On dosimetric characteristics of detectors for relative dosimetry in small fields: a multicenter experimental study.

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 HDTMor Varian TrueBeamTMlinear 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 coefficientr2), it was found that 100% of the data fulfill the criteriar2> 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).

Determination of volume averaging correction factors using an elliptical absorbed dose model for Gamma Knife Perfexion.

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.

Reduction of SPECT acquisition time using deep learning: A phantom study.

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.

Dosimetric accuracy of three dose calculation algorithms for radiation therapy of in situ non-small cell lung carcinoma.

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 (MCDm) and dose to water in medium (MCDw,) 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 (D2%), mean dose (Dmean) and percentage of volumes covered by prescribed dose (V70Gy). For organs at risk (OARs), Dmean and percentage of volume receiving 20 Gy and 5Gy (V20Gy, V5Gy) were analysed. Results: Statistically significant difference for GTVs was observed between MCDw and SS algorithm in mean dose only. For planning target volumes (PTVs), statistically significant differences were observed in prescribed dose coverage for CC, MCDm and MCDw. The differences in mean CI value for the CC algorithm and mean HI value for MCDm and MCDw were statistically significant. There is a statistically significant difference in the number of MUs for MCDm and MCDw 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.

National reference levels of CT procedures dedicated for treatment planning in radiation oncology.

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 (CTDIvol), 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 CTDIvol were calculated for each acquisition protocol. Third quartiles of the median CTDIvol 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 CTDIvol), RT Thorax (79.7% for DLP) and RT H&N (21.2% for scan length). RT Head had the lowest CoV for CTDIvol (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 CTDIvol16cm = 62 mGy and DLP16cm = 1738 mGy.cm; for RT H&N CTDIvol16cm = 35 mGy and DLP16cm = 1444 mGy.cm; for RT Breast CTDIvol32cm = 16 mGy and DLP32cm = 731 mGy.cm; for RT Thorax CTDIvol32cm = 17 mGy and DLP32cm = 865 mGy.cm; for RT Pelvis CTDIvol32cm = 20 mGy and DLP32cm = 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.

Virtual monoenergetic dual-energy CT reconstructions at 80 keV are optimal non-contrast CT technique for early stroke detection.

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.

Use of Multiphase CT Protocols in 18 Countries: Appropriateness and Radiation Doses.

PURPOSE: To assess the frequency, appropriateness, and radiation doses associated with multiphase computed tomography (CT) protocols for routine chest and abdomen-pelvis examinations in 18 countries. MATERIALS AND METHODS: In collaboration with the International Atomic Energy Agency, multi-institutional data on clinical indications, number of scan phases, scan parameters, and radiation dose descriptors (CT dose-index volume; dose-length product [DLP]) were collected for routine chest (n = 1706 patients) and abdomen-pelvis (n = 426 patients) CT from 18 institutions in Asia, Africa, and Europe. Two radiologists scored the need for each phase based on clinical indications (1 = not indicated, 2 = probably indicated, 3 = indicated). We surveyed 11 institutions for their practice regarding single-phase and multiphase CT examinations. Data were analyzed with the Student t test. RESULTS: Most institutions use multiphase protocols for routine chest (10/18 institutions) and routine abdomen-pelvis (10/11 institutions that supplied data for abdomen-pelvis) CT examinations. Most institutions (10/11) do not modify scan parameters between different scan phases. Respective total DLP for 1-, 2-, and 3-phase routine chest CT was 272, 518, and 820 mGy·cm, respectively. Corresponding values for 1- to 5-phase routine abdomen-pelvis CT were 400, 726, 1218, 1214, and 1458 mGy cm, respectively. For multiphase CT protocols, there were no differences in scan parameters and radiation doses between different phases for either chest or abdomen-pelvis CT (P = 0.40-0.99). Multiphase CT examinations were unnecessary in 100% of routine chest CT and in 63% of routine abdomen-pelvis CT examinations. CONCLUSIONS: Multiphase scan protocols for the routine chest and abdomen-pelvis CT examinations are unnecessary, and their use increases radiation dose.

Optimization of paranasal sinus CT procedure: Ultra-low dose CT as a roadmap for pre-functional endoscopic sinus surgery.

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 (CTDIvol 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 (CTDIvol 2.2 mGy; DLP 22.9 mGy.cm) with up to 60% lower dose compared to prior standard-dose CT (CTDIvol 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.

Experimental validation of Monte Carlo based treatment planning system in bone density equivalent media.

