Change In Dose Response Research Articles

Dosimetry in MRgPT: Impact of magnetic fields on TLD dose response during proton irradiation.

Proton beam therapy, when integrated with MRI guidance, presents complex dosimetric challenges due to interactions with magnetic fields. Prior research has emphasized the nuanced impact of magnetic fields on dosimetry. For thermoluminescent dosimeters (TLDs) the electron-return effect, alongside small air cavities surrounding the pellets, can lead to nonuniform dose distributions. Future MR-guided proton therapy will require reliable methods for end-to-end tests and dosimetric audits, which so far are often performed using TLDs equipped with phantoms. This implicates the necessity of accounting for theseinteractions. This study investigates the influence of magnetic fields on TLDs at two proton energies, using magnetic field strengths of 0, 0.25, and , aiming to clarify their impact on dose measurementaccuracy. The study was conducted at a synchrotron-based ion beam therapy beam line, enhanced by a resistive dipole magnet for creating magnetic fields up to to simulate MR-guided proton therapy. Individual correction factors were applied for TLD measurements. The impact of air gaps on the TLD signal was evaluated using three dedicated TLD holders with air gaps of 0.1, 0.25, and 0.5 mm surrounding the TLD pellets using the highest available proton energy of . Additionally, the influence of the magnetic field strength on the TLD response was evaluated for two proton energies of and . The study found no statistically significant variation in TLD dose response attributable to changes in the air gap or the presence of magnetic fields. A power analysis indicated an upper limit on a potential change in dose-response as small as 1.5%. The findings suggested that the impact of air gap variations and magnetic field strengths on the TLD response was below the detection threshold of TLD sensitivity. This emphasizes the suitability of TLDs for dose measurement in MR-guided proton therapy, indicating that additional correction factors may not be necessary despite the influence of magneticfields.

SU‐F‐J‐147: Magnetic Field Dose Response Considerations for a Linac Monitor Chamber

Purpose:The impact of magnetic fields on the readings of a linac monitor chamber have not yet been investigated. Herein we examine the total dose response as well as any deviations in the beam parameters of flatness and symmetry when a Varian monitor chamber is irradiated within an applied magnetic field. This work has direct application to the development of Linac‐MR systems worldwide.Methods:A Varian monitor chamber was modeled in the Monte Carlo code PENELOPE and irradiated in the presence of a magnetic field with a phase space generated from a model of a Linac‐MR prototype system. The magnetic field strength was stepped from 0 to 3.0T in both parallel and perpendicular directions with respect to the normal surface of the phase space. Dose to each of the four regions in the monitor chamber were scored separately for every magnetic field adaptation to evaluate the effect of the magnetic field on flatness and symmetry.Results:When the magnetic field is perpendicular to the phase space normal we see a change in dose response with a maximal deviation (10–25% depending on the chamber region) near 0.75T. In the direction of electron deflection we expectedly see opposite responses in chamber regions leading to a measured asymmetry. With a magnetic field parallel to the phase space normal we see no measured asymmetries, however there is a monotonic rise in dose response leveling off at about +12% near 2.5T.Conclusion:Attention must be given to correct for the strength and direction of the magnetic field at the location of the linac monitor chamber in hybrid Linac‐MR devices. Elsewise the dose sampled by these chambers may not represent the actual dose expected at isocentre; additionally there may be a need to correct for the symmetry of the beam recorded by the monitor chamber.Fallone is a co‐founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi‐planar linac MR for commercialization).

Dosimetric Characteristics of a Two-Dimensional Diode Array Detector Irradiated with Passively Scattered Proton Beams

Purpose: To evaluate the dosimetric characteristics of a two-dimensional (2D) diode array detector irradiated with passively scattered proton beams. Materials and Methods: A diode array detector, MapCHECK (Model 1175, Sun Nuclear, Melbourne, FL, USA) was characterized in passive-scattered proton beams. The relative sensitivity of the diodes and absolute dose calibration were determined using a 250 MeV beam. The pristine Bragg curves (PBCs) measured by MapCHECK diodes were compared with those of an ion chamber using a range shift method. The water-equivalent thickness (WET) of the diode array detector’s intrinsic buildup also was determined. The inverse square dependence, linearity, and other proton dosimetric quantities measured by MapCHECK were also compared with those of the ion chambers. The change in the absolute dose response of the MapCHECK as a function of accumulated radiation dose was used as an indicator of radiation damage to the diodes. 2D dose distribution with and without the compensator were measured and compared with the treatment planning system (TPS) calculations. Results: The WET of the MapCHECK diode’s buildup was determined to be 1.7 cm. The MapCHECK-measured PBC were virtually identical to those measured by a parallel-plate ion chamber for 160, 180, and 250 MeV proton beams. The inverse square results of the MapCHECK were within ±0.4% of the ion chamber results. The linearity of MapCHECK results was within 1% of those from the ion chamber as measured in the range between 10 and 300 MU. All other dosimetric quantities were within 1.3% of the ion chamber results. The 2D dose distributions for non-clinical fields without compensator and the patient treatment fields with the compensator were consistent with the TPS results. The absolute dose response of the MapCHECK was changed by 7.4% after an accumulated dose increased by 170 Gy. Conclusions: The MapCHECK is a convenient and useful tool for 2D dose distribution measurements using passively scattered proton beams. Variations in MapCHECK’s dose response with increasing levels of total accumulated radiation dose should be carefully monitored.

