration combination; for the PTW microDiamond detector, these differences were found to be around 6% and were considered as significant., Conclusions: Selection of two reference detectors, EBT3 films and W1 plastic scintillator, and use of an analytical function, is a novel approach for the determination of Ω Q clin , Q ref f clin , f ref for small static fields in megavoltage photon beams. Large set of k Q clin , Q ref f clin , f ref data for seven solid-state detectors and four beam energies determined on two linacs by a single group of researchers can be considered a valuable supplement to the literature and the TRS-483 dataset., (© 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Human monocytes and dendritic cells express transient receptor potential vanilloid 1 (TRPV1) which may play a role in mediating the inflammatory, immune and cancer surveillance responses of these cells. The aim of the present study was to investigate TRPV1 expression and function in THP-1 monocytic cells. RT-PCR and Western blot were used to detect TRPV1. The metabolic activity and viability of THP-1 cells following exposure to vanilloids was assessed using resorufin production from rezazurin. Cytokine release was measured using ELISA. TRPV1 was expressed in cultured THP-1 monocytic cells and naïve monocytes. Lower concentrations (<250 μM) of capsaicin, but not other putative TRPV1 agonists, were shown to stimulate cell metabolic activity, whereas at concentrations >250 μM, all agonists decreased metabolic activity. Capsaicin-stimulated THP-1 metabolic activity was blocked by the TRPV1 antagonist, 5-iodo-resiniferatoxin (5'-IRTX), whereas the decline in resorufin production by THP-1 cells at higher capsaicin concentrations (due to cell death), was not affected by 5'-IRTX. Finally, capsaicin (≤125 μM) significantly increased lipopolysaccharide-stimulated IL-6 and TNF-α release from THP-1 cells, whereas phytohaemagglutinin-stimulated IL-1β, TNF-α, MCP-1 and IL-6 release were concentration-dependently inhibited by capsaicin. Modulation of IL-1β release was not TRPV1 mediated. Overall, these results show that functional TRPV1 channels are present in naïve monocytes and THP-1 cells, and when activated, increase cell metabolic activity. In addition, capsaicin modifies cytokine release from THP-1 cells and induces cell death, most likely by a mechanism that is independent of TRPV1 activation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The development of a vaccine against human cytomegalovirus (CMV) has been a subject of long-term medical interest. The research during recent years identified CMV as an attractive vaccine vector against infectious diseases and tumors. The immune response to CMV persists over a lifetime and its unique feature is the inflationary T cell response to certain viral epitopes. CMV encodes numerous genes involved in immunoevasion, which are non-essential for virus growth in vitro . The deletion of those genes results in virus attenuation in vivo , which enables us to dramatically manipulate its virulence and the immune response. We have previously shown that the murine CMV (MCMV) expressing RAE-1γ, one of the cellular ligands for the NKG2D receptor, is highly attenuated in vivo but retains the ability to induce a strong CD8 + T cell response. Here, we demonstrate that recombinant MCMV expressing high affinity NKG2D ligand murine UL16 binding protein-like transcript (MULT-1) (MULT-1MCMV) inserted in the place of its viral inhibitor is dramatically attenuated in vivo in a NK cell-dependent manner, both in immunocompetent adult mice and in immunologically immature newborns. MULT-1MCMV was more attenuated than the recombinant virus expressing RAE-1γ. Despite the drastic sensitivity to innate immune control, MULT-1MCMV induced an efficient CD8 + T cell response to viral and vectored antigens. By using in vitro assay, we showed that similar to RAE-1γMCMV, MULT-1 expressing virus provided strong priming of CD8 + T cells. Moreover, MULT-1MCMV was able to induce anti-viral antibodies, which after passing the transplacental barrier protect offspring of immunized mothers from challenge infection. Altogether, this study further supports the concept that CMV expressing NKG2D ligand possesses excellent characteristics to serve as a vaccine or vaccine vector.

