Feasibility of the partial-single arc technique in RapidArc planning for prostate cancer treatment

PubMed Central

Rana, Suresh; Cheng, ChihYao

2013-01-01

The volumetric modulated arc therapy (VMAT) technique, in the form of RapidArc, is widely used to treat prostate cancer. The full-single arc (f-SA) technique in RapidArc planning for prostate cancer treatment provides efficient treatment, but it also delivers a higher radiation dose to the rectum. This study aimed to compare the dosimetric results from the new partial-single arc (p-SA) technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment. In this study, 10 patients with low-risk prostate cancer were selected. For each patient, two sets of RapidArc plans (f-SA and p-SA) were created in the Eclipse treatment planning system. The f-SA plan was created using one full arc, and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors. Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters. The f-SA and p-SA plans showed an average difference of ±1% for the doses to the planning target volume (PTV), and there were no clear differences in dose homogeneity or plan conformity. In comparison to the f-SA technique, the p-SA technique reduced the doses to the rectum by approximately 6.1% to 21.2%, to the bladder by approximately 10.3% to 29.5%, and to the penile bulb by approximately 2.2%. In contrast, the dose to the femoral heads, the integral dose, and the number of monitor units were higher in the p-SA plans by approximately 34.4%, 7.7%, and 9.2%, respectively. In conclusion, it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment. For the same PTV coverage and identical plan optimization parameters, the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique. PMID:23845140

Cost Analysis of Complex Radiation Therapy for Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perrier, Lionel; Morelle, Magali; Department of Clinical Research and Innovation, Leon Berard Cancer Centre, Lyon

2016-06-01

Purpose: This cost analysis aimed to prospectively assess differences in costs between TomoTherapy and volumetric modulated arc therapy (VMAT) in patients with head and neck cancer. Methods and Materials: Economic data were gathered from a multicenter study. However, randomization was not possible due to the availability of equipment. Costs were calculated using the microcosting technique from the hospital's perspective (in 2013 euros), and the time horizon was radiation therapy. Only resources that entered the hospital production process and which were likely to vary between the strategies being compared were considered. Acute adverse events observed within the time horizon were alsomore » assessed. Results: The cost analysis was based on a total of 173 patient treatments given between 2010 and 2012 in 14 French cancer centers: 73 patients were treated with TomoTherapy, 92 with VMAT RapidArc, and 8 with VMAT SmartArc. Estimated costs of SmartArc were removed from the comparison due to the small sample size. The mean ± SD cost per patient of the treatment planning phase was €314 (±€214) for TomoTherapy and €511 (±€590) for RapidArc. Mean costs ± SD per patient of irradiation reached €3144 (±€565) for TomoTherapy and €1350 (±€299) for RapidArc. The most sensitive parameter of irradiation was the annual operating time of accelerators. Ninety-five percent confidence intervals for the mean costs of irradiation were €3016 to €3272 for TomoTherapy and €1281 to €1408 for RapidArc. The number of acute adverse events during radiation therapy was not significantly different between strategies. Conclusions: TomoTherapy appeared to be more expensive than RapidArc mainly due to the higher price of the accelerator, the higher costs of maintenance, and the longer duration of treatment sessions. Because strategies were not significantly different in clinical effect, RapidArc appeared to be the strategy to be recommended at this stage of knowledge.« less

Cost Analysis of Complex Radiation Therapy for Patients With Head and Neck Cancer.

PubMed

Perrier, Lionel; Morelle, Magali; Pommier, Pascal; Boisselier, Pierre; Coche-Dequeant, Bernard; Gallocher, Olivier; Alfonsi, Marc; Bardet, Etienne; Rives, Michel; Calugaru, Valentin; Chajon, Enrique; Noel, Georges; Mecellem, Hinda; Pérol, David; Dussart, Sophie; Giraud, Philippe

2016-06-01

This cost analysis aimed to prospectively assess differences in costs between TomoTherapy and volumetric modulated arc therapy (VMAT) in patients with head and neck cancer. Economic data were gathered from a multicenter study. However, randomization was not possible due to the availability of equipment. Costs were calculated using the microcosting technique from the hospital's perspective (in 2013 euros), and the time horizon was radiation therapy. Only resources that entered the hospital production process and which were likely to vary between the strategies being compared were considered. Acute adverse events observed within the time horizon were also assessed. The cost analysis was based on a total of 173 patient treatments given between 2010 and 2012 in 14 French cancer centers: 73 patients were treated with TomoTherapy, 92 with VMAT RapidArc, and 8 with VMAT SmartArc. Estimated costs of SmartArc were removed from the comparison due to the small sample size. The mean ± SD cost per patient of the treatment planning phase was €314 (±€214) for TomoTherapy and €511 (±€590) for RapidArc. Mean costs ± SD per patient of irradiation reached €3144 (±€565) for TomoTherapy and €1350 (±€299) for RapidArc. The most sensitive parameter of irradiation was the annual operating time of accelerators. Ninety-five percent confidence intervals for the mean costs of irradiation were €3016 to €3272 for TomoTherapy and €1281 to €1408 for RapidArc. The number of acute adverse events during radiation therapy was not significantly different between strategies. TomoTherapy appeared to be more expensive than RapidArc mainly due to the higher price of the accelerator, the higher costs of maintenance, and the longer duration of treatment sessions. Because strategies were not significantly different in clinical effect, RapidArc appeared to be the strategy to be recommended at this stage of knowledge. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of contrast agent administration on consequences of dosimetry and biology in radiotherapy planning

NASA Astrophysics Data System (ADS)

Lo, Ching-Jung; Yang, Pei-Ying; Chao, Tsi-Chian; Tu, Shu-Ju

2015-06-01

In the treatment planning of radiation therapy, patients may be administrated with contrast media in CT scanning to assist physicians for accurate delineation of the target or organs. However, contrast media are not used in patients during the treatment delivery. In particular, contrast media contain materials with high atomic numbers and dosimetric variations may occur between scenarios where contrast media are present in treatment planning and absent in treatment delivery. In this study we evaluate the effect of contrast media on the dosimetry and biological consequence. An analytical phantom based on AAPM TG 119 and five sets of CT images from clinical patients are included. Different techniques of treatment planning are considered, including 1-field AP, 2-field AP+PA, 4-field box, 7-field IMRT, and RapidArc. RapidArc is a recent technique of volumetric modulated arc therapy and is used in our study of contrast media in clinical scenarios. The effect of RapidArc on dosimetry and biological consequence for administration of contrast media in radiotherapy is not discussed previously in literature. It is shown that dose difference is reduced as the number of external beams is increased, suggesting RapidArc may be favored to be used in the treatment planning enhanced by contrast media. Linear trend lines are fitted for assessment of percent dose differences in the planning target volume versus concentrations of contrast media between plans where contrast media are present and absent, respectively.

Volumetric Modulated Arc-Based Hypofractionated Stereotactic Radiotherapy for the Treatment of Selected Intracranial Arteriovenous Malformations: Dosimetric Report and Early Clinical Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subramanian, Sai; Srinivas, Chilukuri; Ramalingam, K.

2012-03-01

Purpose: To evaluate, with a dosimetric and clinical feasibility study, RapidArc (a volumetric modulated arc technique) for hypofractionated stereotactic radiotherapy treatment of large arteriovenous malformations (AVMs). Methods and Materials: Nine patients were subject to multimodality imaging (magnetic resonance, computed tomography, and digital subtraction angiography) to determine nidus and target volumes, as well as involved organs at risk (optical structures, inner ear, brain stem). Plans for multiple intensity-modulated arcs with a single isocenter were optimized for a fractionation of 25 Gy in 5 fractions. All plans were optimized for 6-MV photon beams. Dose-volume histograms were analyzed to assess plan quality. Deliverymore » parameters were reported to appraise technical features of RapidArc, and pretreatment quality assurance measurements were carried out to report on quality of delivery. Results: Average size of AVM nidus was 26.2 cm{sup 3}, and RapidArc plans provided complete target coverage with minimal overdosage (V{sub 100%} = 100% and V{sub 110%} < 1%) and excellent homogeneity (<6%). Organs at risk were highly spared. The D{sub 1%} to chiasm, eyes, lenses, optic nerves, and brainstem (mean {+-} SD) was 6.4 {+-} 8.3, 1.9 {+-} 3.8, 2.3 {+-} 2.2, 0.7 {+-} 0.9, 4.4 {+-} 7.2, 12.2 {+-} 9.6 Gy, respectively. Conformity index (CI{sub 95%}) was 2.2 {+-} 0.1. The number of monitor units per gray was 277 {+-} 45, total beam-on time was 2.5 {+-} 0.3 min. Planning vs. delivery {gamma} pass rate was 98.3% {+-} 0.9%. None of the patients developed acute toxicity. With a median follow-up of 9 months, 3 patients presented with deterioration of symptoms and were found to have postradiation changes but responded symptomatically to steroids. These patients continue to do well on follow-up. One patient developed headache and seizures, which was attributed to intracranial bleed, confirmed on imaging. Conclusion: Hypofractionated stereotactic radiotherapy can be successfully delivered using the RapidArc form of volumetric arc technology for intracranial AVMs. The quality of delivery and calculated parameters are in agreement with each other and are in line with published reports for other sites.« less

Dosimetric Impact of Using the Acuros XB Algorithm for Intensity Modulated Radiation Therapy and RapidArc Planning in Nasopharyngeal Carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kan, Monica W.K., E-mail: kanwkm@ha.org.hk; Department of Physics and Materials Science, City University of Hong Kong, Hong Kong; Leung, Lucullus H.T.

