Chondrichthyan research in South America: Endocrinology overview and research trends over 50 years (1967-2016) compared to the rest of the world.

The endocrine system plays a crucial role in regulating the activity of cells and organs among vertebrates, including the class Chondrichthyes. Accordingly, Chondrichthyan endocrinology publications have been steadily increasing in the global literature. However, while interest in South American Chondrichthyan research has been growing over the last 50 years, the field of endocrinology related to Chondrichthyans has been limited. Understanding the trajectory of a scientific discipline assists researchers and stakeholders in making decisions regarding which research areas require further attention. Further, visualisation techniques based on bibliometric analysis of scientific publications assist in understanding fluctuations in the trends of specific research fields over time. In this study, Chondrichthyan research publications over time were analysed by creating visualisation maps using VOSviewer bibliometric software. Trends in South America Chondrichthyan research with an emphasis on endocrinology were explored over a 50-year period (1967-2016). These trends were compared with Chondrichthyans research worldwide for the more recent 15-year period (2002-2016). The number of South America Chondrichthyan scientific publications increased from six during the 1967-1981 period to 112 in 2016. However, only eight papers were found published in the area of Chondrichthyan endocrinology research. Fisheries, reproduction and taxonomy were the dominate research areas in South America over the 50 years. For the more recent 15 years, South American publications comprised 11% of the total literature published globally. While South America research outputs fluctuated closely with global research trends, differences appeared when comparing areas of growth. This study describes the trends in Chondrichthyan research literature globally and more specifically in South America. Although South American countries may never contribute to the same scale as the wider international scientific community, the future of Chondrichthyans would strongly benefit from the contributions of the many diverse research groups around the world.

Water and tissue equivalence of a new PRESAGE(®) formulation for 3D proton beam dosimetry: a Monte Carlo study.

PURPOSE: To evaluate the water and tissue equivalence of a new PRESAGE(®) 3D dosimeter for proton therapy. METHODS: The GEANT4 software toolkit was used to calculate and compare total dose delivered by a proton beam with mean energy 62 MeV in a PRESAGE(®) dosimeter, water, and soft tissue. The dose delivered by primary protons and secondary particles was calculated. Depth-dose profiles and isodose contours of deposited energy were compared for the materials of interest. RESULTS: The proton beam range was found to be ≈27 mm for PRESAGE(®), 29.9 mm for soft tissue, and 30.5 mm for water. This can be attributed to the lower collisional stopping power of water compared to soft tissue and PRESAGE(®). The difference between total dose delivered in PRESAGE(®) and total dose delivered in water or tissue is less than 2% across the entire water∕tissue equivalent range of the proton beam. The largest difference between total dose in PRESAGE(®) and total dose in water is 1.4%, while for soft tissue it is 1.8%. In both cases, this occurs at the distal end of the beam. Nevertheless, the authors find that PRESAGE(®) dosimeter is overall more tissue-equivalent than water-equivalent before the Bragg peak. After the Bragg peak, the differences in the depth doses are found to be due to differences in primary proton energy deposition; PRESAGE(®) and soft tissue stop protons more rapidly than water. The dose delivered by secondary electrons in the PRESAGE(®) differs by less than 1% from that in soft tissue and water. The contribution of secondary particles to the total dose is less than 4% for electrons and ≈1% for protons in all the materials of interest. CONCLUSIONS: These results demonstrate that the new PRESAGE(®) formula may be considered both a tissue- and water-equivalent 3D dosimeter for a 62 MeV proton beam. The results further suggest that tissue-equivalent thickness may provide better dosimetric and geometric accuracy than water-equivalent thickness for 3D dosimetry of this proton beam.

Water equivalence evaluation of PRESAGE(®) formulations for megavoltage electron beams: a Monte Carlo study.

