A novel method to determine linac mechanical isocenter position and size and examples of specific QA applications.

The most important geometric characteristic of stereotactic treatment is the accuracy of positioning the target at the treatment isocenter and the accuracy of directing the radiation beam at the treatment isocenter. Commonly, the radiation isocenter is used as the reference for the treatment isocenter, but its method of localization is not strictly defined, and it depends on the linac-specific beam steering parameters. A novel method is presented for determining the linac mechanical isocenter position and size based on the localization of the collimator axis of rotation at arbitrary gantry angle. The collimator axis of rotation position is determined from the radiation beam center position corrected for the focal spot offset. The focal spot offset is determined using the image center shift method with a custom-design rigid phantom with two sets of ball-bearings. Three specific quality assurance (QA) applications and assessment methods are also presented to demonstrate the functionality of linac mechanical isocenter position and size determination in clinical practice. The first is a mechanical and radiation isocenters coincidence test suitable for quick congruence assessment of these two isocenters for a selected energy, usually required after a nonroutine linac repair and/or energy adjustment. The second is a stereotactic beam isocentricity assessment suitable for pretreatment stereotactic QA. The third is a comprehensive linac geometrical performance test suitable for routine linac QA. The uncertainties of the method for determining mechanical isocenter position and size were measured to be 0.05 mm and 0.04 mm, respectively, using four available photon energies, and were significantly smaller than those of determining the radiation isocenter position and size, which were 0.36 mm and 0.12 mm respectively. It is therefore recommended that the mechanical isocenter position and size be used as the reference linac treatment isocenter and a linac mechanical characteristic parameter respectively.

Towards zero radiation isocentre size: minimising radiation beam isocentricity on Elekta linear accelerators by means of optimising look-up tables.

The most important geometric characteristics of SRS/SBRT treatments are precise target localisation and precise aiming of the radiation beam at the target. The AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS/SBRT recommends that the radiation isocentricity (i.e. beam deviation from the isocentre) should not exceed 1 mm for SRS and 1.5 mm for SBRT. Minimising the beam deviations from the treatment target, largely due to the gantry sag, can improve the accuracy of radiosurgery and stereotactic treatments and commonly beam steering parameters are optimised to achieve this objective. This study aims to investigate, as a proof of concept, if it is possible to eliminate the beam deviations on Elekta linear accelerators altogether by optimising gantry angle dependent beam steering parameters, as stored in look-up tables. The investigation used the EPID-based Winston-Lutz test at 13 gantry angles separated every 30° (from - 180° to + 180°). Elekta linacs have two look-up tables that can be customised explicitly for radial beam angle and transverse beam position. Modifications of the radial look-up table were limited by the radial beam asymmetry inhibit of more than 5%, as measured by the linac in-built ionisation chamber. Therefore, only small radial beam deviation reductions of 0.1 mm were achieved (on average from 0.37 to 0.26 mm) while radial beam symmetry changed significantly by up to ± 7%, depending on the gantry angle as measured by the IC Profiler™. The optimised transverse look-up table resulted in reduction of transverse beam deviations to almost zero (on average from 0.20 to 0.03 mm), however, that changed the transverse beam symmetry by almost a constant value of 1%, as measured by the IC Profiler™. Ideally, two additional look-up tables are needed for effective beam steering, one for radial beam position and one for transverse beam angle. Four look-up tables in total would enable customising beam centre position and beam symmetry at any gantry angle that would minimize radiation isocentre size without compromising beam symmetry.

Practical beam steering of X-ray beams on Elekta accelerators: The effect of focal spot alignment on beam (symmetry and position) and radiation isocentre (size and position).

Acceptance and commissioning of a linear accelerator is the process of preparing it for clinical use. One of the initial important dosimetric tasks for X-ray beam set-up and use is to optimise the trajectory of the electron beam before it hits the target (focal spot). The main purpose of this study is to characterise the effect of the focal spot position (offset) on the photon beam symmetry and centre position, as well as on linac radiation isocentre size and position for an Elekta Synergy® linac. For this machine, the initial electron beam steering control items 2T and Bending F were altered to steer the beam in both transverse and radial directions respectively. The IC Profiler™ was utilised to measure the photon beam symmetry and centre position; the electronic portal imaging device (EPID) and the authors' published ready-to-go procedure were used to measure the focal spot offset; and the radiation isocentre size and position were measured using the EPID, the Elekta ball-bearing phantom and in-house software. It was observed that for the 6MV beam investigated, beam symmetry shows a high dependency on the focal spot position, with correlation coefficients of 8.6%/mm and 5.6%/mm in transverse and radial directions respectively. The radiation isocentre size shows dependency of 1.7 mm/mm on focal spot position in the transverse direction only. The radiation isocentre longitudinal position shows dependency of - 1.8 mm/mm on the focal spot position in the radial direction only. The beam centre position is directly correlated with the focal spot position in both directions, but the correlation coefficient depends on the collimation used in a given direction i.e. MLC (- 1.5 mm/mm) or diaphragms (- 0.8 mm/mm). Based on the results, a fast beam steering method was proposed and used successfully on an Elekta Versa HD™ linac, utilizing the IC Profiler™ and its associated Gantry Mounting Fixture™ (GMF) to efficiently and effectively optimise beam steering parameters for clinical use. Independent validation of the method showed that focal spot offsets and beam symmetries in terms of absolute deviations were on average 0.08 ± 0.05 mm (1SD) and 0.70 ± 0.27% (1SD) respectively.