2013-01-01

Purpose: To assess the dosimetric implications for the intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy with RapidArc (RA) of nasopharyngeal carcinomas (NPC) due to the use of the Acuros XB (AXB) algorithm versus the anisotropic analytical algorithm (AAA). Methods and Materials: Nine-field sliding window IMRT and triple-arc RA plans produced for 12 patients with NPC using AAA were recalculated using AXB. The dose distributions to multiple planning target volumes (PTVs) with different prescribed doses and critical organs were compared. The PTVs were separated into components in bone, air, and tissue. The change of doses by AXB duemore » to air and bone, and the variation of the amount of dose changes with number of fields was also studied using simple geometric phantoms. Results: Using AXB instead of AAA, the averaged mean dose to PTV{sub 70} (70 Gy was prescribed to PTV{sub 70}) was found to be 0.9% and 1.2% lower for IMRT and RA, respectively. It was approximately 1% lower in tissue, 2% lower in bone, and 1% higher in air. The averaged minimum dose to PTV{sub 70} in bone was approximately 4% lower for both IMRT and RA, whereas it was approximately 1.5% lower for PTV{sub 70} in tissue. The decrease in target doses estimated by AXB was mostly contributed from the presence of bone, less from tissue, and none from air. A similar trend was observed for PTV{sub 60} (60 Gy was prescribed to PTV{sub 60}). The doses to most serial organs were found to be 1% to 3% lower and to other organs 4% to 10% lower for both techniques. Conclusions: The use of the AXB algorithm is highly recommended for IMRT and RapidArc planning for NPC cases.« less

On the role of the optimization algorithm of RapidArc(®) volumetric modulated arc therapy on plan quality and efficiency.

PubMed

Vanetti, Eugenio; Nicolini, Giorgia; Nord, Janne; Peltola, Jarkko; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

2011-11-01

The RapidArc volumetric modulated arc therapy (VMAT) planning process is based on a core engine, the so-called progressive resolution optimizer (PRO). This is the optimization algorithm used to determine the combination of field shapes, segment weights (with dose rate and gantry speed variations), which best approximate the desired dose distribution in the inverse planning problem. A study was performed to assess the behavior of two versions of PRO. These two versions mostly differ in the way continuous variables describing the modulated arc are sampled into discrete control points, in the planning efficiency and in the presence of some new features. The analysis aimed to assess (i) plan quality, (ii) technical delivery aspects, (iii) agreement between delivery and calculations, and (iv) planning efficiency of the two versions. RapidArc plans were generated for four groups of patients (five patients each): anal canal, advanced lung, head and neck, and multiple brain metastases and were designed to test different levels of planning complexity and anatomical features. Plans from optimization with PRO2 (first generation of RapidArc optimizer) were compared against PRO3 (second generation of the algorithm). Additional plans were optimized with PRO3 using new features: the jaw tracking, the intermediate dose and the air cavity correction options. Results showed that (i) plan quality was generally improved with PRO3 and, although not for all parameters, some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3 optimization leads to simpler patterns of the dynamic parameters particularly for dose rate. (iii) No differences were observed between the two algorithms in terms of pretreatment quality assurance measurements and (iv) PRO3 optimization was generally faster, with a time reduction of a factor approximately 3.5 with respect to PRO2. These results indicate that PRO3 is either clinically beneficial or neutral in terms of dosimetric quality while it showed significant advantages in speed and technical aspects.

Dependence of Achievable Plan Quality on Treatment Technique and Planning Goal Refinement: A Head-and-Neck Intensity Modulated Radiation Therapy Application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, X. Sharon, E-mail: xqi@mednet.ucla.edu; Ruan, Dan; Lee, Steve P.

2015-03-15

Purpose: To develop a practical workflow for retrospectively analyzing target and normal tissue dose–volume endpoints for various intensity modulated radiation therapy (IMRT) delivery techniques; to develop technique-specific planning goals to improve plan consistency and quality when feasible. Methods and Materials: A total of 165 consecutive head-and-neck patients from our patient registry were selected and retrospectively analyzed. All IMRT plans were generated using the same dose–volume guidelines for TomoTherapy (Tomo, Accuray), TrueBeam (TB, Varian) using fixed-field IMRT (TB-IMRT) or RAPIDARC (TB-RAPIDARC), or Siemens Oncor (Siemens-IMRT, Siemens). A MATLAB-based dose–volume extraction and analysis tool was developed to export dosimetric endpoints for eachmore » patient. With a fair stratification of patient cohort, the variation of achieved dosimetric endpoints was analyzed among different treatment techniques. Upon identification of statistically significant variations, technique-specific planning goals were derived from dynamically accumulated institutional data. Results: Retrospective analysis showed that although all techniques yielded comparable target coverage, the doses to the critical structures differed. The maximum cord doses were 34.1 ± 2.6, 42.7 ± 2.1, 43.3 ± 2.0, and 45.1 ± 1.6 Gy for Tomo, TB-IMRT, TB-RAPIDARC, and Siemens-IMRT plans, respectively. Analyses of variance showed significant differences for the maximum cord doses but no significant differences for other selected structures among the investigated IMRT delivery techniques. Subsequently, a refined technique-specific dose–volume guideline for maximum cord dose was derived at a confidence level of 95%. The dosimetric plans that failed the refined technique-specific planning goals were reoptimized according to the refined constraints. We observed better cord sparing with minimal variations for the target coverage and other organ at risk sparing for the Tomo cases, and higher parotid doses for C-arm linear accelerator–based IMRT and RAPIDARC plans. Conclusion: Patient registry–based processes allowed easy and systematic dosimetric assessment of treatment plan quality and consistency. Our analysis revealed the dependence of certain dosimetric endpoints on the treatment techniques. Technique-specific refinement of planning goals may lead to improvement in plan consistency and plan quality.« less

SU-E-T-393: Evaluation of Large Field IMRT Versus RapidArc Planning for Carcinoma Cervix with Para-Aotic Node Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raman, S Kothanda; Girigesh, Y; MISHRA, M

Purpose: The objective of this work is to evaluate and compare Large field IMRT and RapidArc planning for Carcinoma Cervix and Para-aotic node irradiation. Methods: In this study, ten patients of Cervix with para-aotic node have been selected with PTV length 35+2cm. All plans were generated in Eclipse TPS V10.0 with Dynamic IMRT and RapidArc technique using 6MV photon energy. In IMRT planning, 7 fields were chosen to get optimal plan and in RapidArc, double Full arc clockwise and counter clockwise were used for planning. All the plans were generated with single isocenter and calculated using AAA dose algorithm. Formore » all the cases the prescribed dose to PTV was same and the plan acceptance criteria is; 95% of the PTV volume should receive 100% prescribed dose. The tolerance doses for the OAR’s is also taken in to account. The evaluation criteria used for analysis are; 1) Homogeneity Index, 2) Conformity Index, 3) Mean Dose to OAR’s, 4)Total monitor units delivered. Results: DVH analysis were performed for both IMRT and RapidArc planning. In both the plans, 95% of PTV volume receives prescribed dose and maximum dose are less than 107%. The conformity index are same in both the techniques. The mean Homogeneity index are 1.036 and 1.053 for IMRT and RapidArc plan. The mean (mean + SD) dose of bladder and rectum in IMRT is 44.2+1.55, 42.05+2.52 and RapidArc is 46.66+1.6, 44.2+2.75 respectively. There is no significant difference found in Right Femoral head, Left Femoral head and Kidney doses. It is found that total MU’s are more in IMRT compared with RapidArc planning. Conclusion: In the case of cervix with Para-arotic node single isocenter irradiation, IMRT planning in large-field is better compared to RapidArc planning in terms of Homogeneity Index and mean dose of Bladder and Rectum.« less

A comparative study of standard intensity-modulated radiotherapy and RapidArc planning techniques for ipsilateral and bilateral head and neck irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pursley, Jennifer, E-mail: jpursley@mgh.harvard.edu; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Damato, Antonio L.

The purpose of this study was to investigate class solutions using RapidArc volumetric-modulated arc therapy (VMAT) planning for ipsilateral and bilateral head and neck (H&N) irradiation, and to compare dosimetric results with intensity-modulated radiotherapy (IMRT) plans. A total of 14 patients who received ipsilateral and 10 patients who received bilateral head and neck irradiation were retrospectively replanned with several volumetric-modulated arc therapy techniques. For ipsilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the contralateral parotid, two 260° or 270° arcs, and two 210° arcs. For bilateral neck irradiation, themore » volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the shoulders, and 3 arcs. All patients had a sliding-window-delivery intensity-modulated radiotherapy plan that was used as the benchmark for dosimetric comparison. For ipsilateral neck irradiation, a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid was dosimetrically comparable to intensity-modulated radiotherapy, with improved conformity (conformity index = 1.22 vs 1.36, p < 0.04) and lower contralateral parotid mean dose (5.6 vs 6.8 Gy, p < 0.03). For bilateral neck irradiation, 3-arc volumetric-modulated arc therapy techniques were dosimetrically comparable to intensity-modulated radiotherapy while also avoiding irradiation through the shoulders. All volumetric-modulated arc therapy techniques required fewer monitor units than sliding-window intensity-modulated radiotherapy to deliver treatment, with an average reduction of 35% for ipsilateral plans and 67% for bilateral plans. Thus, for ipsilateral head and neck irradiation a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid is recommended. For bilateral neck irradiation, 2- or 3-arc techniques are dosimetrically comparable to intensity-modulated radiotherapy, but more work is needed to determine the optimal approaches by disease site.« less

A comparative study of standard intensity-modulated radiotherapy and RapidArc planning techniques for ipsilateral and bilateral head and neck irradiation.

