The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

[Preparation and roles of sliver-loaded viscous hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice].

Objective: To prepare the modified hyaluronic acid viscous hydrogel loaded with sliver particles and to explore the roles and mechanism of the hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice. Methods: The experimental research method was adopted. Dopamine modified hyaluronic acid (HA-DA) and phenylboric acid modified hyaluronic acid (HA-PBA) were prepared, and their characteristic peaks were detected by Fourier-transform infrared spectroscopy. Different mass of acrylamides was added to HA-DA and HA-PBA to prepare the viscous hydrogel with mass fraction of acrylamide in 10%, 15%, and 20%. The gelation of the viscous hydrogel with mass fraction of acrylamide in 20% was observed in the state of tilt and inversion at 37 ℃, and the storage modulus and loss modulus of the above 3 kinds of viscous hydrogels were detected by rotational rheometer. The sliver-loaded viscous hydrogel was prepared by adding nano silver ions to the viscous hydrogel with mass fraction of acrylamide in 20%. The concentration of silver ions released by sliver-loaded viscous hydrogel was measured by inductively coupled plasma mass spectrometer, and the cumulative release rate of silver ion was calculated (n=5). The mouse fibroblasts L929 were divided into phosphate buffered saline (PBS) group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, and the cell survival was detected by cell counting kit 8 method after 1, 2, and 3 d of culture (n=5). Twenty-four male C57BL/6 mice aged 6-8 weeks were selected, and forty-eight full-thickness skin defect wounds were inflicted and inoculated with the mixture of Escherichia coli and Staphylococcus aureus in the back of the mice, with two wounds in each mouse. The wounds were divided into normal saline group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, with 16 wounds in each group, and two wounds in each mouse were divided into different groups. On post injury day (PID) 3, 7, 10, and 14, the wound healing was observed and the wound healing rate was calculated. On PID 3, the colony forming units of Escherichia coli and Staphylococcus aureus in wounds were observed and counted. On PID 14, the epithelized epidermal thickness and the optical density of collagen fiber in wounds were observed and analyzed after hematoxylin eosin staining and Masson staining, respectively. On PID 3, 7, and 10, the expressions of tumor necrosis factor α (TNF-α), transforming growth factor ß1 (TGF-ß1), and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. The number of wounds in each index detecting at each time point was four. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni correction. Results: The characteristic peaks of HA-PBA were detected at the wave numbers of 1 369 and 1 425 cm-1, indicating that phenylboric acid had been successfully grafted on hyaluronic acid, and the characteristic peaks of HA-DA were detected at the wave numbers of 1 516 and 1 431 cm-1, indicating that dopamine had been successfully grafted on hyaluronic acid. The viscous hydrogel with mass fraction of acrylamide in 20% maintained the stable and no-flow condition of gelation in the state of tilt and inversion at 37 ℃. The storage modulus and loss modulus of the viscous hydrogel increased with the increase of acrylamide content, the storage modulus and loss modulus of the 3 kinds of viscous hydrogels had no obvious changes with the increase of the oscillation frequency or time, and the storage modulus of the 3 kinds of acrylamide hydrogels were greater than the loss modulus. The release of silver ion in the sliver-loaded viscous hydrogel lasted for 7 days, and the cumulative release rate of silver ion was up to 65%. After 1, 2, and 3 d of culture, the cell survival rates in sliver-loaded viscous hydrogel group were significantly lower than those in PBS group and viscous hydrogel group (P<0.05 or P<0.01), while after 1 d of culture, the cell survival rate in viscous hydrogel group was significantly lower than that in PBS group (P<0.01). With extension of time after injury, the wounds of mice in the 3 groups shrank gradually. On PID 3, 7, 10, and 14, the wound healing rates in sliver-loaded viscous hydrogel group were (53.0±3.6)%, (75.3±6.9)%, (93.3±1.2)%, and (96.7±0.8)%, which were significantly higher than (21.8±6.4)%, (53.9±8.2)%, (72.0±7.8)%, and (92.5±0.4)% in normal saline group (P<0.01). On PID 3 and 14, the wound healing rates in sliver-loaded viscous hydrogel group were significantly higher than (43.5±2.4)% and (94.1±1.5)% in viscous hydrogel group (P<0.05). On PID 3 and 10, the wound healing rates in viscous hydrogel group were significantly higher than those in normal saline group (P<0.01). On PID 3, the colony forming units of two bacteria in wound of sliver-loaded viscous hydrogel group were significantly less than those in normal saline group and viscous hydrogel group (P<0.01), while the colony forming units of two bacteria in wound of viscous hydrogel group were significantly less than those in normal saline group (P<0.05). On PID 14, the wounds were basically epithelialized and the epidermis was thicker, with collagen protein content being increased significantly and more orderly arranged collagen in sliver-loaded viscous hydrogel group compared with those in the other 2 groups. On PID 14, the epidermal thickness in wounds of sliver-loaded viscous hydrogel group was significantly increased compared with that in the other two groups (P<0.05), and the optical density of collagen fiber was significantly increased compared with those in normal saline group (P<0.05). On PID 3, the expressions of TGF-ß1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group (P<0.05 or P<0.01), while the expression of VEGF in wounds of viscous hydrogel group was significantly higher than that in normal saline group (P<0.01). On PID 7, the expression of TGF-ß1 in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in the other 2 groups (P<0.01), and the expression of VEGF was significantly higher than that in normal saline group (P<0.01). On PID 10, the expression of TNF-α in wounds of sliver-loaded viscous hydrogel group was significantly lower than that in normal saline group (P<0.05), the expressions of TGF-ß1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group (P<0.05 or P<0.01), and the expression of VEGF in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in viscous hydrogel group (P<0.05). Conclusions: The sliver-loaded viscous hydrogel prepared in this study has good stability and elasticity, which can continuously release silver ions and help to accelerate the healing of full-thickness defect wounds with bacterial colonization in mice. Besides, the sliver-loaded viscous hydrogel has low biological toxicity and can promote re-epithelialization, collagen deposition as well as angiogenesis of wounds, which may be related to the infiltration and regression of inflammatory cells.