Introduction 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. Materials and methods In our study, we used a 6 MV photon beam from a linear accelerator. To evaluate the accuracy of the TPS calculation approaches, measurements with a Farmer type chamber in a semi-anthropomorphic phantom were compared to those obtained by two calculation options. The comparison was made for three parts of the phantom having different densities, with a focus on the BDE part. Results Measured and calculated doses were in agreement for water and lung equivalent density materials, regardless of the calculation mode. However, in the BDE part of the phantom, mean dose differences between the calculation options ranged from 5.7 to 8.3%, depending on the method used. In the BDE part of the phantom, neither of the two calculation options were consistent with experimentally determined absorbed doses. Conclusions Based on our findings, we proposed a supplement to the current methodology for the verification of commercial MC based TPS by performing additional measurements in BDE material.

National survey to set diagnostic reference levels in nuclear medicine single photon emission imaging in Croatia.

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.

Output correction factors for small static fields in megavoltage photon beams for seven ionization chambers in two orientations - perpendicular and parallel.

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 cm2  × 0.5 cm2 to 10 cm2  × 10 cm2 . 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 cm2  × 0.5 cm2 to 10 cm2  × 10 cm2 , 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 cm2  × 0.8 cm2 , 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 cm2  × 0.5 cm2 . 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 cm2  × 0.5 cm2 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 cm2  × 1.0 cm2 , 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.

Determination of physiotherapy ultrasound beam quality parameters from images derived using thermochromic material.

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/cm2. 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.

A novel method for the determination of field output factors and output correction factors for small static fields for six diodes and a microdiamond detector in megavoltage photon beams.

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 cm2 to 10 × 10 cm2 . 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 cm2 and 0.8 × 0.8 cm2 . 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.

IMPLEMENTATION OF QUALITY ASSURANCE PROGRAM IN RADIOGRAPHY-2-YEAR EXPERIENCE OF COLLABORATION WITH PUBLIC HEALTH INSTITUTIONS IN WEST REGION OF CROATIA.

Quality Assurance program on using ionizing radiation is mandatory in all EU member states but this is still not implemented in most facilities in Croatia mostly because of a lack of medical physicists in diagnostic radiology. Since public health institutions in Croatia do not employ medical physicists in diagnostic radiology, collaboration between these institutions in west region of Croatia with Clinical Hospital Center Rijeka (CHC) was initiated during the year 2015. Physicists from CHC Rijeka performed periodical Quality Control (QC) tests and were included in optimization process. Results of QC tests during the period of 2 years showed a lot of improvements-equipment is maintained more frequently, some old units were replaced with new ones and all institutions acquired QC equipment so radiographers could perform daily and monthly QC tests. All these activities showed that medical physics support in radiology departments is necessary and can improve clinical practice.

Evaluation of two-dimensional dose distributions for pre-treatment patient-specific IMRT dosimetry.

Background 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. Materials and methods The research was performed using Siemens Oncor Expression linear accelerator, Siemens Somatom Open CT simulator and Elekta Monaco TPS. A 2D detector array was used to evaluate dose distribution accuracy in homogeneous, semi-anthropomorphic and anthropomorphic phantoms. Validation was based on gamma analysis with 3%/3mm and 2%/2mm criteria, respectively. Results Passing rates of the complex dose distributions degrade depending on the thickness of non-water equivalent material. They also depend on dose reporting mode used. It is observed that the passing rate decreases with plan complexity. Comparison of the data for all set-ups of semi-anthropomorphic and anthropomorphic phantoms shows that passing rates are higher in the anthropomorphic phantom. Conclusions Presented results raise a question of possible limits of dose distribution verification in assessment of plan delivery quality. Consequently, good results obtained using standard patient specific dosimetry methodology do not guarantee the accuracy of delivered dose distribution in real clinical cases.

Murine CMV Expressing the High Affinity NKG2D Ligand MULT-1: A Model for the Development of Cytomegalovirus-Based Vaccines.

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.

Comparison of calculated dose distributions reported as dose-to-water and dose-to-medium for intensity-modulated radiotherapy of nasopharyngeal cancer patients.

Advanced dose calculation algorithms for radiation therapy treatment planning can report external beam photon dose 2-sided, in terms of dose-to-medium (Dm) and dose-to-water (Dw). The purpose of our study was to determinate the effect of Dw and Dm 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 Dw and another according to Dm 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 Dw is higher than Dm 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.

Estimated collective effective dose to the population from nuclear medicine diagnostic procedures in Croatia: A comparison of 2010 and 2015.

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 stimulation of CD8+ T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice.

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.

NKG2D Promotes B1a Cell Development and Protection against Bacterial Infection.

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.