To investigate the radiological water equivalency of three different formulations of the radiochromic, polyurethane based dosimeter PRESAGE(®) for three dimensional (3D) dosimetry of electron beams. The EGSnrc/BEAMnrc Monte Carlo package was used to model 6-20 MeV electron beams and calculate the corresponding doses delivered in the three different PRESAGE(®) formulations and water. The depth of 50 % dose and practical range of electron beams were determined from the depth dose calculations and scaling factors were calculated for these electron beams. In the buildup region, a 1.0 % difference in dose was found for all PRESAGE(®) formulations relative to water for 6 and 9 MeV electron beams while the difference was negligible for the higher energy electron beams. Beyond the buildup region (at a depth range of 22-26 mm for the 6 MeV beam and 38 mm for the 9 MeV beam), the discrepancy from water was found to be 5.0 % for the PRESAGE(®) formulations with lower halogen content than the original formulation, which was found to have a discrepancy of up to 14 % relative to water. For a 16 MeV electron beam, the dose discrepancy from water increases and reaches about 7.0 % at 70 mm depth for the lower halogen content PRESAGE(®) formulations and 20 % at 66 mm depth for the original formulation. For the 20 MeV electron beam, the discrepancy drops to 6.0 % at 90 mm depth for the lower halogen content formulations and 18 % at 85 mm depth for the original formulation. For the lower halogen content PRESAGE(®), the depth of 50 % dose and practical range of electrons differ from water by up to 3.0 %, while the range of differences from water is between 6.5 and 8.0 % for the original PRESAGE(®) formulation. The water equivalent depth scaling factor required for the original formulation of PRESAGE(®) was determined to be 1.07-1.08, which is larger than that determined for the lower halogen content formulations (1.03) over the entire beam energy range of electrons. All three of the PRESAGE(®) formulations studied require a depth scaling factor to convert depth in PRESAGE(®) to water equivalent depth for megavoltage electron beam dosimetry. Compared to the original PRESAGE(®) formulation, the lower halogen content formulations require a significantly smaller scaling factor and are thus recommended over the original PRESAGE(®) formulation for electron beam dosimetry.

Investigation of radiological properties and water equivalency of PRESAGE dosimeters.

PURPOSE: PRESAGE is a dosimeter made of polyurethane, which is suitable for 3D dosimetry in modern radiation treatment techniques. Since an ideal dosimeter is radiologically water equivalent, the authors investigated water equivalency and the radiological properties of three different PRESAGE formulations that differ primarily in their elemental compositions. Two of the formulations are new and have lower halogen content than the original formulation. METHODS: The radiological water equivalence was assessed by comparing the densities, interaction probabilities, and radiation dosimetry properties of the three different PRESAGE formulations to the corresponding values for water. The relative depth doses were calculated using Monte Carlo methods for 50, 100, 200, and 350 kVp and 6 MV x-ray beams. RESULTS: The mass densities of the three PRESAGE formulations varied from 5.3% higher than that of water to as much as 10% higher than that of water for the original formulation. The probability of photoelectric absorption in the three different PRESAGE formulations varied from 2.2 times greater than that of water for the new formulations to 3.5 times greater than that of water for the original formulation. The mass attenuation coefficient for the three formulations is 12%-50% higher than the value for water. These differences occur over an energy range (10-100 keV) in which the photoelectric effect is the dominant interaction. The collision mass stopping powers of the relatively lower halogen-containing PRESAGE formulations also exhibit marginally better water equivalency than the original higher halogen-containing PRESAGE formulation. Furthermore, the depth dose curves for the lower halogen-containing PRESAGE formulations are slightly closer to that of water for a 6 MV beam. In the kilovoltage energy range, the depth dose curves for the lower halogen-containing PRESAGE formulations are in better agreement with water than the original PRESAGE formulation. CONCLUSIONS: Based on the results of this study, the new PRESAGE formulations with lower halogen content are more radiologically water equivalent overall than the original formulation. This indicates that the new PRESAGE formulations are better suited to clinical applications and are more accurate dosimeters and phantoms than the original PRESAGE formulation. While correction factors are still needed to convert the dose measured by the dosimeter to an absorbed dose in water in the kilovoltage energy range, these correction factors are considerably smaller for the new PRESAGE formulations compared to the original PRESAGE and the existing polymer gel dosimeters.