[Effectiveness evaluation of health belief model-based health education intervention for patients with hypertension in community settings].

Objective: To evaluate the effectiveness of health belief model-based health education intervention in improving blood pressure control of patients with hypertension in community settings. Methods: From September 2016 to September 2017, 400 newly diagnosed patients with hypertension were recruited from 6 community healthcare centers with comparable population size and health services in the Shunyi District of Beijing. All community healthcare centers were randomly assigned to the intervention group (206 patients) and the control group (194 patients). Patients in the intervention group received 3 lectures (20-30 min for each) of health belief model-based health education. Patients in the control group received usual care. The basic characteristics, health beliefs, and health literacy were collected, and blood pressure was measured before and after the intervention, respectively. The difference-in-difference model was used to analyze the change of blood pressure and the influencing factors between two groups before and after the intervention. Results: A total of 134 patients in the intervention group and 129 patients in the control group completed the study. After adjusting for the age, gender, family income, medical insurance, chronic diseases and family history, the score of perceived barriers was increased by 1.65 (P=0.016), and perceived seriousness was decreased by 0.73 (P=0.018). The systolic blood pressure of patients was decreased by 7.37 mmHg (1 mmHg=0.133 kPa, P=0.001) and diastolic blood pressure was decreased by 4.07 mmHg (P=0.014), respectively. The ß (95%CI) values were -7.37 (-11.88,-2.86) and -4.07 (-7.30, -0.84). The perceived susceptibility and self-efficacy had a significant influence on the blood pressure of patients (P<0.05). Conclusion: Health belief model-based health education intervention could significantly improve the blood pressure control of patients with hypertension in the community settings.

[Advances in immune checkpoint inhibitors in gastrointestinal cancer].