PubMed

Pursley, Jennifer; Damato, Antonio L; Czerminska, Maria A; Margalit, Danielle N; Sher, David J; Tishler, Roy B

2017-01-01

The purpose of this study was to investigate class solutions using RapidArc volumetric-modulated arc therapy (VMAT) planning for ipsilateral and bilateral head and neck (H&N) irradiation, and to compare dosimetric results with intensity-modulated radiotherapy (IMRT) plans. A total of 14 patients who received ipsilateral and 10 patients who received bilateral head and neck irradiation were retrospectively replanned with several volumetric-modulated arc therapy techniques. For ipsilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the contralateral parotid, two 260° or 270° arcs, and two 210° arcs. For bilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the shoulders, and 3 arcs. All patients had a sliding-window-delivery intensity-modulated radiotherapy plan that was used as the benchmark for dosimetric comparison. For ipsilateral neck irradiation, a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid was dosimetrically comparable to intensity-modulated radiotherapy, with improved conformity (conformity index = 1.22 vs 1.36, p < 0.04) and lower contralateral parotid mean dose (5.6 vs 6.8Gy, p < 0.03). For bilateral neck irradiation, 3-arc volumetric-modulated arc therapy techniques were dosimetrically comparable to intensity-modulated radiotherapy while also avoiding irradiation through the shoulders. All volumetric-modulated arc therapy techniques required fewer monitor units than sliding-window intensity-modulated radiotherapy to deliver treatment, with an average reduction of 35% for ipsilateral plans and 67% for bilateral plans. Thus, for ipsilateral head and neck irradiation a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid is recommended. For bilateral neck irradiation, 2- or 3-arc techniques are dosimetrically comparable to intensity-modulated radiotherapy, but more work is needed to determine the optimal approaches by disease site. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Comparative dosimetric and radiobiological assessment among a nonstandard RapidArc, standard RapidArc, classical intensity-modulated radiotherapy, and 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecologic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pedicini, Piernicola, E-mail: ppiern@libero.it; Caivano, Rocchina; Fiorentino, Alba

2012-01-01

To evaluate a nonstandard RapidArc (RA) modality as alternative to high-dose-rate brachytherapy (HDR-BRT) or IMRT treatments of the vaginal vault in patients with gynecological cancer (GC). Nonstandard (with vaginal applicator) and standard (without vaginal applicator) RapidArc plans for 27 women with GC were developed to compare with HDR-BRT and IMRT. Dosimetric and radiobiological comparison were performed by means of dose-volume histogram and equivalent uniform dose (EUD) for planning target volume (PTV) and organs at risk (OARs). In addition, the integral dose and the overall treatment times were evaluated. RA, as well as IMRT, results in a high uniform dose onmore » PTV compared with HDR-BRT. However, the average of EUD for HDR-BRT was significantly higher than those with RA and IMRT. With respect to the OARs, standard RA was equivalent of IMRT but inferior to HDR-BRT. Furthermore, nonstandard RA was comparable with IMRT for bladder and sigmoid and better than HDR-BRT for the rectum because of a significant reduction of d{sub 2cc}, d{sub 1cc}, and d{sub max} (p < 0.01). Integral doses were always higher than HDR-BRT, although the values were very low. Delivery times were about the same and more than double for HDR-BRT compared with IMRT and RA, respectively. In conclusion, the boost of dose on vaginal vault in patients affected by GC delivered by a nonstandard RA technique was a reasonable alternative to the conventional HDR-BRT because of a reduction of delivery time and rectal dose at substantial comparable doses for the bladder and sigmoid. However HDR-BRT provides better performance in terms of PTV coverage as evidenced by a greater EUD.« less

TU-E-BRB-08: Dual Gated Volumetric Modulated Arc Therapy.

PubMed

Wu, J; Fahimian, B; Wu, H; Xing, L

2012-06-01

Gated Volumetric Modulated Arc Therapy (VMAT) is an emerging treatment modality for Stereotactic Body Radiotherapy (SBRT). However, gating significantly prolongs treatment time. In order to enhance treatment efficiency, a novel dual gated VMAT, in which dynamic arc deliveries are executed sequentially in alternating exhale and inhale phases, is proposed and evaluated experimentally. The essence of dual gated VMAT is to take advantage of the natural pauses that occur at inspiration and exhalation by alternatively delivering the dose at the two phases, instead of the exhale window only. The arc deliveries at the two phases are realized by rotating gantry forward at the exhale window and backward at the inhale in an alternative fashion. Custom XML scripts were developed in Varian's TrueBeam STx Developer Mode to enable dual gated VMAT delivery. RapidArc plans for a lung case were generated for both inhale and exhale phases. The two plans were then combined into a dual gated arc by interleaving the arc treatment nodes of the two RapidArc plans. The dual gated plan was delivered in the development mode of TrueBeam LINAC onto a motion phantom and the delivery was measured by using pinpoint chamber/film/diode array (delta 4). The measured dose distribution was compared with that computed using Eclipse AAA algorithm. The treatment delivery time was recorded and compared with the corresponding single gated plans. Relative to the corresponding single gated delivery, it was found that treatment time efficiency was improved by 95.5% for the case studied here. Pinpoint chamber absolute dose measurement agreed the calculation to within 0.7%. Diode chamber array measurements revealed that 97.5% of measurement points of dual gated RapidArc delivery passed the 3% and 3mm gamma-test criterion. A dual gated VMAT treatment has been developed and implemented successfully with nearly doubled treatment delivery efficiency. © 2012 American Association of Physicists in Medicine.

Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications.

PubMed

Wolff, Hendrik Andreas; Wagner, Daniela Melanie; Conradi, Lena-Christin; Hennies, Steffen; Ghadimi, Michael; Hess, Clemens Friedrich; Christiansen, Hans

2012-01-01

Ongoing clinical trials aim to improve local control and overall survival rates by intensification of therapy regimen for patients with locally advanced rectal cancer. It is well known that whenever treatment is intensified, risk of therapy-related toxicity rises. An irradiation with protons could possibly present an approach to solve this dilemma by lowering the exposure to the organs-at-risk (OAR) without compromising tumor response. Twenty five consecutive patients were treated from 04/2009 to 5/2010. For all patients, four different treatment plans including protons, RapidArc, IMRT and 3D-conformal-technique were retrospectively calculated and analyzed according to dosimetric aspects. Detailed DVH-analyses revealed that protons clearly reduced the dose to the OAR and entire normal tissue when compared to other techniques. Furthermore, the conformity index was significantly better and target volumes were covered consistent with the ICRU guidelines. Planning results suggest that treatment with protons can improve the therapeutic tolerance for the irradiation of rectal cancer, particularly for patients scheduled for an irradiation with an intensified chemotherapy regimen and identified to be at high risk for acute therapy-related toxicity. However, clinical experiences and long-term observation are needed to assess tumor response and related toxicity rates. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

SU-E-T-125: Application of Jaw-Tracking Function in VMAT for Upper Thoracic Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, W; Chen, J; Zhai, T

2015-06-15

Purpose: To explore the effect of the Jaw-tracking with RapidArc(JT-RapidArc) plans for upper thoracic esophageal cancer. Methods: Treatment planning was designed by using RapidArc and JT-RapidArc techniques for 11 consecutive patients. The dose-volume histogram parameters of PTV and the organs at risk(OAR), conformity index(CI), heterogeneity index(HI), low dose volume of normal tissue(B-P) and monitor units(MUs) were compared between the different techniques. Results: JT-RapidArc plans provided the better coverage of PTV1(64) D98 and HI(P<0.05), lower MLD, D2 of PTV1(64) and PTV2(54), but no statistically difference in CI(P>0.05), which comparison with RapidArc plans. Plans with JT- RapidArc had lower Lung of V5,more » V10, V13, V20, V30, MLD(P<0.05); heart of V20, MLD(P<0.05); and B-P of V5, V10, V15, V20, V30(P<0.05); but no significantly different in Spinal cord and SC-PRV as compared with RapidArc plans. JT-RapidArc plans increaseed the MUs by 1%(P>0.05) as compared with RapidArc plans. Conclusion: All of the plans had met the requirements of clinical dosimetry. JT-RapidArc plans as compared with RapidArc plans, showing better part of target coverage, part of OARS(lung and heart) and heart and B-P sparing, which MUs was slightly increased. This work was sponsored by Shantou University Medical College Clinical Research Enhancement Initiative(NO.201424)« less

Feasibility study of an intensity-modulated radiation model for the study of erectile dysfunction.

PubMed

Koontz, Bridget F; Yan, Hui; Kimura, Masaki; Vujaskovic, Zeljko; Donatucci, Craig; Yin, Fang-Fang

2011-02-01

Preclinical studies of radiotherapy (RT) induced erectile dysfunction (ED) have been limited by radiation toxicity when using large fields. To develop a protocol of rat prostate irradiation using techniques mimicking the current clinical standard of intensity modulated radiotherapy (IMRT). Quality assurance (QA) testing of plan accuracy, animal health 9 weeks after RT, and intracavernosal pressure (ICP) measurement on cavernosal nerve stimulation. Computed tomography-based planning was used to develop a stereotactic radiosurgery (SRS) treatment plan for five young adult male Sprague-Dawley rats. Two treatment planning strategies were utilized to deliver 20 Gy in a single fraction: three-dimensional dynamic conformal arc and intensity-modulated arc (RapidArc). QA testing was performed for each plan type. Treatment was delivered using a NovalisTX (Varian Medical Systems) with high-definition multi-leaf collimators using on-board imaging prior to treatment. Each animal was evaluated for ED 2 months after treatment by nerve stimulation and ICP measurement. The mean prostate volume and target volume (5 mm expansion of prostate) for the five animals was 0.36 and 0.66 cm3, respectively. Both conformal and RapidArc plans provided at least 95% coverage of the target volume, with rapid dose fall-off. QA plans demonstrated strong agreement between doses of calculated and delivered plans, although the conformal arc plan was more homogenous in treatment delivery. Treatment was well tolerated by the animals with no toxicity out to 9 weeks. Compared with control animals, significant reduction in ICP/mean arterial pressure, maximum ICP, and ICP area under the curve were noted. Tightly conformal dynamic arc prostate irradiation is feasible and results in minimal toxicity and measurable changes in erectile function. © 2010 International Society for Sexual Medicine.