Direct dose to water dosimetry for pretreatment IMRT verification using a modified EPID.

PURPOSE: Electronic portal imaging devices (EPIDs) are high resolution systems that produce electronic dose maps with minimal time required for equipment setup, and therefore potentially present a time-saving alternative for intensity modulated radiation therapy (IMRT) pretreatment verification. A modified commercial EPID was investigated operated with an opaque sheet blocking the optical signal produced in the phosphor layer as a precursor to a switched mode dual dosimetry-imaging EPID system. The purpose of this study was to investigate the feasibility of using this system for direct dose to water dosimetry for pretreatment IMRT verification. METHODS: A Varian amorphous silicon EPID was modified by placing an opaque sheet between the Gd(2)S(2)O:Tb phosphor layer and the photodiode array to block the optical photons. The EPID was thus converted to a direct-detecting system (dEPID), in which the high energy radiation deposits energy directly in the photodiode array. The copper build-up was replaced with d(max) solid water. Sixty-one IMRT beams of varying complexity were delivered to the EPID, to EDR2 dosimetric film and to a 2D ion chamber array (MapCheck). EPID data was compared to film and MapCheck data using gamma analysis with 3%, 3mm pass criteria. RESULTS: The fraction of points that passed the gamma test was on average 98.1% and 98.6%, for the EPID versus film and EPID versus MapCheck comparisons, respectively. In the case of comparison with film, the majority of observed discrepancies were associated with problems related to film sensitivity or processing. CONCLUSIONS: The very close agreement between EPID and both film and MapCheck data demonstrates that the modified EPID is suitable for direct dose to water measurement for pretreatment IMRT verification. These results suggest a reconfigured EPID could be an efficient and accurate dosimeter. Alternatively, optical switching methods could be developed to produce a dual-mode EPID with both dosimetry and imaging capabilities.

The water equivalence of solid phantoms for low energy photon beams.

PURPOSE: To compare and evaluate the dosimetric water equivalence of several commonly used solid phantoms for low energy photon beams. METHODS: A total of ten different solid phantom materials was used in the study. The PENELOPE Monte Carlo code was used to calculate depth doses and beam profiles in all the phantom materials as well as the dose to a small water voxel at the surface of the solid phantom. These doses were compared to the corresponding doses calculated in a water phantom. The primary photon beams used ranged in energy from 50 to 280 kVp. RESULTS: A number of phantom materials had excellent agreement in dose compared to water for all the x-ray beam energies studied. RMI457 Solid Water, Virtual Water, PAGAT, A150, and Plastic Water DT all had depth doses that agreed with those in water to within 2%. For these same phantom materials, the dose changes in the water voxel at the surface of the solid phantom were within 2%, except for A150, which agreed to within 2.7%. By comparison, the largest differences in depth doses occurred for Plastic Water (-21.7%) and polystyrene (17.6%) for the 50 kVp energy photon beam and 8 cm diameter field size. Plastic Water gave the largest difference in the normalized beam profiles with differences of up to 3.5% as compared to water. Surface dose changes, due to the presence of the solid phantom acting as the backscatter material, were found to be up to 9.1% for polystyrene with significant differences also found for Plastic Water, PMMA, and RW3 phantoms. CONCLUSIONS: The following solid phantoms can be considered water equivalent and are recommended for relative dosimetry of low energy photon beams: A150, PAGAT, Plastic Water DT, RMI457 Solid Water, and Virtual Water. However, the following solid phantoms give significant differences, compared to water, in depth doses, profiles, and/or in surface doses due to backscatter changes: Plastic Water, PMMA, polystyrene, PRESAGE, and RW3.

An evaluation of ionization chambers for the relative dosimetry of kilovoltage x-ray beams.