Currently, immunotherapy is considered as the fourth major modality of cancer treatment except surgery, chemotherapy and radiotherapy. The new therapeutic approach based on immune checkpoint inhibitors is a landmark innovation. Strategies considering checkpoint inhibitors have shown good anti-tumor effect by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1). Moreover, DNA mismatch repair-deficient tumors appear to be potential candidates for these therapies. This review summarizes the discussion and oral presentations in the annual meeting of American Society of Clinical Oncology (ASCO) and ASCO-gastrointestinal cancer (GI) in 2016 and provides an update on immunotherapy in gastrointestinal cancers.

Crystallization of Lennard-Jones liquids under dynamic compression: Heterogeneous and homogeneous nucleation.

We investigate crystallization of Lennard-Jones liquids on substrates under dynamic compression with large-scale molecular dynamics simulations. The substrates examined include single crystals and bicrystals with different crystallographic orientations, and the loading paths include shock and quasi-isentropic loading. Microstructure is characterized with simulated x-ray diffraction and orientation mapping. For shock loading, only heterogeneous nucleation occurs at the simulation scales. Quasi-isentropic loading induces less heating and larger supercooling; as a result, heterogeneous nucleation occurs at low loading strengths, and both heterogeneous and homogeneous nucleation occur at high loading strengths, despite the crystalline substrates. Crystallization depends on the substrate structure (crystal orientation and grain boundary) and loading characteristics. Deformation may induce grain structure change (e.g., reorientation and twinning) of substrates and affect subsequent crystallization. Crystallization rate is anisotropic, inversely proportional to the cosine of the dihedral angle between the substrate plane and a main {111} growth plane.

Methylation analysis of CXCR1 in mammary gland tissue of cows with mastitis induced by Staphylococcus aureus.

Mastitis is the most important disease in the global dairy industry, and causes large economic losses. Staphylococcus aureus is one of most common pathogens that cause bovine mastitis. CXCR1 has been implicated as a prospective genetic marker for mastitis resistance in dairy cows; CXCR1 expression significantly increases when cows have mastitis. To investigate the mechanisms involved in its increased expression, bisulfite sequencing polymerase chain reaction (PCR) was used to detect the methylation status of CXCR1 CpG island, and quantitative fluorescence PCR was used to detect CXCR1 expression in bovine mammary tissue induced with S. aureus in three Chinese Holstein cows. No CpG island was found for bovine CXCR1 in the upstream 2-kb region, whereas one CpG island that contained 13 CpG sites was found in exon 1 of CXCR1. All of the CpG sites were under hypermethylation from 90 to 100% in the mammary tissues. When the mammary gland mRNA expression of CXCR1 was 12.10-fold higher in infected cow quarters than in uninfected quarters, the methylation levels of the CpG site at position 519 were significantly lower in the infected quarters than in the uninfected quarters. Pearson correlation analysis showed that the methylation level at position 519 was significantly negatively correlated with the CXCR1 mRNA expression level (P < 0.05). These results indicate that the methylation of the CpG site at position 519 may regulate CXCR1 expression in cows with mastitis induced by S. aureus, but further studies are needed to elucidate the mechanisms involved.

Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system.

PURPOSE: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). METHODS: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm(2)/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. RESULTS: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. CONCLUSIONS: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future.

Magnetic resonance imaging retinal oximetry: a quantitative physiological biomarker for early diabetic retinopathy?