Temperature and temporal dependence of the optical response for a radiochromic dosimeter

Both temporal and thermal dependencies of the dose response have been observed in radiochromic dosimeters. As these dependencies may be influenced by the dose level, the present study investigates the temperature dependence during irradiation and the temporal change of the optical response following irradiation of radiochromic dosimeters at a range of doses. Cuvette samples of the PRESAGE™ radiochromic dosimeter were irradiated within a dose range of 0-10 Gy at irradiation temperatures within 5-35 °C and postirradiation storage within 6-30 °C. The optical response due to irradiation was measured using a standard spectrophotometer and the data were analyzed in terms of thermal and temporal change. The initial dose response was linear over the applied dose range independent of irradiation temperature. However, the optical response to a specific dose increased exponentially with irradiation temperature corresponding to an activation energy of 0.114 ± 0.007 eV. The temporal change in dose response after irradiation consisted of an offset, an auto-oxidation rate with activation energy 0.84 ± 0.03 eV, and an initial exponential increase in optical response (1.6 ± 0.2 eV) followed by an exponential decrease in optical response (0.98 ± 0.08 eV). These contributions depended on both storage temperature and the dose given, leading to a nonlinear dose response with time at low storage temperatures and a high auto-oxidation rate at high storage temperatures. Thermal equilibration is important to the radiochromic dosimeter investigated due to an exponential change in dose response with irradiation temperature and a considerable postirradiation temporal change in response. For the dosimeter version investigated in this study, a compromise in storage temperature has to be made between increasing the nonlinearity of the dose response with time and inducing a high auto-oxidation rate.

Temperature dependence of the dose response for a solid-state radiochromic dosimeter during irradiation and storage

The dose response of radiochromic dosimeters is based on radiation-induced chemical reactions and is thus likely to be thermally influenced. In this study we have therefore investigated the temperature dependence of the dose response for such dosimeters, regarding both irradiation and storage conditions. Dosimeter samples in cuvettes were irradiated to 5 Gy. The temperature for the different cuvettes during irradiation and post-irradiation storage was varied in the range of 3-30 degrees C in order to quantify the temperature dependence of the dosimeter response. The optical properties of the dosimeter samples were measured using a spectrophotometer before irradiation as well as at several times after irradiation to quantify the temporal variation of dose response (expressed as the optical density change induced by irradiation) as a function of storage temperature. The measurements show considerable temperature dependencies of dose response both during irradiation and storage. Fit to an Arrhenius equation revealed an activation energy of 1.4 +/- 0.2 eV for the variation in irradiation temperature, indicating a contribution from a thermally activated process. Variation in dose response at different storage temperatures showed an exponential increase with time followed by a decrease in optical density. Exponential Arrhenius fits to rate constants gave activation energies of 1.7 +/- 0.2 eV for the increase in dose response and 2.3 +/- 0.5 eV for the subsequent decrease, in this case dominated by thermally activated processes. Due to the exponential dependencies, stabilization of the dosimeter during irradiation at low temperatures (e.g., 5 degrees C) is preferable in clinical use to optimize the accuracy of the dose response. In addition, a low storage temperature is recommended in order to minimize the post-irradiation temporal change in dose response and thereby increase the post-irradiation stability of the dosimeter. The measurements in this study show that if the observed temperature and temporal dependencies are not considered, this could potentially deteriorate the accuracy of the dosimeter.

Identification of Protein Domains That Control Proton and Calcium Sensitivity of ASIC1a

The acid-sensing ion channels (ASICs) open in response to extracellular acidic pH, and individual subunits display differential sensitivity to protons and calcium. ASIC1a acts as a high affinity proton sensor, whereas ASIC2a requires substantially greater proton concentrations to activate. Using chimeras composed of ASIC1a and ASIC2a, we determined that two regions of the extracellular domain (residues 87-197 and 323-431) specify the high affinity proton response of ASIC1a. These two regions appear to undergo intersubunit interactions within the multimeric channel to specify proton sensitivity. Single amino acid mutations revealed that amino acids around Asp(357) play a prominent role in determining the pH dose response of ASIC1a. Within the same region, mutation F352L abolished PcTx1 modulation of ASIC1a. Surprisingly, we determined that another area of the extracellular domain was required for calcium-dependent regulation of ASIC1a activation, and this region functioned independently of high affinity proton sensing. These results indicate that specific regions play overlapping roles in pH-dependent gating and PcTx1-dependent modulation of ASIC1a activity, whereas a distinct region determines the calcium dependence of ASIC1a activation.