In this work, the authors have evaluated ten different ionization chambers for the relative dosimetry of kilovoltage x-ray beams in the energy range of 50-280 kVp. Percentage depth doses in water and relative detector response (in Solid Water and in air) were measured for each of the x-ray beams studied using a number of chambers. Measured depth dose data were compared with Monte Carlo calculated depth doses using the EGSnrc Monte Carlo package and the BEAMnrc user code. The accuracy of the phase space files generated by BEAMnrc was verified by calculating the half-value layer and comparing with the measured half-value layer of each x-ray beam. The results indicate that the Advanced Markus, Markus, NACP, and Roos parallel plate ionization chambers were suitable for the measurement of depth dose data in this beam quality range with an uncertainty of less than 3%, including in the regions close to the water surface. While the relative detector response of the Farmer and scanning thimble chambers exhibited a better energy response, they were not suitable for depth dose measurements in the first 5 mm below the water surface with differences of up to 12% in the surface dose measurement for the 50 kVp x-ray beam. These differences were due to dose artifacts generated by the chamber size and the dose gradient. However, at depths greater than 5 mm, the Farmer and thimble scanning chambers gave uncertainties of less than 3% for the depth dose measurements for all beam energies. The PTW PinPoint 31006 chamber was found to give varying dose differences of up to 8% depending on the x-ray beam energy; this was attributed to the steel central electrode. The authors recommend that one of the parallel plate ionization chambers investigated be used to determine depth dose data for kilovoltage x-ray beams in the energy range studied and give correct dose information close to the surface and at depth in the water phantom.

EPID dosimetry: effect of different layers of materials on absorbed dose response.

PURPOSE: Commercial EPIDs are normally used in indirect detection mode (iEPID) where incident x-ray photons are converted to optical photons in a phosphor scintillator, which are then detected by a photodiode array. The EPIDs are constructed from a number of nonwater equivalent materials which affect the dose response of the detector. The so-called direct detection EPIDs (dEPIDs), operating without the phosphor layer, have been reported to display dose response close to in-water data. In this study, the effect that different layers of materials in the EPID have on the dose response was experimentally investigated and evaluated with respect to changes in field size response and beam profiles. METHODS: An iEPID was disassembled and the different layers of materials were removed or replaced with other materials. Data were also obtained on and off the support arm and with a sheet of opaque paper blocking the optical photons from the gadolinium oxysulfide (Gd2S2O:Tb) phosphor layer. Field size response was measured for field sizes ranging from 2 x 2 to 25 x 25 cm2, and profiles for the 25 x 25 cm2 beams were extracted from the data. RESULTS: The iEPID configuration was found to be very sensitive to backscatter. The increases in output with solid water backscatter compared to the no backscatter case were 14.7% and 6.6% at the largest field size investigated for the 6 and 18 MV beams, respectively. The Gd2S2O:Tb phosphor layer had a large influence on field size response as well as beam profiles for 6 MV photons, while no major effects were observed for the 18 MV beam. For 18 MV large differences in dose response were found when the standard 1 mm Cu buildup was changed for dmax equivalent Cu or solid water buildup, indicating that head scatter largely influences dose response for this energy. When the optical photons originating in the Gd2S2O:Tb layer were blocked from reaching the photodiodes, both field size output data and beam profiles corresponded well with data obtained in the dEPID configuration as well as reference ion chamber data for both energies. CONCLUSIONS: As expected, changing the layers of material in the EPID had a dramatic effect on dose response, which was often quite complex. For 6 MV, the complex dose response is mainly caused by the optical photons from the Gd2S2O:Tb layer, while insufficient filtering of scattered radiation largely affects the dose response for the 18 MV beam. The iEPID was also found to be very sensitive to backscatter for both energies. Blocking the optical photons created in the Gd2S2O:Tb layer essentially changed the iEPID configuration into the dEPID configuration, thus demonstrating great potential for a system that can be optimized for both imaging and dosimetry.

Predicting the clonogenic survival of A549 cells after modulated x-ray irradiation using the linear quadratic model.