AIMS: To assess the efficacy of using magnetic resonance imaging measurements of retinal oxygenation response to detect early diabetic retinopathy in patients with Type 2 diabetes. METHODS: Magnetic resonance imaging was conducted during 100% oxygen inhalation in patients with Type 2 diabetes with either no diabetic retinopathy (n = 12) or mild to moderate background diabetic retinopathy (n = 12), as well as in healthy control subjects (n = 12). Meanwhile, changes in retinal oxygenation response were measured. RESULTS: In the healthy control group, levels of retinal oxygenation response increased slowly during 100% oxygen inhalation. In contrast, they increased more quickly and attained homeostasis much earlier in the groups with background diabetic retinopathy (at the 20-min time point) and with no diabetic retinopathy (at the 25-min time point) than in the healthy control group (at the 42-min time point). Furthermore, levels of retinal oxygenation response in the group with background diabetic retinopathy increased more than that of the group with no diabetic retinopathy, which in turn increased more than that of the healthy control group. There are statistically significant differences between the group with background diabetic retinopathy and the healthy control group at 6-, 8-, 10-, 15-, 20- and 25-min time points (P < 0.05). According to the normal range of the healthy control group by setting fundus photography results as 'gold standard' in our research, the sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic area for reporting the early indications of utility of diabetic retinopathy were 83.33%, 58.33%, 50%, 87.5% and 0.774, respectively. CONCLUSIONS: The results indicate that magnetic resonance imaging is a potential screening method and probably a quantitative physiological biomarker to find early diabetic retinopathy in patients with Type 2 diabetes.

SU-D-BRCD-01: Evaluation of Zebra Multi-Layer Ionization Chamber System for Patient Treatment Field and Machine QA for Spot Scanning and Passive Scattering Proton Beams.

PURPOSE: To evaluate Zebra multi-layer ionization chamber system for patient treatment field and machine QA for spot scanning proton beams (SSPB) and passive scattering proton beams (PSPB). METHODS: Zebra dose measurement system (IBA Dosimetry), consisting of 180 parallel platechambers with 2 mm detector spacing, was used for measuring proton beamdepth dose curves (DDC) for spread out Bragg peaks (SOBP) and single spot pristine Bragg peaks (PBP). The measurements were performed for 100 to 250 MeV PSPB and 89.2 to 221.8 MeV SSPB using the Hitachi ProBeat synchrotron based delivery system. An in-house Matlab based analysis software was used to compare the Zebra measured DDC with those measured by the Markus chamber in a PTW water tank (MC-WT). Several verification plans in the water phantom were created for patient treatment fields using the Eclipse treatment planning system (TPS). The DDC for individual verification fields were measured using the Zebra andcomparisons were made with the TPS calculations. RESULTS: The dosedifferences between the Zebra and MC-WT measurements in the plateau regions of the DDC are within 2% for various energies of PSPB, but are larger than 2% at the sharp dose distal gradient regions. The values for distal penumbra widths, range and SOBP widths from Zebra and MC-WT measurements agree within 0.5 mm, 1.5 mm, and 2 mm, respectively. The Zebra measured values of the range of the single spots also agreed within 1 mm with their established values from other measurements. The Zebra measured DDC of verification plan of patient treatment fields showed goodagreement with those from the TPS. CONCLUSIONS: Our investigation shows that Zebra can be useful for fast and reasonably accurate measurements of the DDC of pristine and spread-out Bragg peaks of both spot scanning and passive scattering proton beams.

Does kV-MV dual-energy computed tomography have an advantage in determining proton stopping power ratios in patients?

Conventional kilovoltage (kV) x-ray-based dual-energy CT (DECT) imaging using two different x-ray energy spectra is sensitive to image noise and beam hardening effects. The purpose of this study was to evaluate the theoretical advantage of the DECT method for determining proton stopping power ratios (SPRs) using a combination of kV and megavoltage (MV) x-ray energies. We investigated three representative x-ray energy pairs: 100 and 140 kVp comprised the kV-kV pair, 100 kVp and 1 MV comprised the kV-MV pair, and two 1 MV x-ray beams-one with and one without external filtration-comprised the MV-MV pair. The SPRs of 34 human tissues were determined using the DECT method with these three x-ray energy pairs. Small perturbations were introduced into the CT numbers and x-ray spectra used for the DECT calculation to simulate the effects of random noise and beam hardening. An error propagation analysis was performed on the DECT calculation algorithm to investigate the propagation of CT number uncertainty to final SPR estimation and to suggest the best x-ray energy combination. We found that the DECT method using each of the three beam pairs achieved similar accuracy in determining the SPRs of human tissues in ideal conditions. However, when CT number uncertainties and artifacts such as imaging noise and beam hardening effects were considered, the kV-MV DECT improved the accuracy of SPR estimation substantially over the kV-kV or MV-MV DECT methods. Furthermore, our error propagation analysis showed that the combination of 100 kVp and 1 MV beams was close to the optimal selection when using the DECT method to determine SPRs. Overall, the kV-MV combination makes the DECT method more robust in resolving the effective atomic numbers for biological tissues than the traditional kV-kV DECT method.