Advanced dose calculation algorithms for radiation therapy treatment planning can report external beam photon dose 2-sided, in terms of dose-to-medium (D m ) and dose-to-water (D w ). The purpose of our study was to determinate the effect of D w and D m reporting modes built in Elekta Monaco treatment planning system on intensity-modulated radiotherapy dose distributions for patients with nasopharyngeal cancer. For 13 patients involved in this retrospective study, 2 plans were created: 1 using D w and another according to D m reporting mode. Treatment plans were normalized such that 100% planning target volume should be covered by 95% of prescribed dose. Dose-volume constraints were assigned according to international standards. The comparison between dose distributions was performed evaluating quantities important for respective volumes of interest. For target volumes, heterogeneity index and conformity index methodology were used along with the maximum dose concept. Also, for the comparisons over particular organ at risk, maximum dose or mean dose as well as dose-volume concepts were used. For all target volumes and majority of organs at risk, the differences between 2 reporting modes are statistically insignificant, but this is not the case for bony structured organs at risks: mandible and cochlea. It was observed that D w is higher than D m with mean difference of 9.91% (p = 0.000009) of the mandible volume covered with 70 Gy. The same trend was observed for left and right cochlea with difference in mean dose of 8.74% (p = 0.037) and 6.87% (p = 0.029), respectively. The comparative analysis of dosimetric parameters in this study shows that the selection of reporting modes in Monaco treatment planning system can produce dose differences up to 15% in high-density volumes such as mandible and cochlea, which might have clinical consequences., (Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Natural killer group 2 member D (NKG2D) is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ, and CD8 + T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8 + T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here, we studied the impact of NKG2D on effector CD8 + T-cell formation. NKG2D deficiency that is restricted to murine CD8 + T cells did not impair antigen-specific T-cell expansion following mouse CMV and lymphocytic choriomeningitis virus infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8 + T cells via the Dap10 signaling pathway. T-cell development, homing, and proliferation were not affected by NKG2D deficiency and cytotoxicity was only impaired when strong T-cell receptor (TCR) stimuli were used. Transfer of antigen-specific CD8 + T cells demonstrated that NKG2D deficiency attenuated their capacity to reduce viral loads. The inability of NKG2D-deficient cells to produce cytokines could be overcome with injection of IL-15 superagonist during priming. In summary, our data show that NKG2D has a nonredundant role in priming of CD8 + T cells to produce antiviral cytokines., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: This study presents national surveys of patient exposure from nuclear medicine (NM) diagnostic procedures in 2010 and 2015 in the Republic of Croatia., Methods: The survey was performed according to the European Commission Dose DataMed (DDM) project methodology. 28 most frequent NM diagnostic procedures were identified. Data about frequencies of procedures and average administered activities of radioisotopes used in those procedures were collected. Average administered activities were converted to effective doses according to the dose conversion coefficients. Then the collective effective dose to the population and an effective dose per capita were calculated based on the number of the most frequent NM diagnostic procedures and the average effective dose per procedure., Results: In 2010, 41200 NM diagnostic procedures led to 146.7 manSv collective effective dose to the population and in 2015, 42000 NM diagnostic procedures led to 146.8 manSv collective effective dose to the population. The frequencies of NM diagnostic procedures were 9.7 and 9.8 annually per 1000 population with 34.1 μSv and 34.2 μSv effective dose per capita for 2010 and 2015, respectively. The main contributors to the annual collective dose from NM in Croatia are examinations of the bone, heart, thyroid and PET/CT tumour diagnostic. Average administered activities have not changed considerably from 2010 to 2015. Nevertheless, within the frequency of some of the procedures, significant changes were found in five-year period., Conclusions: Frequencies, average administered activities and collective effective dose to the population from NM diagnostic procedures in Croatia are comparable to the values reported by other European surveys. Changes were found between 2010 and 2015 and we intend to perform this study periodically to identify possible trends, but also to raise awareness about the potential dose optimization.

NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers. As a result, NKG2D-deficient mice produce significantly less Ag-specific IgM Abs upon immunization with T cell-independent Ags, and they are more susceptible to Gram-negative sepsis. Klrk1 -/- B1a cells are also functionally impaired and they fail to provide protection against Francisella novicida upon adoptive transfer. Using mixed bone marrow chimeric mice, we show that the impact of NKG2D deficiency on B1a cell development is cell intrinsic. No changes in homeostatic turnover and homing of B cells were detectable, limiting the effects of NKG2D to modulation of the hematopoietic development of B1a cells. Using conditional ablation, we demonstrate that the effect of NKG2D on B1a cell development occurs at a developmental stage that precedes the common lymphoid progenitor. Our findings reveal an unexpected new role for NKG2D in the regulation of B1a cell development. The protective effects of this activating receptor therefore reach beyond that of cytotoxic cells, stimulating the immune system to fight bacterial infections by promoting development of innate-like B cells., (Copyright © 2017 by The American Association of Immunologists, Inc.)

In addition to their role as effector cells in virus control, natural killer (NK) cells have an immunoregulatory function in shaping the antiviral T-cell response. This function is further pronounced in perforin-deficient mice that show the enhanced NK-cell proliferation and cytokine secretion upon mouse cytomegalovirus (MCMV) infection. Here, we confirmed that stronger activation and maturation of NK cells in perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of perforin, we compared the response of NK cells that express or do not express perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that perforin plays an intrinsic role as a feedback mechanism in the regulation of NK-cell proliferation during viral infections.