Assessment of error in the MV radiation isocenter position calculated with the Elekta XVI software.

The assessment of the coincidence of imaging and radiation isocenters is an important task of regular quality assurance of medical linear accelerators (linacs) as recommended in national and international quality assurance guidelines. A previously reported investigation of the accuracy of the Elekta XVI software to localize the linac radiation isocenter, by comparing statistically with other independent software, has shown some discrepancies at the sub-mm level. A further investigation is carried out here using a set of reference images and mathematical operations to observe how the Elekta XVI software analyses them. Symmetric mathematical operations on reference images should result in symmetrical outcomes. Three different rotation functions are used in increasing degree of complexity to characterize the Elekta XVI software error in the linac radiation isocenter position. No independent algorithms or phantoms are used in this methodology. The magnitude and direction of the radiation isocenter localization error has been determined to be consistently 0.13 mm or 0.14 mm in the longitudinal direction towards the target depending on the case. The radiation isocenter localization error comprises two separated errors of the Ball Bearing Center by 0.13 mm and MV Field Center by either 0.00 mm or -0.01 mm in the longitudinal direction towards the target. The calculation of the MV Field Center is influenced by the polymethyl methacrylate rod supporting the ball-bearing. The precise value and the root cause of the error cannot be assessed due to the rounding effect of the results reported by the Elekta XVI software and lack of access to the source code.

Assessing the dependency of the uncertainties in the Elekta Agility MLC calibration procedure on the focal spot position.

The effectiveness of radiotherapy treatments depends on the accuracy of the dose delivery process. The majority of radiotherapy courses are delivered on linear accelerators with a Multi Leaf Collimator (MLC) in 3D conformal Radiation Therapy, Intensity Modulated Radiation Therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT) modes that require accurate MLC positioning. This study investigates the MLC calibration accuracy, following manufacturer procedures for an Elekta Synergy linac with the Agility head, against the radiation focal spot offset (alignment with the collimator axis of rotation). If the radiation focal spot is not aligned ideally with the collimator axis of rotation then a systematic error can be introduced into the calibration procedure affecting absolute MLC leaf positions. Calibration of diaphrams is equally affected; however they are not investigated here. The results indicate that an estimated 0.15 mm MLC uncertainty in all MLC leaves positions can be introduced due to uncertainty of the radiation focal spot position of 0.21 mm.

The effects of humic water on endothelial cells under hyperglycemic conditions: inflammation-associated parameters.

Humic waters (HW) are globally unique, deep underground, dark-brown waters containing humic acids, and they present numerous therapeutic activities including anti-inflammatory. In the present study, we use HW from source in Poland. Diabetes has become an epidemic and is a risk factor of cardiovascular diseases. Hyperglycemia in diabetes is responsible for damaging of the endothelium and increases inflammation on the surface of the vascular lining. The inflammatory process in diabetes is associated with the secretion of inflammatory cytokines by endothelial cells, e.g., tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), and with the reduction of cell proliferation. In the study, we used cultures of endothelial cells (HUVEC line-human umbilical vein endothelial cells) with the addition 30 mM/L of glucose in the culture medium which imitated the conditions of uncontrolled diabetes. The addition of HW in the proper volume to the culture medium causes reduction of inflammation by significant decrease in inflammatory cytokines such as TNFα and IL-6 and also leads to enhancement of the cell proliferation. It appears that the adverse effects of hyperglycemia on vascular endothelial cells may be corrected by addition of humic water. The above promising results of in vitro tests provide an opportunity to the possible use of humic water in the supportive treatment of endothelial dysfunction disorders in diabetes. However, this issue requires further clinical research.

Beam focal spot position determination for an Elekta linac with the Agility® head; practical guide with a ready-to-go procedure.