Intensity modulated proton therapy treatment planning using single-field optimization: the impact of monitor unit constraints on plan quality.

PURPOSE: To investigate the effect of monitor unit (MU) constraints on the dose distribution created by intensity modulated proton therapy (IMPT) treatment planning using single-field optimization (SFO). METHODS: Ninety-four energies between 72.5 and 221.8 MeV are available for scanning beam IMPT delivery at our institution. The minimum and maximum MUs for delivering each pencil beam (spot) are 0.005 and 0.04, respectively. These MU constraints are not considered during optimization by the treatment planning system; spots are converted to deliverable MUs during postprocessing. Treatment plans for delivering uniform doses to rectangular volumes with and without MU constraints were generated for different target doses, spot spacings, spread-out Bragg peak (SOBP) widths, and ranges in a homogeneous phantom. Four prostate cancer patients were planned with and without MU constraints using different spot spacings. Rounding errors were analyzed using an in-house software tool. RESULTS: From the phantom study, the authors have found that both the number of spots that have rounding errors and the magnitude of the distortion of the dose distribution from the ideally optimized distribution increases as the field dose, spot spacing, and range decrease and as the SOBP width increases. From our study of patient plans, it is clear that as the spot spacing decreases the rounding error increases, and the dose coverage of the target volume becomes unacceptable for very small spot spacings. CONCLUSIONS: Constraints on deliverable MU for each spot could create a significant distortion from the ideally optimized dose distributions for IMPT fields using SFO. To eliminate this problem, the treatment planning system should incorporate the MU constraints in the optimization process and the delivery system should reliably delivery smaller minimum MUs.

Theoretical variance analysis of single- and dual-energy computed tomography methods for calculating proton stopping power ratios of biological tissues.

We discovered an empirical relationship between the logarithm of mean excitation energy (ln Im) and the effective atomic number (EAN) of human tissues, which allows for computing patient-specific proton stopping power ratios (SPRs) using dual-energy CT (DECT) imaging. The accuracy of the DECT method was evaluated for 'standard' human tissues as well as their variance. The DECT method was compared to the existing standard clinical practice-a procedure introduced by Schneider et al at the Paul Scherrer Institute (the stoichiometric calibration method). In this simulation study, SPRs were derived from calculated CT numbers of known material compositions, rather than from measurement. For standard human tissues, both methods achieved good accuracy with the root-mean-square (RMS) error well below 1%. For human tissues with small perturbations from standard human tissue compositions, the DECT method was shown to be less sensitive than the stoichiometric calibration method. The RMS error remained below 1% for most cases using the DECT method, which implies that the DECT method might be more suitable for measuring patient-specific tissue compositions to improve the accuracy of treatment planning for charged particle therapy. In this study, the effects of CT imaging artifacts due to the beam hardening effect, scatter, noise, patient movement, etc were not analyzed. The true potential of the DECT method achieved in theoretical conditions may not be fully achievable in clinical settings. Further research and development may be needed to take advantage of the DECT method to characterize individual human tissues.

Assessment of the accuracy of an MCNPX-based Monte Carlo simulation model for predicting three-dimensional absorbed dose distributions.