High-density lipoprotein cholesterol and triglyceride response with simvastatin versus atorvastatin in familial hypercholesterolemia

The clinical and biochemical determinants of high-density lipoprotein (HDL) and triglyceride response to simvastatin and atorvastatin were assessed in 150 patients with severe hyperlipidemia treated in a randomized open-trial format design. Triglyceride reduction was only dependent on HDL:apolipoprotein A1, change in apolipoprotein B, and dose response, whereas an increase in HDL was dependent on initial LDL, change in LDL or dose response, and therapy with simvastatin.

Protein Phosphatase 2A Plays a Role in the Suckling-Induced Changes in the Responsiveness of Pituitary Mammotropes

It is well established that PRL secretion is under a tonic inhibition exercised by the hypothalamic dopamine (DA). One feature of this regulation is an immediate withdrawal reaction (elevation of PRL release) of mammotropes after disruption of hypothalamic influence. Although plasma PRL rises rapidly, the suckling stimulus does not cause an acute diminution of hypothalamic DA, but, as we have previously demonstrated, it results in an almost immediate (within 10 min) desensitization of mammotropes as indicated by the change in dose response of DA to inhibit PRL release. Our present investigations relate to the phenomenon of this change in responsiveness of PRL cells. This was accomplished by using the reverse hemolytic plaque assay to evaluate the secretory characteristics of individual PRL secretors derived from lactating rats either before or after a 10-min suckling stimulus. To investigate the mechanism of these changes, the binding characteristics of [3H]spiperone on pituitary membranes from nonsuckled and suckled rats have been compared, and the possible involvement of dephosphorylating enzymes was tested by using okadaic acid (OA) in a dose of 2 nm that preferentially and selectively inhibits protein phosphatase-2A (PP2A) activity. We have also determined the activities of PP1 and PP2A in pituitary tissue samples as well as in enzymatically dispersed cells. Mammotropes from nonsuckled rats exhibited a depression of PRL release after both DA and OA treatment and an elevation after withdrawal of DA. This suggests that the secretory response of mammotropes obtained from nonsuckled rats still shows those two responses that are characteristic of the tonic inhibitory regulation. In contrast, superimposition of suckling in vivo or application of OA together with DA pretreatment in cells from nonsuckled rats in vitro resulted in a disappearance of the dissociation-induced elevation of PRL release, indicating an abolishment of the tonic inhibitory action of DA. Evidence is also presented that the PP2A, but not the PP1, activity of the anterior lobe is significantly lower after a 10-min suckling stimulus. Moreover, DA is able to decrease PP2A activity in dispersed pituitary cells obtained from nonsuckled, but not from suckled, animals. In contrast, there were no differences in either the affinity or the number of binding sites between nonsuckled and suckled rats. Taken together, our results suggest that the suckling-induced decrease in PP2A activity plays a role in the uncoupling of D2 receptors on mammotropes from the tonic inhibitory signaling pathway.

Protein phosphatase 2A plays a role in the suckling-induced changes in the responsiveness of pituitary mammotropes.

It is well established that PRL secretion is under a tonic inhibition exercised by the hypothalamic dopamine (DA). One feature of this regulation is an immediate withdrawal reaction (elevation of PRL release) of mammotropes after disruption of hypothalamic influence. Although plasma PRL rises rapidly, the suckling stimulus does not cause an acute diminution of hypothalamic DA, but, as we have previously demonstrated, it results in an almost immediate (within 10 min) desensitization of mammotropes as indicated by the change in dose response of DA to inhibit PRL release. Our present investigations relate to the phenomenon of this change in responsiveness of PRL cells. This was accomplished by using the reverse hemolytic plaque assay to evaluate the secretory characteristics of individual PRL secretors derived from lactating rats either before or after a 10-min suckling stimulus. To investigate the mechanism of these changes, the binding characteristics of [3H]spiperone on pituitary membranes from nonsuckled and suckled rats have been compared, and the possible involvement of dephosphorylating enzymes was tested by using okadaic acid (OA) in a dose of 2 nM that preferentially and selectively inhibits protein phosphatase-2A (PP2A) activity. We have also determined the activities of PP1 and PP2A in pituitary tissue samples as well as in enzymatically dispersed cells. Mammotropes from nonsuckled rats exhibited a depression of PRL release after both DA and OA treatment and an elevation after withdrawal of DA. This suggests that the secretory response of mammotropes obtained from nonsuckled rats still shows those two responses that are characteristic of the tonic inhibitory regulation. In contrast, superimposition of suckling in vivo or application of OA together with DA pretreatment in cells from nonsuckled rats in vitro resulted in a disappearance of the dissociation-induced elevation of PRL release, indicating an abolishment of the tonic inhibitory action of DA. Evidence is also presented that the PP2A, but not the PP1, activity of the anterior lobe is significantly lower after a 10-min suckling stimulus. Moreover, DA is able to decrease PP2A activity in dispersed pituitary cells obtained from nonsuckled, but not from suckled, animals. In contrast, there were no differences in either the affinity or the number of binding sites between nonsuckled and suckled rats. Taken together, our results suggest that the suckling-induced decrease in PP2A activity plays a role in the uncoupling of D2 receptors on mammotropes from the tonic inhibitory signaling pathway.