A retrospective planning analysis comparing intensity modulated radiation therapy (IMRT) to volumetric modulated arc therapy (VMAT) using two optimization algorithms for the treatment of early-stage prostate cancer

PubMed Central

Elith, Craig A; Dempsey, Shane E; Warren-Forward, Helen M

2013-01-01

Introduction The primary aim of this study is to compare intensity modulated radiation therapy (IMRT) to volumetric modulated arc therapy (VMAT) for the radical treatment of prostate cancer using version 10.0 (v10.0) of Varian Medical Systems, RapidArc radiation oncology system. Particular focus was placed on plan quality and the implications on departmental resources. The secondary objective was to compare the results in v10.0 to the preceding version 8.6 (v8.6). Methods Twenty prostate cancer cases were retrospectively planned using v10.0 of Varian's Eclipse and RapidArc software. Three planning techniques were performed: a 5-field IMRT, VMAT using one arc (VMAT-1A), and VMAT with two arcs (VMAT-2A). Plan quality was assessed by examining homogeneity, conformity, the number of monitor units (MUs) utilized, and dose to the organs at risk (OAR). Resource implications were assessed by examining planning and treatment times. The results obtained using v10.0 were also compared to those previously reported by our group for v8.6. Results In v10.0, each technique was able to produce a dose distribution that achieved the departmental planning guidelines. The IMRT plans were produced faster than VMAT plans and displayed improved homogeneity. The VMAT plans provided better conformity to the target volume, improved dose to the OAR, and required fewer MUs. Treatments using VMAT-1A were significantly faster than both IMRT and VMAT-2A. Comparison between versions 8.6 and 10.0 revealed that in the newer version, VMAT planning was significantly faster and the quality of the VMAT dose distributions produced were of a better quality. Conclusion VMAT (v10.0) using one or two arcs provides an acceptable alternative to IMRT for the treatment of prostate cancer. VMAT-1A has the greatest impact on reducing treatment time. PMID:26229615

Monte Carlo based, patient-specific RapidArc QA using Linac log files.

PubMed

Teke, Tony; Bergman, Alanah M; Kwa, William; Gill, Bradford; Duzenli, Cheryl; Popescu, I Antoniu

2010-01-01

A Monte Carlo (MC) based QA process to validate the dynamic beam delivery accuracy for Varian RapidArc (Varian Medical Systems, Palo Alto, CA) using Linac delivery log files (DynaLog) is presented. Using DynaLog file analysis and MC simulations, the goal of this article is to (a) confirm that adequate sampling is used in the RapidArc optimization algorithm (177 static gantry angles) and (b) to assess the physical machine performance [gantry angle and monitor unit (MU) delivery accuracy]. Ten clinically acceptable RapidArc treatment plans were generated for various tumor sites and delivered to a water-equivalent cylindrical phantom on the treatment unit. Three Monte Carlo simulations were performed to calculate dose to the CT phantom image set: (a) One using a series of static gantry angles defined by 177 control points with treatment planning system (TPS) MLC control files (planning files), (b) one using continuous gantry rotation with TPS generated MLC control files, and (c) one using continuous gantry rotation with actual Linac delivery log files. Monte Carlo simulated dose distributions are compared to both ionization chamber point measurements and with RapidArc TPS calculated doses. The 3D dose distributions were compared using a 3D gamma-factor analysis, employing a 3%/3 mm distance-to-agreement criterion. The dose difference between MC simulations, TPS, and ionization chamber point measurements was less than 2.1%. For all plans, the MC calculated 3D dose distributions agreed well with the TPS calculated doses (gamma-factor values were less than 1 for more than 95% of the points considered). Machine performance QA was supplemented with an extensive DynaLog file analysis. A DynaLog file analysis showed that leaf position errors were less than 1 mm for 94% of the time and there were no leaf errors greater than 2.5 mm. The mean standard deviation in MU and gantry angle were 0.052 MU and 0.355 degrees, respectively, for the ten cases analyzed. The accuracy and flexibility of the Monte Carlo based RapidArc QA system were demonstrated. Good machine performance and accurate dose distribution delivery of RapidArc plans were observed. The sampling used in the TPS optimization algorithm was found to be adequate.

SU-D-BRB-04: Plan Quality Comparison of Intracranial Stereotactic Radiosurgery (SRS) for Gamma Knife and VMAT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Algan, O; Ahmad, S

2015-06-15

Purpose: To compare treatment plan quality of intracranial stereotactic radiosurgery (SRS) for VMAT (RapidArc) and Gamma Knife (GK) systems. Methods: Ten patients with 24 tumors (seven with 1–2 and three with 4–6 lesions), previously treated with GK 4C (prescription doses ranging from 14–23 Gy) were re-planned for RapidArc. Identical contour sets were kept on MRI images for both plans with tissues assigned a CT number of zero. RapidArc plans were performed using 6 MV flattening-filter-free (FFF) beams with dose rate of 1400 MU/minute using two to eight arcs with the following combinations: 2 full coplanar arcs and the rest non-coplanarmore » half arcs. Beam selection was based on target depth. Areas that penetrated more than 10 cm of tissue were avoided by creating smaller arcs or using avoidance sectors in optimization. Plans were optimized with jaw tracking and a high weighting to the normal-brain-tissue and Normal-Tissue-Objective without compromising PTV coverage. Plans were calculated on a 1 mm grid size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4, V8, and V12 Gy, and integral dose. Results: In all cases critical structure dose criteria were met. RapidArc had a higher PCI than GK plans for 23 out of 24 lesions. The average PCI was 0.76±0.21 for RapidArc and 0.46±0.20 for GK plans (p≤0.001), respectively. Integral dose and normal-brain-tissue doses for all criteria were lower for RapidArc in nearly all patients. The average ratio of GK to RapidArc plans was 1.28±0.27 (p=0.018), 1.31±0.25 (p=0.017), 1.81±0.43 (p=0.005), and 1.50±0.61 (p=0.006) for V4, V8, and V12 Gy, and integral dose, respectively. Conclusion: VMAT was capable of producing higher quality treatment plans than GK when using optimal beam geometries and proper optimization techniques.« less

SU-F-T-339: Comparison Between Coplanar and Non-Coplanar RapidArc Approach of Hippocampal-Sparing Whole Brain Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, B; Kim, J

Purpose: To compare the dosimetry of coplanar and non-coplanar RapidArc whole brain plans for hippocampal sparing Methods: We studied the RapidArc plans of patient with brain metastases, with the prescription of 3750 cGy in 15 fractions. The coplanar approach used a full clockwise (CW) arc and a full counterclockwise (CCW) arc, with the couch angle to be 0°. The non-coplanar approach used a full arc with a couch angle of 0°, and a partial arc with a couch angle of 90°. Treatment planning system is Eclipse Ver. 11. Constraints for eyes, lens, brainstem, optical nerves and chiasm are employed inmore » the optimization so that these OARs’ dose are below tolerance. Constraints for hippocampus are employed so that they receive dose as low as possible while maintain good coverage to whole brain. The beam delivery machine is Varian 21 IX. T1-weighted MRI images were used for hippocampus contouring. Results: The target coverage index for coplanar and non-coplanar RapidArc plans are 94.9% and 95.4%, respectively, with homogeneity index of 0.223 vs 0.226, which is defined as (D2% – D98%)/Dmean of target volume. V95 and V100 are 99.0% and 94.8% for coplanar plan, vs 99.1% and 95.4% for non-coplanar plan, while the mean dose of hippocampus are 1244.5 cGy for coplanar plan vs 1212.3 cGy for non-coplanar plan. Dose for eyes, lens, optical nerves, optical chiasm and brainstem are all below tolerance. Conclusion: Coplanar RapidArc plan provides good target coverage while achieves good hippocampal sparing, and there is no benefit to use non-coplanar approach.« less

Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal

2014-08-15

Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dosemore » differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.« less

AAA and AXB algorithms for the treatment of nasopharyngeal carcinoma using IMRT and RapidArc techniques.

PubMed

Kamaleldin, Maha; Elsherbini, Nader A; Elshemey, Wael M

2017-09-27

The aim of this study is to evaluate the impact of anisotropic analytical algorithm (AAA) and 2 reporting systems (AXB-D m and AXB-D w ) of Acuros XB algorithm (AXB) on clinical plans of nasopharyngeal patients using intensity-modulated radiotherapy (IMRT) and RapidArc (RA) techniques. Six plans of different algorithm-technique combinations are performed for 10 patients to calculate dose-volume histogram (DVH) physical parameters for planning target volumes (PTVs) and organs at risk (OARs). The number of monitor units (MUs) and calculation time are also determined. Good coverage is reported for all algorithm-technique combination plans without exceeding the tolerance for OARs. Regardless of the algorithm, RA plans persistently reported higher D 2% values for PTV-70. All IMRT plans reported higher number of MUs (especially with AXB) than did RA plans. AAA-IMRT produced the minimum calculation time of all plans. Major differences between the investigated algorithm-technique combinations are reported only for the number of MUs and calculation time parameters. In terms of these 2 parameters, it is recommended to employ AXB in calculating RA plans and AAA in calculating IMRT plans to achieve minimum calculation times at reduced number of MUs. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dosimetric and radiobiological comparison of Forward Tangent Intensity Modulated Radiation Therapy (FT-IMRT) and Volumetric Modulated Arc Therapy (VMAT) for early stage whole breast cancer

NASA Astrophysics Data System (ADS)

Moshiri Sedeh, Nader

Intensity Modulated Radiation Therapy (IMRT) is a well-known type of external beam radiation therapy. The advancement in technology has had an inevitable influence in radiation oncology as well that has led to a newer and faster dose delivery technique called Volumetric Modulated Arc Therapy (VMAT). Since the presence of the VMAT modality in clinics in the late 2000, there have been many studies in order to compare the results of the VMAT modality with the current popular modality IMRT for various tumor sites in the body such as brain, prostate, head and neck, cervix and anal carcinoma. This is the first study to compare VMAT with IMRT for breast cancer. The results show that the RapidArc technique in Eclipse version 11 does not improve all aspects of the treatment plans for the breast cases automatically and easily, but it needs to be manipulated by extra techniques to create acceptable plans thus further research is needed.