In recent years, the Monte Carlo method has been used in a large number of research studies in radiation therapy. For applications such as treatment planning, it is essential to validate the dosimetric accuracy of the Monte Carlo simulations in heterogeneous media. The AAPM Report no 105 addresses issues concerning clinical implementation of Monte Carlo based treatment planning for photon and electron beams, however for proton-therapy planning, such guidance is not yet available. Here we present the results of our validation of the Monte Carlo model of the double scattering system used at our Proton Therapy Center in Houston. In this study, we compared Monte Carlo simulated depth doses and lateral profiles to measured data for a magnitude of beam parameters. We varied simulated proton energies and widths of the spread-out Bragg peaks, and compared them to measurements obtained during the commissioning phase of the Proton Therapy Center in Houston. Of 191 simulated data sets, 189 agreed with measured data sets to within 3% of the maximum dose difference and within 3 mm of the maximum range or penumbra size difference. The two simulated data sets that did not agree with the measured data sets were in the distal falloff of the measured dose distribution, where large dose gradients potentially produce large differences on the basis of minute changes in the beam steering. Hence, the Monte Carlo models of medium- and large-size double scattering proton-therapy nozzles were valid for proton beams in the 100 MeV-250 MeV interval.

Measurements of in-air output ratios for a linear accelerator with and without the flattening filter.

The in-air output ratio (Sc) for photon beams from linear accelerators describes the change of in-air output as a function of the collimator settings. The physical origin of the Sc is mainly due to the change in scattered radiation that can reach the point of measurement as the geometry of the head changes. The flattening filter (FF) and primary collimator are the major sources of scattered radiation. The change in amount of backscattered radiation from the collimator into the beam-monitoring chamber also contributes to the variation of output. In this work, we measured the Sc and backscatter factors (Sb) into the beam-monitoring chamber for a linear accelerator with and without the FF. We measured the Sc with a Farmer-type chamber in a miniphantom at the depth of 10 g/cm2 for 6- and 18-MV x-ray beams from a Varian Clinac 2100EX linear accelerator. The Sb were measured with a universal pulse counter and a diode array with build-in counting hardware and software. The head scatter component (Sh) was then derived from the relationship Sc= Sh x Sb, where Sb was the linear fit of measured results. Significant differences were observed for Sc with and without the FF. Within the range of experimental uncertainty, the Sb was similar with and without the FF. The variations in Sh differed significantly over the range of field sizes of 3 X 3 to 40 X 40 cm2 with and without the FF; for the 6-MV beam, it was 8% vs 3%, and for the 18-MV beam, 7% vs 1%. By analyzing the contributions of backscatter factor and total in-air output ratios with and without the FF, we directly gained insight into the contributions of different components to the total variations in Sc of a linear accelerator. Sc, Sb, and Sh are basic and useful dosimetric quantities for delivery of intensity-modulated radiation therapy using a linear accelerator operating in a mode without the FF.

Derivation of the distribution of extrafocal radiation for head scatter factor calculation.

Head scatter factors for high energy photon beams from linear accelerators can be modeled using a two-source model consisting of focal and extrafocal radiation. The focal radiation can be approximated as a point source, and the distribution of the extrafocal radiation is a two-dimensional (2D) radial symmetric function. Various methods, including analytical, Monte Carlo, and empirical trial functions, have been used to determine the radial symmetric function of extrafocal radiation distribution. This article describes a method for directly determining the extrafocal radiation distribution without assuming any empirical trial function. The extrafocal radiation distribution is determined with measured head scatter factors for rectangular fields defined by the lower jaw (X) fixed at 40 cm and the upper jaw (Y) varying from 3 to 40 cm. The derivatives of the measured head scatter factors, with respect to the Y jaw position projected in the plane of extrafocal radiation, are proportional to the one-dimensional (1D) projection (also called the line spread function) of the extrafocal radiation distribution. Two methods are used to solve the radial function of extrafocal radiation from the 1D projection. The first method uses a 2D filtered backprojection algorithm, originally developed for parallel beam computed tomography reconstruction, to directly derive the radial dependence of the extrafocal radiation distribution. The method has been applied to 6 and 18 MV photon beams from a Siemens linear accelerator and has been tested by comparing measured and calculated head scatter factors for square and rectangular fields. The second method uses a Fourier transform followed by a Fourier-Bessel transform to solve the problem. The distributions of extrafocal radiation derived from these two methods are virtually identical.