In this study we present two prediction methods, mean dose and summed dose, for predicting the number of A549 cells that will survive after modulated x-ray irradiation. The prediction methods incorporate the dose profile from the modulated x-ray fluence map applied across the cell sample and the linear quadratic (LQ) model. We investigated the clonogenic survival of A549 cells when irradiated using two different modulated x-ray fluence maps. Differences between the measured and predicted surviving fraction were observed for modulated x-ray irradiation. When the x-ray fluence map produced a steep dose gradient across the sample, fewer cells survived in the unirradiated region than expected. When the x-ray fluence map produced a less steep dose gradient across the sample, more cells survived in the unirradiated region than expected. Regardless of the steepness of the dose gradient, more cells survived in the irradiated region than expected for the reference dose range of 1-10 Gy. The change in the cell survival for the unirradiated regions of the two different dose gradients may be an important factor to consider when predicting the number of cells that will survive at the edge of modulated x-ray fields. This investigation provides an improved method of predicting cell survival for modulated x-ray radiation treatment. It highlights the limitations of the LQ model, particularly in its ability to describe the biological response of cells irradiated under these conditions.

Modelling optical scattering artefacts for varying pathlength in a gel dosimeter phantom.

A gelatin phantom containing an optically scattering funnel-shaped region of elevated optical density (OD) was used to examine light-scattering-induced artefacts in a cone-beam optical CT scanner used for gel dosimetry. To simulate polymer gel dosimeters, the opacity was introduced by adding a colloidal scatterer to the gelatin. Scatter results in an underestimate of OD (hence dose). In line profiles of OD taken from 3D reconstructions of the funnel, those profiles with a long pathlength through high OD regions exhibited a 'dishing' (or 'cupping') artefact, while those of short pathlength exhibited the opposite effect-'doming'. These phenomena are accounted for by a model that includes the effect of stray, scattered light.

Light-scattering-induced artifacts in a complex polymer gel dosimetry phantom.

Certain polymer gels become turbid on exposure to ionizing radiation, a property exploited in medical dosimetry to produce three-dimensional dose maps for radiotherapy. These maps can be read using optical computed tomography (CT). A test phantom of complex shape ("layered tube") was developed to investigate the optical properties of polymer gel dosimeters when read using optical CT. Extinction coefficient profiles from tomographically reconstructed slices of the phantom exhibited several artifacts. A simple model invoking scattered light in the gel was able to account for all artifacts, which in a real dosimeter may have been mistaken for other phenomena, resulting in incorrect readings of dose.

Initial evaluation of a commercial EPID modified to a novel direct-detection configuration for radiotherapy dosimetry.

Electronic portal imaging devices (EPIDs) integrated with medical linear accelerators utilize an indirect-detection EPID configuration (ID-EPID). Amorphous silicon ID-EPIDs provide high quality low dose images for verification of radiotherapy treatments but they have limitations as dosimeters. The standard ID-EPID configuration includes a high atomic number phosphor scintillator screen, a 1 mm copper layer, and other nonwater equivalent materials covering the detector. This configuration leads to marked differences in the response of an ID-EPID compared to standard radiotherapy dosimeters such as ion chambers in water. In this study the phosphor and copper were removed from a standard commercial EPID to modify the configuration to a direct-detection EPID (DD-EPID). Using solid water as the buildup and backscatter for the detector, dosimetric measurements were performed on the DD-EPID and compared to standard dose-in-water data for 6 and 18 MV photons. The sensitivity of the DD-EPID was approximately eight times less than the ID-EPID but the signal was sufficient to produce accurate and reproducible beam profile measurements for open beams and an intensity-modulated beam. Due to the lower signal levels it was found necessary to ensure that the dark field correction (no radiation) DD-EPID signal was stable or updated frequently. The linearity of dose response was comparable to the ID-EPID but with a greater under-response at low doses. DD-EPID measurements of field size output factors and beam profiles at the depth of maximum dose (dmax), and tissue-maximum ratios between the depths of 0.5 and 10 cm, were in close agreement with dose in water measurements. At depths beyond dmax the DD-EPID showed a greater change in response to field size than ionisation chamber measurements and the beam penumbrae were broader compared to diode scans. The modified DD-EPID configuration studied here has the potential to improve the performance of EPIDs for dose verification of radiotherapy treatments.