Application of modified dynamic conformal arc (MDCA) technique on liver stereotactic body radiation therapy (SBRT) planning following RTOG 0438 guideline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Chengyu, E-mail: shicy1974@yahoo.com; Chen, Yong; Fang, Deborah

2015-04-01

Liver stereotactic body radiation therapy (SBRT) is a feasible treatment method for the nonoperable, patient with early-stage liver cancer. Treatment planning for the SBRT is very important and has to consider the simulation accuracy, planning time, treatment efficiency effects etc. The modified dynamic conformal arc (MDCA) technique is a 3-dimensional conformal arc planning method, which has been proposed for liver SBRT planning at our center. In this study, we compared the MDCA technique with the RapidArc technique in terms of planning target volume (PTV) coverage and sparing of organs at risk (OARs). The results show that the MDCA technique hasmore » comparable plan quality to RapidArc considering PTV coverage, hot spots, heterogeneity index, and effective liver volume. For the 5 PTVs studied among 4 patients, the MDCA plan, when compared with the RapidArc plan, showed 9% more hot spots, more heterogeneity effect, more sparing of OARs, and lower liver effective volume. The monitor unit (MU) number for the MDCA plan is much lower than for the RapidArc plans. The MDCA plan has the advantages of less planning time, no-collision treatment, and a lower MU number.« less

NOTE: Pre-clinical evaluation of respiratory-gated delivery of volumetric modulated arc therapy with RapidArc

NASA Astrophysics Data System (ADS)

Nicolini, Giorgia; Vanetti, Eugenio; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

2010-06-01

A study was carried out to evaluate the possibility of delivering volumetric modulated arc therapy with the RapidArc technology under respiratory-gated conditions. The experiments were performed in the framework of a non-clinically released environment. Plans of six patients, all realized for a single arc, were used for the experiments. The Real-time Position Management™ (RPM) respiratory gating system from Varian was used to generate gate-open signals of different durations. Arcs were delivered applying the different gates creating sequences of beam-hold/beam-on during the dose delivery: the average number of interruptions for a single arc ranged from 0 to 45. Dose prescription was set to 2 Gy and different gate-open periods of 30, 15 and 5 s to keep gantry speed constant at maximum. 5 Gy and 15 Gy doses were then applied to gate-open signals of 5 and 8 s, respectively, to mimic the most challenging conditions of slow gantry rotation and high-frequency interruptions. The 5 and 15 Gy experiments represent dose conditions of clinical interest for stereotactic treatments. For each patient and gating condition, pre-treatment 2D verification measurements were performed using the PTW-729 array in conjunction with the Octavius phantom (PTW, Freiburg); measurements were performed on different days (one per patient, with the complete setup of phantom and detectors every time), while each gating experiment was repeated seven consecutive times for reproducibility (without a new setup of the measurement equipment). Measurements were compared with dose calculations in the treatment planning system (performed without any gating) to appraise the dosimetric impact of the presence of gating and the eventual dependence from the number of interruptions during a single arc. Analysis of machine-registered log files in terms of average deviations between actual and expected positions (from automatic measurements every 50 ms) resulted in mean ΔMU (monitor units) <0.02% for all gating conditions. Δ(Gantry angle) = 0.38 ± 0.01° for 2 Gy (all gate periods), 0.24 ± 0.01° for 5 Gy, and 0.10 ± 0.01° for 15 Gy deliveries. Average deviations for multileaf collimator (MLC) positions (root mean square over all 120 leaves) were 0.45 ± 0.01 mm for 2 Gy (all gate periods), 0.32 ± 0.01 mm for 5 Gy and 0.14 ± 0.01 mm for 15 Gy. Results in terms of dose measurements confirmed that the application of gating to RapidArc delivery does not affect the quality of the dose delivery. With criteria of ΔD = 3%, DTA = 3 mm, the gamma test was passing in a range of 99 to 100% of the measured points for most of the cases (with maximum number of interruptions of about 20 per arc) and from 97 to 98% for the extreme case of 15 Gy and 8 s gate-open signal (corresponding to almost 50 interruptions per arc). In conclusion, RapidArc delivery proved, in a pre-clinical phase and non-clinically released framework, to be reliable and dosimetrically accurate also when applied in conjunction with gating procedures.

Evaluation of the clinical usefulness of modulated arc treatment

NASA Astrophysics Data System (ADS)

Lee, Young Kyu; Jang, Hong Seok; Kim, Yeon Sil; Choi, Byung Ock; Kang, Young-Nam; Nam, Sang Hee; Park, Hyeong Wook; Kim, Shin Wook; Shin, Hun Joo; Lee, Jae Choon; Kim, Ji Na; Park, Sung Kwang; Kim, Jin Young

2015-07-01

The purpose of this study is to evaluate the clinical usefulness of modulated arc (mARC) treatment techniques. The mARC treatment plans for non-small-cell lung cancer (NSCLC) patients were made in order to verify the clinical usefulness of mARC. A pre-study was conducted to find the best plan condition for mARC treatment, and the usefulness of the mARC treatment plan was evaluated by comparing it with other Arc treatment plans such as tomotherapy and RapidArc plans. In the case of mARC, the optimal condition for the mARC plan was determined by comparing the dosimetric performance of the mARC plans developed by using various parameters, which included the photon energy (6 MV, 10 MV), the optimization point angle (6°- 10°intervals), and the total number of segments (36 - 59 segments). The best dosimetric performance of mARC was observed at a 10 MV photon energy, a point angle 6 degrees, and 59 segments. The treatment plans for the three different techniques were compared by using the following parameters: the conformity index (CI), homogeneity index (HI), the target coverage, the dose to the OARs, the number of monitor units (MU), the beam on time, and the normal tissue complication probability (NTCP). As a result, the three different treatment techniques showed similar target coverages. The mARC plan had the lowest V20 (volume of lung receiving > 20 Gy) and MU per fraction compared with both the RapidArc and the tomotherapy plans. The mARC plan reduced the beam on time as well. Therefore, the results of this study provide satisfactory evidence that the mARC technique can be considered as a useful clinical technique for radiation treatment.

A comprehensive dosimetric evaluation of using RapidArc volumetric‐modulated arc therapy for the treatment of early‐stage nasopharyngeal carcinoma

PubMed Central

Wong, Wicger; Leung, Lucullus H.T.; Yu, Peter K.N.; So, Ronald W.K.; Cheng, Ashley C.K.

2012-01-01

The purpose of this study was to investigate the potential benefits of using triple‐arc volumetric‐intensity modulated arc radiotherapy (RapidArc (RA)) for the treatment of early‐stage nasopharyngeal carcinoma (NPC). A comprehensive evaluation was performed including plan quality, integral doses, and peripheral doses. Twenty cases of stage I or II NPC were selected for this study. Nine‐field sliding window IMRT, double‐arc, and triple‐arc RA treatment plans were compared with respect to target coverage, dose conformity, critical organ sparing, and integral doses. Measurement of peripheral doses was performed using thermoluminescent dosimeters in an anthropomorphic phantom. While similar conformity and target coverage were achieved by the three types of plans, triple‐arc RA produced better sparing of parotid glands and spinal cord than double‐arc RA or IMRT. Double‐arc RA plans produced slightly inferior parotid sparing and dose homogeneity than the other two delivery methods. The monitor units (MU) required for triple‐arc were about 50% less than those of IMRT plans, while there was no significant difference in the required MUs between triple‐arc and double‐arc RA plans. The peripheral dose in triple‐arc RA was found to be 50% less compared to IMRT near abdominal and pelvic region. Triple‐arc RA improves both the plan quality and treatment efficiency compared with IMRT for the treatment of early stage NPC. It has become the preferred choice of treatment delivery method for early stage NPC at our center. PACS numbers: 87.53.Bn, 87.55.D, 87.55.de, 87.55.dk, 87.56.ng PMID:23149781

Comparison of four commercial devices for RapidArc and sliding window IMRT QA

PubMed Central

Chandraraj, Varatharaj; Manickam, Ravikumar; Esquivel, Carlos; Supe, Sanjay S.; Papanikolaou, Nikos

2011-01-01

For intensity‐modulated radiation therapy, evaluation of the measured dose against the treatment planning calculated dose is essential in the context of patient‐specific quality assurance. The complexity of volumetric arc radiotherapy delivery attributed to its dynamic and synchronization nature require new methods and potentially new tools for the quality assurance of such techniques. In the present study, we evaluated and compared the dosimetric performance of EDR2 film and three other commercially available quality assurance devices: IBA I'MatriXX array, PTW Seven29 array and the Delta 4 array. The evaluation of these dosimetric systems was performed for RapidArc and IMRT deliveries using a Varian NovalisTX linear accelerator. The plans were generated using the Varian Eclipse treatment planning system. Our results showed that all four QA techniques yield equivalent results. All patient QAs passed our institutional clinical criteria of gamma index based on a 3% dose difference and 3 mm distance to agreement. In addition, the Bland‐Altman analysis was performed which showed that all the calculated gamma values of all three QA devices were within 5% from those of the film. The results showed that the four QA systems used in this patient‐specific IMRT QA analysis are equivalent. We concluded that the dosimetric systems under investigation can be used interchangeably for routine patient specific QA. PACS numbers: 87.55.Qr, 87.56.Fc

The impacts of dental filling materials on RapidArc treatment planning and dose delivery: Challenges and solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mail, Noor; Al-Ghamdi, S.; Saoudi, A.