Characteristics of sensitometric curves of radiographic films.

A new type of radiographic film, EDR (extended dose range) film, has been recently become available for film dosimetry. It is particularly attractive for composite isodose verification of intensity modulated radiation therapy because of its low sensitivity relative to the more common Kodak XV film. For XV film, the relationship between optical density and dose, commonly known as the sensitometric curve, depends linearly on the dose at low densities. Unlike XV film, the sensitometric curve of EDR film irradiated by megavoltage x rays is not linearly dependent on the dose at low densities. In this work, to understand the mechanisms governing the shape of the sensitometric curves, EDR film was studied with kilovoltage x rays, 60Co gamma rays, megavoltage x rays, and electron beams. As a comparison, XV film was also studied with the same beams mentioned above. The model originally developed by Silberstein [J. Opt. Soc. Am. 35, 93-107, 1945)] is used to fit experimental data. It is found that the single hit model can be used to predict the sensitometric curve for XV films irradiated by all beams used in this work and for EDR films exposed to kilovoltage x rays. For EDR film irradiated by 60Co gamma rays, megavoltage x rays, and electron beams, the double hit model is used to fit the sensitometric curves. For doses less than 100 cGy, a systematic difference between measured densities and that predicted by the double hit model is observed. Possible causes of the observed differences are discussed. The results of this work provide a theoretical explanation of the sensitometric behavior of EDR film.

Expression of MUPP1 protein in mouse brain.

Localizing cell surface receptors to specific subcellular sites can be crucial for proper functioning. PDZ proteins apparently play central roles in such protein localizations. 5-HT(2C) receptors have previously been shown to interact with MUPP1, a multi PDZ domain protein, in heterologous systems and in rat choroid plexus. We now report the generation and characterization of two independent MUPP1 antisera, which recognise distinct areas of the mouse brain in agreement with previous in-situ hybridization studies. Our results indicate that MUPP1 immunoreactivity co-localizes with 5-HT(2A) or 5-HT(2C) receptor expression in all regions of the mouse brain, including the choroid plexus where 5-HT(2C) receptors are highly enriched.

Evaluation of Kodak EDR2 film for dose verification of intensity modulated radiation therapy delivered by a static multileaf collimator.

A new type of radiographic film, Kodak EDR2 film, was evaluated for dose verification of intensity modulated radiation therapy (IMRT) delivered by a static multileaf collimator (SMLC). A sensitometric curve of EDR2 film irradiated by a 6 MV x-ray beam was compared with that of Kodak X-OMAT V (XV) film. The effects of field size, depth and dose rate on the sensitometric curve were also studied. It is found that EDR2 film is much less sensitive than XV film. In high-energy x-ray beams, the double hit process is the dominant mechanism that renders the grains on EDR2 films developable. As a result, in the dose range that is commonly used for film dosimetry for IMRT and conventional external beam therapy, the sensitometric curves of EDR2 films cannot be approximated as a linear function, OD = c * D. Within experimental uncertainty, the film sensitivity does not depend on the dose rate (50 vs 300 MU/min) or dose per pulse (from 1.0 x 10(-4) to 4.21 x 10(-4) Gy/pulse). Field sizes and depths (up to field size of 10 x 10 cm2 and depth = 10 cm) have little effect on the sensitometric curves. Percent depth doses (PDDs) for both 6 and 23 MV x rays were measured with both EDR2 and XV films and compared with ion chamber data. Film data are within 2.5% of the ion chamber results. Dose profiles measured with EDR2 film are consistent with those measured with an ion chamber. Examples of measured IMRT isodose distributions versus calculated isodoses are presented. We have used EDR2 films for verification of all IMRT patients treated by SMLC in our clinic. In most cases, with EDR2 film, actual clinical daily fraction doses can be used for verification of composite isodose distributions of SMLC-based IMRT.