The impact of MLC transmitted radiation on EPID dosimetry for dynamic MLC beams.

The purpose of this study was to experimentally quantify the change in response of an amorphous silicon (a-Si) electronic portal imaging device (EPID) to dynamic multileaf collimator (dMLC) beams with varying MLC-transmitted dose components and incorporate the response into a commercial treatment planning system (TPS) EPID prediction model. A combination of uniform intensity dMLC beams and static beams were designed to quantify the effect of MLC transmission on EPID response at the central axis of 10 x 10 cm2 beams, at off-axis positions using wide dMLC beam profiles, and at different field sizes. The EPID response to MLC transmitted radiation was 0.79 +/- 0.02 of the response to open beam radiation at the central axis of a 10 x 10 cm2 field. The EPID response to MLC transmitted radiation was further reduced relative to the open beam response with off-axis distance. The EPID response was more sensitive to field size changes for MLC transmitted radiation compared to open beam radiation by a factor of up to 1.17 at large field sizes. The results were used to create EPID response correction factors as a function of the fraction of MLC transmitted radiation, off-axis distance, and field size. Software was developed to apply the correction factors to each pixel in the TPS predicted EPID image. The corrected images agreed more closely with the measured EPID images in areas of intensity modulated fields with a large fraction of MLC transmission and, as a result the accuracy of portal dosimetry with a-Si EPIDs can be improved. Further investigation into the detector response function and the radiation source model are required to achieve improvements in accuracy for the general case.

Quantitative SPECT reconstruction using CT-derived corrections.

A method for achieving quantitative single-photon emission computed tomography (SPECT) based upon corrections derived from x-ray computed tomography (CT) data is presented. A CT-derived attenuation map is used to perform transmission-dependent scatter correction (TDSC) in conjunction with non-uniform attenuation correction. The original CT data are also utilized to correct for partial volume effects in small volumes of interest. The accuracy of the quantitative technique has been evaluated with phantom experiments and clinical lung ventilation/perfusion SPECT/CT studies. A comparison of calculated values with the known total activities and concentrations in a mixed-material cylindrical phantom, and in liver and cardiac inserts within an anthropomorphic torso phantom, produced accurate results. The total activity in corrected ventilation-subtracted perfusion images was compared to the calibrated injected dose of [(99m)Tc]-MAA (macro-aggregated albumin). The average difference over 12 studies between the known and calculated activities was found to be -1%, with a range of +/-7%.

Benchmarking of a motion sensing system for medical imaging and radiotherapy.

We have tested the performance of an Optotrak Certus system, which optically tracks multiple markers, in both position and time. To do this, we have developed custom code which enables a range of testing protocols, and make this code available to the community. We find that the Certus' positional accuracy is very high, around 20 microm at a distance of 2.8 m. In contrast, we find that its timing accuracy is typically no better than around 5-10% for typical data rates, whether one is using an ethernet connection or a dedicated SCSI link from the system to a host computer. However, with our code we are able to attach very accurate timestamps to the data frames, and in cases where regularly-spaced data are not an absolute requirement, this will be more than adequate.

Investigation of the relationship between linear attenuation coefficients and CT Hounsfield units using radionuclides for SPECT.

This study has investigated the relationship between linear attenuation coefficients (mu) and Hounsfield units (HUs) for six materials covering the range of values found clinically. Narrow-beam mu values were measured by performing radionuclide transmission scans using (99m)Tc, (123)I, (131)I, (201)Tl and (111)In. The mu values were compared to published data. The relationships between mu and HU were determined. These relationships can be used to convert computed tomography (CT) images to mu-maps for single photon emission computed tomography (SPECT) attenuation correction.