Purpose: The presence of high-density material in the oral cavity creates dose perturbation in both downstream and upstream directions at the surfaces of dental filling materials (DFM). In this study, the authors have investigated the effect of DFM on head and neck RapidArc treatment plans and delivery. Solutions are proposed to address (1) the issue of downstream dose perturbation, which might cause target under dosage, and (2) to reduce the upstream dose from DFM which may be the primary source of mucositis. In addition, an investigation of the clinical role of a custom-made plastic dental mold/gutter (PDM) in sparing themore » oral mucosa and tongue reaction is outlined.Methods: The influence of the dental filling artifacts on dose distribution was investigated using a geometrically well-defined head and neck intensity modulated radiation therapy (IMRT) verification phantom (PTW, Freiberg, Germany) with DFM inserts called amalgam, which contained 50% mercury, 25% silver, 14% tin, 8% copper, and 3% other trace metals. Three RapidArc plans were generated in the Varian Eclipse System to treat the oral cavity using the same computer tomography (CT) dataset, including (1) a raw CT image, (2) a streaking artifacts region, which was replaced with a mask of 10 HU, and (3) a 2 cm-thick 6000 HU virtual filter [a volume created in treatment planning system to compensate for beam attenuation, where the thickness of this virtual filter is based on the measured percent depth dose (PDD) data and Eclipse calculation]. The dose delivery for the three plans was verified using Gafchromic-EBT2 film measurements. The custom-made PDM technique to reduce backscatter dose was clinically tested on four head and neck cancer patients (T3, N1, M0) with DFM, two patients with PDM and the other two patients without PDM. The thickness calculation of the PDM toward the mucosa and tongue was purely based on the measured upstream dose. Patients’ with oral mucosal reaction was clinically examined initially and weekly during the course of radiotherapy.Results: For a RapidArc treatment technique, the backscatter dose from the DFM insert was measured to be 9.25 ± 2.17 in the IMRT-verification-phantom. The measured backscatter upstream dose from DFM for a single-field was 22% higher than without the DFM, whereas the downstream dose was lower by 14%. The values of homogeneity index for the plans with and without the application of mask were 0.09 and 0.14, respectively. The calculated mean treatment planning volume (PTV) dose differed from the delivered dose by 13% and was reduced to 2% when using the mask and virtual filter together. A grade 3 mucosa reaction was observed in the control group after 22–24 fractions (44–48 Gy). In contrast, no grade 3 mucositis was observed in the patients wearing the PDM after 25–26 fractions (50–52 Gy).Conclusions: The backscatter from the DFM for a single, parallel-opposed fields, and RapidArc treatment technique was found significant. The application of mask in replacing streaking artifacts can be useful in improving dose homogeneity in the PTV. The use of a virtual filter around the teeth during the planning phase reduces the target underdosage issue in the phantom. Furthermore, a reduction in mucositis is observed in the head and neck patients with the use of PDM.« less

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

PubMed

Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

2013-11-04

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between optimizations with and without using the air cavity correction option.

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

PubMed Central

2012-01-01

Background SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. Methods Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. Results All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. Conclusions Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes. PMID:23216821

Method and apparatus for laser-controlled proton beam radiology

DOEpatents

Johnstone, Carol J.

1998-01-01

A proton beam radiology system provides cancer treatment and proton radiography. The system includes an accelerator for producing an H.sup.- beam and a laser source for generating a laser beam. A photodetachment module is located proximate the periphery of the accelerator. The photodetachment module combines the H.sup.- beam and laser beam to produce a neutral beam therefrom within a subsection of the H.sup.- beam. The photodetachment module emits the neutral beam along a trajectory defined by the laser beam. The photodetachment module includes a stripping foil which forms a proton beam from the neutral beam. The proton beam is delivered to a conveyance segment which transports the proton beam to a patient treatment station. The photodetachment module further includes a laser scanner which moves the laser beam along a path transverse to the cross-section of the H.sup.- beam in order to form the neutral beam in subsections of the H.sup.- beam. As the scanning laser moves across the H.sup.- beam, it similarly varies the trajectory of the proton beam emitted from the photodetachment module and in turn varies the target location of the proton beam upon the patient. Intensity modulation of the proton beam can also be achieved by controlling the output of the laser.

Method and apparatus for laser-controlled proton beam radiology

DOEpatents

Johnstone, C.J.

1998-06-02

A proton beam radiology system provides cancer treatment and proton radiography. The system includes an accelerator for producing an H{sup {minus}} beam and a laser source for generating a laser beam. A photodetachment module is located proximate the periphery of the accelerator. The photodetachment module combines the H{sup {minus}} beam and laser beam to produce a neutral beam therefrom within a subsection of the H{sup {minus}} beam. The photodetachment module emits the neutral beam along a trajectory defined by the laser beam. The photodetachment module includes a stripping foil which forms a proton beam from the neutral beam. The proton beam is delivered to a conveyance segment which transports the proton beam to a patient treatment station. The photodetachment module further includes a laser scanner which moves the laser beam along a path transverse to the cross-section of the H{sup {minus}} beam in order to form the neutral beam in subsections of the H{sup {minus}} beam. As the scanning laser moves across the H{sup {minus}} beam, it similarly varies the trajectory of the proton beam emitted from the photodetachment module and in turn varies the target location of the proton beam upon the patient. Intensity modulation of the proton beam can also be achieved by controlling the output of the laser. 9 figs.

Quality assurance methodology for Varian RapidArc treatment plans

PubMed Central

Cirino, Eileen T.; Xiong, Li; Mower, Herbert W.

2010-01-01

With the commercial introduction of the Varian RapidArc, a new modality for treatment planning and delivery, the need has arisen for consistent and efficient techniques for performing patient‐specific quality assurance (QA) tests. In this paper we present our methodology for a RapidArc treatment plan QA procedure. For our measurements we used a 2D diode array (MapCHECK) embedded at 5 cm water equivalent depth in MapPHAN 5 phantom and an Exradin A16 ion chamber placed in six different positions in a cylindrical homogeneous phantom (QUASAR). We also checked the MUs for the RapidArc plans by using independent software (RadCalc). The agreement between Eclipse calculations and MapCHECK/MapPHAN 5 measurements was evaluated using both absolute distance‐to‐agreement (DTA) and gamma index with 10% dose threshold (TH), 3% dose difference (DD), and 3 mm DTA. The average agreement was 94.4% for the DTA approach and 96.3% for the gamma index approach. In high‐dose areas, the discrepancy between calculations and ion chamber measurements using the QUASAR phantom was within 4.5% for prostate cases. For the RadCalc calculations, we used the average SSD along the arc; however, for some patients the agreement for the MUs obtained with RadCalc versus Eclipse was inadequate (discrepancy>5%). In these cases, the plan was divided into partial arc plans so that RadCalc could perform a better estimation of the MUs. The discrepancy was further reduced to within ~4% using this approach. Regardless of the variation in prescribed dose and location of the treated areas, we obtained very good results for all patients studied in this paper. PACS number: 87.55.Qr

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low‐density media

PubMed Central

Leung, Lucullus H.T.; Yu, Peter K.N.

2013-01-01

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric‐modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no‐air) for RapidArc planning in targets with low‐density media of different sizes and complexities. The performance of PRO10_no‐air and PRO10_air was initially compared using single‐arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple‐arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non‐small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no‐air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low‐density media were present in or adjacent to the target volume, the use of the air cavity correction option in PROIO was shown to be beneficial. For NPC cases or cases for which small volumes of both low‐ and high‐density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between optimizations with and without using the air cavity correction option. PACS number: 87.55.D‐, 87.55.de, 87.56.N‐

Adaptive volumetric modulated arc treatment planning for esophageal cancers using cone beam computed tomography.

PubMed

Sriram, Padmanaban; Syamkumar, S A; Kumar, J Sam Deva; Prabakar, Sukumar; Dhanabalan, Rajasekaran; Vivekanandan, Nagarajan

2012-10-01

To assess the potential of cone beam CT (CBCT) derived adaptive RapidArc treatment for esophageal cancers in reducing the dose to organs at risk (OAR). Ten patients with esophageal cancer were CT scanned in free breathing pattern. The PTV is generated by adding a 3D margin of 1 cm to the CTV as per ICRU 62 recommendations. The double arc RapidArc plan (Clin_RA) was generated for the PTV. Patients were setup using kV orthogonal images and kV-CBCT scan was acquired daily during first week of therapy, then weekly. These images were exported to the Eclipse TPS. The adaptive CTV which includes tumor and involved nodes was delineated in each CBCT image set for the length of the PTV. The composite CTV from first week CBCT was generated using Boolean union operator and 5 mm margin was added circumferentially to generate adaptive PTV (PTV1). Adaptive RapidArc plan (Adap_RA) was generated. NTCP and DVH of the OARs of the two plans were compared. Similarly, PTV2 was generated from weekly CBCT. PTV2 was evaluated for the coverage of 95% isodose of Adap_RA plan. The PTV1 and PTV2 volumes covered by 95% isodose in adaptive plans were 93.51 ± 1.17% and 94.59 ± 1.43% respectively. The lung V(10Gy,)V(20Gy) and mean dose in Adap_RA plan was reduced by 17.43% (p = 0.0012), 34.64% (p = 0.0019) and 16.50% (p = 0.0002) respectively compared to Clin_RA. The Adap_RA plan reduces the heart D(35%) and mean dose by 17.35% (p = 0.0011) and 17.16% (p = 0.0012). No significant reduction in spinal cord and liver doses were observed. NTCP for the lung (0.42% vs. 0.08%) and heart (1.39% vs. 0.090%) was reduced significantly in adaptive plans. The adaptive re-planning strategy based on the first week CBCT dataset significantly reduces the doses and NTCP to OARs. Copyright © 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-E-T-182: Feasibility of Dose Painting by Numbers in Proton Therapy with Contour-Driven Plan Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montero, A Barragan; Differding, S; Lee, J

Purpose: The work aims to 1) prove the feasibility of dose painting by numbers (DPBN) in proton therapy with usual contour-driven plan optimization and 2) compare the achieved plan quality to that of rotational IMRT. Methods: For two patients with head and neck cancers, voxel-by-voxel prescription to the target volume (PTV-PET) was calculated from {sup 18} FDG-PET images and converted to contour-based prescription by defining several sub-contours. Treatments were planned with RayStation (RaySearch Laboratories, Sweden) and proton pencil beam scanning modality. In order to determine the optimal plan parameters to approach the DPBN prescription, the effect of the number ofmore » fields, number of sub-contours and use of range shifter were tested separately on each patient. The number of sub-contours were increased from 3 to 11 while the number of fields were set to 3, 5, 7 and 9. Treatment plans were also optimized on two rotational IMRT systems (TomoTherapy and Varian RapidArc) using previously published guidelines. Results: For both patients, more than 99% of the PTV-PET received at least 95% of the prescribed dose while less than 1% of the PTV-PET received more than 105%, which demonstrates the feasibility of the treatment. Neither the use of a range shifter nor the increase of the number of fields had a significant influence on PTV coverage. Plan quality increased when increasing number of fields up to 7 or 9 and slightly decreased for a bigger number of sub-contours. Good OAR sparing is achieved while keeping high plan quality. Finally, proton therapy achieved significantly better plan quality than rotational IMRT. Conclusion: Voxel-by-voxel prescriptions can be approximated accurately in proton therapy using a contour-driven optimization. Target coverage is nearly insensitive to the number of fields and the use of a range shifter. Finally, plan quality assessment confirmed the superiority of proton therapy compared to rotational IMRT.« less

Angle-dependent modulated spectral peaks of proton beams generated in ultrashort intense laser-solid interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, L. N.; Hu, Z. D.; Zheng, Y.