The implementation of the non-standardized method developed at the National Physical Laboratory (UK) supporting the quality assurance of therapeutic ultrasonic beam parameters within a clinical environment is presented. The method consists of exposing an acoustic absorber tile, part of which contains a thermochromic pigment, to the ultrasonic beam, thereby forming an image of the two-dimensional intensity profile of the transducer. Nine different physiotherapy ultrasound treatment heads currently used clinically were tested using this method. Thermochromic images were postprocessed in order to estimate the Effective Radiating Area (ERA) for treatment heads operating within the frequency range from 1 MHz to 3.2 MHz, and nominal applied intensities in the range of 1-3 W/cm(2). Experimental results and comparisons with manufacturer specified values of ERA are presented. Differences in the experimentally derived results and the manufacturer values are typically well within 25%. The root-mean squared difference calculated over the nine treatment heads is 15.1%, with the thermochromic material tended to underestimate the ERA., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Implementation of advanced techniques in clinical practice can greatly improve the outcome of radiation therapy, but it also makes the process much more complex with a lot of room for errors. An important part of the quality assurance program is verification of treatment planning system (TPS). Dosimetric verifications in anthropomorphic phantom were performed in 4 centers where new systems were installed. A total of 14 tests for 2 photon energies and multigrid superposition algorithms were conducted using the CMS XiO TPS. Evaluation criteria as specified in the International Atomic Energy Agency Technical Reports Series (IAEA TRS) 430 were employed. Results of measurements are grouped according to the placement of the measuring point and the beam energy. The majority of differences between calculated and measured doses in the water-equivalent part of the phantom were in tolerance. Significantly more out-of-tolerance values were observed in "nonwater-equivalent" parts of the phantom, especially for higher-energy photon beams. This survey was done as a part of continuous effort to build up awareness of quality assurance/quality control (QA/QC) importance in the Croatian radiotherapy community. Understanding the limitations of different parts of the various systems used in radiation therapy can systematically improve quality as well., (Copyright © 2013 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Implementation of advanced radiation therapy techniques in clinical practice can greatly improve tumour control and normal tissue sparing. An important part of this implementation is quality control (QC) of every part of the radiotherapy process, as it helps to detect errors and provides instant remedy. This increases the probability of successful radiation treatment and ensures patient radiation safety. Every radiotherapy quality assurance (QA) programme is based on quality control of radiotherapy equipment. The aim of our survey was to review QC practices in a number of radiotherapy centres in Croatia. As a first step, we defined a set of tests to check different parameters of linear accelerators and simulators in these centres. The tests were defined and performed according to protocols developed at two university hospitals. Test results varied largely between the centres. This calls for harmonisation of QC protocols.

An external beam radiotherapy (EBRT) using megavoltage beam of linear accelerator is usually the treatment of choice in cancer patients. The goal of EBRT is to deliver the prescribed dose to the target volume, with as low as possible dose to the surrounding healthy tissue. A large number of procedures and different professions involved in radiotherapy, uncertainty of equipment and daily patient set-up errors can cause a difference between the planned and delivered dose.We investigated a part of this difference caused by measuring daily patient set-up errors for 35 patients. These set-up errors were simulated on five patients, using 3D treatment planning software XiO. The simulation investigated differences in dose distributions between the planned and shifted geometry. Additionally, we investigated the influence of the error on treatment plan selection by analysing changes in dose volume histograms, planning target volume conformity index (CIPTV), and homogeneity index (HI).Simulations showed that patient daily set-up errors can cause significant differences between the planned and actual dose distributions. Moreover, for some patients, those errors could affect the choice of treatment plan since CIPTV fell under 97%. Surprisingly, HI was not as sensitive to set-up errors as CIPTV. Our results have confirmed the need to minimise daily set-up errors through quality assurance programmes.

Ethnopharmacological Relevance: Carpobrotus rossii (CR) has a history of use as a food and therapeutic agent by Australian indigenous peoples and early European settlers and is believed to contain a number of pharmacologically active polyphenolic compounds., Aims of the Study: Oxidation of low density lipoprotein (LDL), platelet aggregation, and inflammation contribute to the development and progression of atherosclerosis. The aim of the present study was to investigate the antioxidant, antiplatelet and anti-inflammatory activity of CR extract using human blood components., Materials and Methods: An assay employing in vitro copper-induced oxidation of serum lipids was used to assess antioxidant activity of CR extract (and tannin, flavonoid and pre- and post-flavonoid fractions). The effects of CR extract on ADP- and collagen-induced platelet aggregation, and on basal (unstimulated) and lipopolysaccharide (LPS)- and phytohaemagglutinin A (PHA)-stimulated cytokine release from peripheral blood mononuclear cells (PBMC) were also investigated., Results: CR extract increased the lag time of serum oxidation (maximum of ∼4-fold at 20μg/ml) in a concentration-dependent manner. The antioxidant activity resided only in the tannin and post-flavonoid fractions. CR had no effect on ADP-induced platelet aggregation, but significantly decreased collagen-induced platelet aggregation. LPS, but not PHA, significantly increased the release of IL-1β and TNF-α from PBMC. CR extract alone inhibited monocyte chemoattractant protein (MCP)-1 release and in the presence of LPS, inhibited IL-10, TNF-α and MCP-1 release compared to LPS alone., Conclusion: CR has significant in vitro antioxidant, antiplatelet and, potentially, anti-inflammatory activity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)