A novel phantomless, EPID-based method of measuring the beam focal spot offset of a linear accelerator was proposed and validated for Varian machines. In this method, one set of jaws and the MLC were utilized to form a symmetric field and then a 180o collimator rotation was utilized to determine the radiation isocenter defined by the jaws and the MLC, respectively. The difference between these two isocentres is directly correlated with the beam focal spot offset of the linear accelerator. In the current work, the method has been considered for Elekta linacs. An Elekta linac with the Agility® head does not have two set of jaws, therefore, a modified method is presented making use of one set of diaphragms, the MLC and a full 360o collimator rotation. The modified method has been tested on two Elekta Synergy® linacs with Agility® heads and independently validated. A practical guide with instructions and a MATLAB® code is attached for easy implementation.

Beam focal spot position: The forgotten linac QA parameter. An EPID-based phantomless method for routine Stereotactic linac QA.

Modern day Stereotactic treatments require high geometric accuracy of the delivered treatment. To achieve the required accuracy the IGRT imaging isocenter needs to closely coincide with the treatment beam isocenter. An influence on this isocenter coincidence and on the spatial positioning of the beam itself is the alignment of the treatment beam focal spot with collimator rotation axis. The positioning of the focal spot is dependent on the linac beam steering and on the stability of the monitor chamber and beam steering servo system. As such, there is the potential for focal spot misalignment and this should be checked on a regular basis. Traditional methods for measuring focal spot position are either indirect, inaccurate, or time consuming and hence impractical for routine use. In this study a novel, phantomless method has been developed using the EPID (Electronic Portal Imaging Device) that utilizes the different heights of the MLC and jaws. The method has been performed on four linear accelerators and benchmarked against an alternate ion chamber-based method. The method has been found to be reproducible to within ±0.012 mm (1 SD) and in agreement with the ion chamber-based method to within 0.001 ± 0.015 mm (1 SD). The method could easily be incorporated into a departmental routine linac QA (Quality Assurance) program.

Withdrawal from bariatric treatment - an analysis under various demographic conditions.

Poland is high on a list of countries affected by epidemics of obesity, a problem that has especially suddenly increased in the post-transformation period. MATERIALS AND METHOD: Documentation of 115 subsequent patients diagnosed with grade 3 obesity, considered eligible for surgical treatment, was analysed since 2015. A subgroup of 68 patients was selected from this group and the included patients who decided to cancel their treatment at various stages. Their history since presentation at the obesity treatment centre, BMI with its history, age, education and place of residence were analysed, followed by a telephone survey. 42 patients were finally contacted. Special attention was placed on the analysis of patients taking into account their place of residence. Patients were divided into inhabitants of rural and urban areas. RESULTS: In the study group of 68 patients, 19 (27.9%) were inhabitants of rural areas and 49 (72.1%) of urban areas. Women accounted for 67.6%, and men for 32.4%. The mean age of patients when they presented for treatment was 43 years. On average, men presented 5 years later compared to women. The mean BMI on qualification for treatment of obesity was 47.6 kg/m2. The mean BMI max - 49.6 kg/m2. There were no differences regarding education in both populations. Despite the lack of differences regarding changes in the BMI since withdrawal from treatment, as many as 63% of patients from rural areas reached the BMI max in this time. CONCLUSIONS: There were demographic differences between the degree of obesity observed among patients receiving bariatric treatment, and inhabitants of urban areas were favoured. Patients from rural areas who withdrew from bariatric treatment and were left without medical care significantly more often achieved their maximum body weight, when compared to those living in urban areas. The active participation of physicians, both specialists and general practitioners, in the life of obese patients is imperative.

Left-sided breast cancer loco-regional radiotherapy with deep inspiration breath-hold: Does volumetric-modulated arc radiotherapy reduce heart dose further compared with tangential intensity-modulated radiotherapy?

INTRODUCTION: Left-sided breast cancer radiotherapy has been associated with an increase in cardiac mortality. This study investigated the potential heart-sparing effect of volumetric-modulated arc radiotherapy (VMAT). We compared VMAT to tangential intensity-modulated radiotherapy (t-IMRT) in the loco-regional treatment of left-sided breast cancer, including internal mammary nodal irradiation, based on deep inspiration breath-hold (DIBH) and free-breathing (FB). METHODS: Radiotherapy for 15 patients was re-planned. Four plans were compared: t-IMRT-DIBH; VMAT-DIBH; t-IMRT-FB; VMAT-FB. Prescribed dose was 50 Gy in 25 fractions. T-IMRT plans were generated using tangentially orientated fields. VMAT plans were generated using two partial arcs (average arc 190°). RESULTS: Mean heart dose (MHD) was 5 ± 2.4 Gy, 5.7 ± 1.4 Gy, 9.7 ± 3.3 Gy and 8.1 ± 2.0 Gy for t-IMRT-DIBH, VMAT-DIBH, IMRT-FB and VMAT-FB respectively. The difference in MHD between IMRT-DIBH and VMAT-DIBH was not significant (P = 0.14). VMAT-DIBH significantly spared the volume of heart irradiated to doses of 20 Gy and above (p < 0.05), however, resulted in a significantly higher V5 Gy (P < 0.001), compared to t-IMRT-DIBH. VMAT-DIBH resulted in higher combined lung mean (11 ± 0.8 Gy vs. 8.8 ± 1.1 Gy, P < 0.001) and higher contralateral breast mean dose (5 ± 1 Gy vs. 1.6 ± 1.2 Gy, P < 0.001) compared with t-IMRT-DIBH. CONCLUSIONS: On average, there was no significant difference in MHD between VMAT-DIBH and t-IMRT-DIBH. However, VMAT-DIBH was found to benefit a select group of patients. For patients in whom the MHD was >6.3 Gy with t-IMRT-DIBH, the use of VMAT-DIBH resulted in a benefit in reducing the MHD.

Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals.

There is strong evidence for the presence of a functional renin-angiotensin system in human adipose tissue. The aim of our study was to investigate the association of polymorphic variants of angiotensin-converting enzyme gene (ACE I/D) and angiotensin II type I receptor gene (AGTR1 A1166C) with extreme obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to examine their combined effect on extremely obese patients. Overall, no significant associations were detected between ACE and AGTR1 gene polymorphisms and extreme obesity. However, extremely obese patients with T2DM showed an increased frequency of ACE II genotype compared with controls (p<0.05) and with non-diabetic extremely obese patients (p<0.01). The results suggest that II genotype of ACE was a significant contributor to extreme obesity in AA homozygotes of AGTR1 gene, regardless of the presence of T2DM. Moreover, the analysis of genetic polymorphisms demonstrated that ACE II and AGTR1 AC genotypes were most frequently observed in patients with extreme obesity and T2DM. On the basis of our results, we suggest that ACE II homozygosity may be a significant predictor of extreme obesity and T2DM and that the interaction between ACE and AGTR1 genes may be considered a predisposing factor for extreme obesity and extreme obesity-associated T2DM development.

Correlations between polymorphisms in genes coding elements of dopaminergic pathways and body mass index in overweight and obese women.

INTRODUCTION: Dopamine is considered to be crucial for food craving and intake, drug abuse and electrical brain stimulation. Increased levels of dopamine occur after energy intake in the dorsal striatum. In the ventral tagmental area, dopamine is responsible for motivation. There is a natural synaptic dopamine level, and as a result its activity is controlled by density of receptors, amount of released neurotransmitter, and defectiveness of re-uptake by specific transporters. In our study, we wanted to investigate if there is a correlation between mean BMI values and VNTR polymorphisms in SLC6A3 (rs28363170) and DRD4 genes. MATERIAL AND METHODS: Chosen gene fragments were amplified using polymerase chain reaction on the DNA template obtained from 506 women. The products of the reaction were electrophoresed and visualised in 3% agarose gel. The genotyping data was analysed with Kruskal-Wallis tests (p 〈 0.05). RESULTS: In the case of SLC6A3, statistically significant differences in mean BMI were found in the group of obese women (p 〈 0.05) but not for the whole population of women with normal weight or with overweight (p 〉 0.05). The mean BMI was higher for the SS genotype than for combined LL and LS genotypes. The difference in mean BMI values for variants of DRD4 was significant for the whole studied population and in the obese group (p 〉 0.05), and the higher value was correlated with the presence of a variant with seven or more repeats of 48 bp motif. CONCLUSIONS: When the two analysed polymorphisms were combined, the spread between the mean BMI values became greater than for single genes. This suggests that the effect on body mass of these two polymorphisms may combine and cause hypo-functionality of the dopaminergic reward system.

An automatic method of the isocentre position verification for micromultileaf collimator based radiosurgery system.

An efficient procedure has been developed using an electronic portal imaging device (EPID) and in-house written software for verification of a target simulator alignment with the radiation isocentre. A 5 mm tungsten ball is aligned to a linac isocentre based on a lasers intersection point. The BrainLab(®) m3™ add-on multileaf collimator (MLC) forms a rectangular open field of 1.8 × 1.8 cm(2). At five different gantry and couch positions, EPID images are acquired. A computer search algorithm determines the centres of both a radiation field and a tungsten ball for each image. Based on the geometric differences between those centres, the optimum three-dimensional shift of a tungsten ball is calculated in order to minimise the misalignment error between a target simulator and a radiation isocentre. A decision can then be made whether or not the tungsten ball and lasers intersection point should be corrected. The accuracy and precision of the procedure has been tested and found to be 0.04 and 0.24 mm respectively at 95% confidence interval. The procedure is also quicker, easier and more reliable to perform compared to the previous method based on irradiating a radiographic film.