2014-09-15

Proton acceleration from 4 μm thick aluminum foils irradiated by 30-TW Ti:sapphire laser pulses is investigated using an angle-resolved proton energy spectrometer. We find that a modulated spectral peak at ∼0.82 MeV is presented at 2.5° off the target normal direction. The divergence angle of the modulated zone is 3.8°. Two-dimensional particle-in-cell simulations reveal that self-generated toroidal magnetic field at the rear surface of the target foil is responsible for the modulated spectral feature. The field deflects the low energy protons, resulting in the modulated energy spectrum with certain peaks.

SU-F-P-30: Clinical Assessment of Auto Beam-Hold Triggered by Fiducial Localization During Prostate RapidArc Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atkinson, P; Chen, Q

2016-06-15

Purpose: To assess the clinical efficacy of auto beam hold during prostate RapidArc delivery, triggered by fiducial localization on kV imaging with a Varian True Beam. Methods: Prostate patients with four gold fiducials were candidates in this study. Daily setup was accomplished by aligning to fiducials using orthogonal kV imaging. During RapidArc delivery, a kV image was automatically acquired with a momentary beam hold every 60 degrees of gantry rotation. The position of each fiducial was identified by a search algorithm and compared to a predetermined 1.4 cm diameter target area. Treatment continued if all the fiducials were within themore » target area. If any fiducial was outside the target area the beam hold was not released, and the operators determined if the patient needed re-alignment using the daily setup method. Results: Four patients were initially selected. For three patients, the auto beam hold performed seamlessly. In one instance, the system correctly identified misaligned fiducials, stopped treatment, and the patient was re-positioned. The fourth patient had a prosthetic hip which sometimes blocked the fiducials and caused the fiducial search algorithm to fail. The auto beam hold was disabled for this patient and the therapists manually monitored the fiducial positions during treatment. Average delivery time for a 2-arc fraction was increased by 59 seconds. Phantom studies indicated the dose discrepancy related to multiple beam holds is <0.1%. For a plan with 43 fractions, the additional imaging increased dose by an estimated 68 cGy. Conclusion: Automated intrafraction kV imaging can effectively perform auto beam holds due to patient movement, with the exception of prosthetic hip patients. The additional imaging dose and delivery time are clinically acceptable. It may be a cost-effective alternative to Calypso in RapidArc prostate patient delivery. Further study is warranted to explore its feasibility under various clinical conditions.« less

Comparison of plan quality and delivery time between volumetric arc therapy (RapidArc) and Gamma Knife radiosurgery for multiple cranial metastases.

PubMed

Thomas, Evan M; Popple, Richard A; Wu, Xingen; Clark, Grant M; Markert, James M; Guthrie, Barton L; Yuan, Yu; Dobelbower, Michael C; Spencer, Sharon A; Fiveash, John B

2014-10-01

Volumetric modulated arc therapy (VMAT) has been shown to be feasible for radiosurgical treatment of multiple cranial lesions with a single isocenter. To investigate whether equivalent radiosurgical plan quality and reduced delivery time could be achieved in VMAT for patients with multiple intracranial targets previously treated with Gamma Knife (GK) radiosurgery. We identified 28 GK treatments of multiple metastases. These were replanned for multiarc and single-arc, single-isocenter VMAT (RapidArc) in Eclipse. The prescription for all targets was standardized to 18 Gy. Each plan was normalized for 100% prescription dose to 99% to 100% of target volume. Plan quality was analyzed by target conformity (Radiation Therapy Oncology Group and Paddick conformity indices [CIs]), dose falloff (area under the dose-volume histogram curve), as well as the V4.5, V9, V12, and V18 isodose volumes. Other end points included beam-on and treatment time. Compared with GK, multiarc VMAT improved median plan conformity (CIVMAT = 1.14, CIGK = 1.65; P < .001) with no significant difference in median dose falloff (P = .269), 12 Gy isodose volume (P = .500), or low isodose spill (P = .49). Multiarc VMAT plans were associated with markedly reduced treatment time. A predictive model of the 12 Gy isodose volume as a function of tumor number and volume was also developed. For multiple target stereotactic radiosurgery, 4-arc VMAT produced clinically equivalent conformity, dose falloff, 12 Gy isodose volume, and low isodose spill, and reduced treatment time compared with GK. Because of its similar plan quality and increased delivery efficiency, single-isocenter VMAT radiosurgery may constitute an attractive alternative to multi-isocenter radiosurgery for some patients.

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx.

PubMed

Ahamed, Shabbir; Singh, Navin; Gudipudi, Deleep; Mulinti, Suneetha; Talluri, Anil; Soubhagya, Bhudevi; Sresty, Madhusudhana

2017-03-01

To quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc. Ten cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using "Intermediate dose" feature and "MU tool" to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA). With increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6-34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5Gy was higher for baseline plans while lower between 20 and 35Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans. Baseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Characterization of heteronuclear decoupling through proton spin dynamics in solid-state nuclear magnetic resonance spectroscopy

NASA Astrophysics Data System (ADS)

De Paëpe, Gaël; Eléna, Bénédicte; Emsley, Lyndon

2004-08-01

The work presented here aims at understanding the performance of phase modulated heteronuclear decoupling sequences such as Cosine Modulation or Two Pulse Phase Modulation. To that end we provide an analytical description of the intrinsic behavior of Cosine Modulation decoupling with respect to radio-frequency-inhomogeneity and the proton-proton dipolar coupling network. We discover through a Modulation Frame average Hamiltonian analysis that best decoupling is obtained under conditions where the heteronuclear interactions are removed but notably where homonuclear couplings are recoupled at a homonuclear Rotary Resonance (HORROR) condition in the Modulation Frame. These conclusions are supported by extensive experimental investigations, and notably through the introduction of proton nutation experiments to characterize spin dynamics in solids under decoupling conditions. The theoretical framework presented in this paper allows the prediction of the optimum parameters for a given set of experimental conditions.

Indirect self-modulation instability measurement concept for the AWAKE proton beam

NASA Astrophysics Data System (ADS)

Turner, M.; Petrenko, A.; Biskup, B.; Burger, S.; Gschwendtner, E.; Lotov, K. V.; Mazzoni, S.; Vincke, H.

2016-09-01

AWAKE, the Advanced Proton-Driven Plasma Wakefield Acceleration Experiment, is a proof-of-principle R&D experiment at CERN using a 400 GeV / c proton beam from the CERN SPS (longitudinal beam size σz = 12 cm) which will be sent into a 10 m long plasma section with a nominal density of ≈ 7 ×1014 atoms /cm3 (plasma wavelength λp = 1.2 mm). In this paper we show that by measuring the time integrated transverse profile of the proton bunch at two locations downstream of the AWAKE plasma, information about the occurrence of the self-modulation instability (SMI) can be inferred. In particular we show that measuring defocused protons with an angle of 1 mrad corresponds to having electric fields in the order of GV/m and fully developed self-modulation of the proton bunch. Additionally, by measuring the defocused beam edge of the self-modulated bunch, information about the growth rate of the instability can be extracted. If hosing instability occurs, it could be detected by measuring a non-uniform defocused beam shape with changing radius. Using a 1 mm thick Chromox scintillation screen for imaging of the self-modulated proton bunch, an edge resolution of 0.6 mm and hence an SMI saturation point resolution of 1.2 m can be achieved.

A preliminary study on the use of FX-Glycine gel and an in-house optical cone beam CT readout for IMRT and RapidArc verification

NASA Astrophysics Data System (ADS)

Ravindran, Paul B.; Ebenezer, Suman Babu S.; Winfred, Michael Raj; Amalan, S.

2017-05-01

The radiochromic FX gel with Optical CT readout has been investigated by several authors and has shown promising results for 3D dosimetry. One of the applications of the gel dosimeters is their use in 3D dose verification for IMRT and RapidArc quality assurance. Though polymer gel has been used successfully for clinical dose verification, the use of FX gel for clinical dose verification with optical cone beam CT needs further validation. In this work, we have used FX gel and an in- house optical readout system for gamma analysis between the dose matrices of measured dose distribution and a treatment planning system (TPS) calculated dose distribution for a few test cases.

Gate modulation of proton transport in a nanopore.

PubMed

Mei, Lanju; Yeh, Li-Hsien; Qian, Shizhi

2016-03-14

Proton transport in confined spaces plays a crucial role in many biological processes as well as in modern technological applications, such as fuel cells. To achieve active control of proton conductance, we investigate for the first time the gate modulation of proton transport in a pH-regulated nanopore by a multi-ion model. The model takes into account surface protonation/deprotonation reactions, surface curvature, electroosmotic flow, Stern layer, and electric double layer overlap. The proposed model is validated by good agreement with the existing experimental data on nanopore conductance with and without a gate voltage. The results show that the modulation of proton transport in a nanopore depends on the concentration of the background salt and solution pH. Without background salt, the gated nanopore exhibits an interesting ambipolar conductance behavior when pH is close to the isoelectric point of the dielectric pore material, and the net ionic and proton conductance can be actively regulated with a gate voltage as low as 1 V. The higher the background salt concentration, the lower is the performance of the gate control on the proton transport.

Fan-beam intensity modulated proton therapy.

PubMed

Hill, Patrick; Westerly, David; Mackie, Thomas

2013-11-01

This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems. Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.

Easy-Going On-Spectrometer Optimisation of Phase Modulated Homonuclear Decoupling Sequences in Solid-State NMR

NASA Astrophysics Data System (ADS)

Grimminck, Dennis L. A. G.; Vasa, Suresh K.; Meerts, W. Leo; Kentgens, P. M.

2011-06-01

A global optimisation scheme for phase modulated proton homonuclear decoupling sequences in solid-state NMR is presented. Phase modulations, parameterised by DUMBO Fourier coefficients, were optimized using a Covariance Matrix Adaptation Evolution Strategies algorithm. Our method, denoted EASY-GOING homonuclear decoupling, starts with featureless spectra and optimises proton-proton decoupling, during either proton or carbon signal detection. On the one hand, our solutions closely resemble (e)DUMBO for moderate sample spinning frequencies and medium radio-frequency (rf) field strengths. On the other hand, the EASY-GOING approach resulted in a superior solution, achieving significantly better resolved proton spectra at very high 680 kHz rf field strength. N. Hansen, and A. Ostermeier. Evol. Comput. 9 (2001) 159-195 B. Elena, G. de Paepe, L. Emsley. Chem. Phys. Lett. 398 (2004) 532-538

Marvin: an anatomical phantom for dosimetric evaluation of complex radiotherapy of the head and neck.

PubMed

Aitkenhead, A H; Rowbottom, C G; Mackay, R I

2013-10-07

We report on the design of Marvin, a Model Anatomy for Radiotherapy Verification and audit In the head and Neck and present results demonstrating its use in the development of the Elekta volumetric modulated arc therapy (VMAT) technique at the Christie, and in the audit of TomoTherapy and Varian RapidArc at other institutions. The geometry of Marvin was generated from CT datasets of eight male and female patients lying in the treatment position, with removable inhomogeneities modelling the sinuses and mandible. A modular system allows the phantom to be used with a range of detectors, with the locations of the modules being based on an analysis of a range of typical treatment plans (27 in total) which were mapped onto the phantom geometry. Results demonstrate the use of Gafchromic EBT2/EBT3 film for measurement of relative dose in a plane through the target and organs-at-risk, and the use of a small-volume ionization chamber for measurement of absolute dose in the target and spinal cord. Measurements made during the development of the head and neck VMAT protocol at the Christie quantified the improvement in plan delivery resulting from the installation of the Elekta Integrity upgrade (which permits an effectively continuously variable dose rate), with plans delivered before and after the upgrade having 88.5 ± 9.4% and 98.0 ± 2.2% respectively of points passing a gamma analysis (at 4%, 4 mm, global). Audits of TomoTherapy and Varian RapidArc neck techniques at other institutions showed a similar quality of plan delivery as for post-Integrity Elekta VMAT: film measurements for both techniques had >99% of points passing a gamma analysis at the clinical criteria of 4%, 4 mm, global, and >95% of points passing at tighter criteria of 3%, 3 mm, global; and absolute dose measurements in the PTV and spinal cord were within 1.5% and 3.5% of the planned doses respectively for both techniques. The results demonstrate that Marvin is an efficient and effective means of assessing the quality of delivery of complex radiotherapy in the head and neck, and is a useful tool to assist development and audit of these techniques.

Marvin: an anatomical phantom for dosimetric evaluation of complex radiotherapy of the head and neck

NASA Astrophysics Data System (ADS)

Aitkenhead, A. H.; Rowbottom, C. G.; Mackay, R. I.

2013-10-01

We report on the design of Marvin, a Model Anatomy for Radiotherapy Verification and audit In the head and Neck and present results demonstrating its use in the development of the Elekta volumetric modulated arc therapy (VMAT) technique at the Christie, and in the audit of TomoTherapy and Varian RapidArc at other institutions. The geometry of Marvin was generated from CT datasets of eight male and female patients lying in the treatment position, with removable inhomogeneities modelling the sinuses and mandible. A modular system allows the phantom to be used with a range of detectors, with the locations of the modules being based on an analysis of a range of typical treatment plans (27 in total) which were mapped onto the phantom geometry. Results demonstrate the use of Gafchromic EBT2/EBT3 film for measurement of relative dose in a plane through the target and organs-at-risk, and the use of a small-volume ionization chamber for measurement of absolute dose in the target and spinal cord. Measurements made during the development of the head and neck VMAT protocol at the Christie quantified the improvement in plan delivery resulting from the installation of the Elekta Integrity upgrade (which permits an effectively continuously variable dose rate), with plans delivered before and after the upgrade having 88.5 ± 9.4% and 98.0 ± 2.2% respectively of points passing a gamma analysis (at 4%, 4 mm, global). Audits of TomoTherapy and Varian RapidArc neck techniques at other institutions showed a similar quality of plan delivery as for post-Integrity Elekta VMAT: film measurements for both techniques had >99% of points passing a gamma analysis at the clinical criteria of 4%, 4 mm, global, and >95% of points passing at tighter criteria of 3%, 3 mm, global; and absolute dose measurements in the PTV and spinal cord were within 1.5% and 3.5% of the planned doses respectively for both techniques. The results demonstrate that Marvin is an efficient and effective means of assessing the quality of delivery of complex radiotherapy in the head and neck, and is a useful tool to assist development and audit of these techniques.

A critical evaluation of the PTW 2D‐ARRAY seven29 and OCTAVIUS II phantom for IMRT and VMAT verification

PubMed Central

Adams, Elizabeth J.; Jordan, Thomas J.; Clark, Catharine H.; Nisbet, Andrew

2013-01-01

Quality assurance (QA) for intensity‐ and volumetric‐modulated radiotherapy (IMRT and VMAT) has evolved substantially. In recent years, various commercial 2D and 3D ionization chamber or diode detector arrays have become available, allowing for absolute verification with near real time results, allowing for streamlined QA. However, detector arrays are limited by their resolution, giving rise to concerns about their sensitivity to errors. Understanding the limitations of these devices is therefore critical. In this study, the sensitivity and resolution of the PTW 2D‐ARRAY seven29 and OCTAVIUS II phantom combination was comprehensively characterized for use in dynamic sliding window IMRT and RapidArc verification. Measurement comparisons were made between single acquisition and a multiple merged acquisition techniques to improve the effective resolution of the 2D‐ARRAY, as well as comparisons against GAFCHROMIC EBT2 film and electronic portal imaging dosimetry (EPID). The sensitivity and resolution of the 2D‐ARRAY was tested using two gantry angle 0° modulated test fields. Deliberate multileaf collimator (MLC) errors of 1, 2, and 5 mm and collimator rotation errors were inserted into IMRT and RapidArc plans for pelvis and head & neck sites, to test sensitivity to errors. The radiobiological impact of these errors was assessed to determine the gamma index passing criteria to be used with the 2D‐ARRAY to detect clinically relevant errors. For gamma index distributions, it was found that the 2D‐ARRAY in single acquisition mode was comparable to multiple acquisition modes, as well as film and EPID. It was found that the commonly used gamma index criteria of 3% dose difference or 3 mm distance to agreement may potentially mask clinically relevant errors. Gamma index criteria of 3%/2 mm with a passing threshold of 98%, or 2%/2 mm with a passing threshold of 95%, were found to be more sensitive. We suggest that the gamma index passing thresholds may be used for guidance, but also should be combined with a visual inspection of the gamma index distribution and calculation of the dose difference to assess whether there may be a clinical impact in failed regions. PACS numbers: 87.55.Qr, 87.56.Fc PMID:24257288

Proton therapy in clinical practice

PubMed Central

Liu, Hui; Chang, Joe Y.

2011-01-01

Radiation dose escalation and acceleration improves local control but also increases toxicity. Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients. Compared with photon therapy, proton therapy spares more critical structures due to its unique physics. The physical properties of a proton beam make it ideal for clinical applications. By modulating the Bragg peak of protons in energy and time, a conformal radiation dose with or without intensity modulation can be delivered to the target while sparing the surrounding normal tissues. Thus, proton therapy is ideal when organ preservation is a priority. However, protons are more sensitive to organ motion and anatomy changes compared with photons. In this article, we review practical issues of proton therapy, describe its image-guided treatment planning and delivery, discuss clinical outcome for cancer patients, and suggest challenges and the future development of proton therapy. PMID:21527064

Design and application of 3D-printed stepless beam modulators in proton therapy

NASA Astrophysics Data System (ADS)

Lindsay, C.; Kumlin, J.; Martinez, D. M.; Jirasek, A.; Hoehr, C.

2016-06-01

A new method for the design of stepless beam modulators for proton therapy is described and verified. Simulations of the classic designs are compared against the stepless method for various modulation widths which are clinically applicable in proton eye therapy. Three modulator wheels were printed using a Stratasys Objet30 3D printer. The resulting depth dose distributions showed improved uniformity over the classic stepped designs. Simulated results imply a possible improvement in distal penumbra width; however, more accurate measurements are needed to fully verify this effect. Lastly, simulations were done to model bio-equivalence to Co-60 cell kill. A wheel was successfully designed to flatten this metric.

Wave-Coupled Millimeter-Wave Electro-Optic Techniques

DTIC Science & Technology

2001-03-01

This report details results on two antenna-coupled millimeter-wave electro - optic modulators, the slot-vee antenna-coupled modulator and a 94 GHz...study of the effects of velocity mismatch on linearized electro - optic modulators was made and the results published. A key result was that directional...drift in electro - optic modulators was made and protons were determined to be the cause. Several inventions were made to reduce or eliminate proton-caused bias drift.

AWAKE readiness for the study of the seeded self-modulation of a 400 GeV proton bunch

NASA Astrophysics Data System (ADS)

Muggli, P.; Adli, E.; Apsimon, R.; Asmus, F.; Baartman, R.; Bachmann, A.-M.; Barros Marin, M.; Batsch, F.; Bauche, J.; Berglyd Olsen, V. K.; Bernardini, M.; Biskup, B.; Blanco Vinuela, E.; Boccardi, A.; Bogey, T.; Bohl, T.; Bracco, C.; Braunmuller, F.; Burger, S.; Burt, G.; Bustamante, S.; Buttenschön, B.; Butterworth, A.; Caldwell, A.; Cascella, M.; Chevallay, E.; Chung, M.; Damerau, H.; Deacon, L.; Dexter, A.; Dirksen, P.; Doebert, S.; Farmer, J.; Fedosseev, V.; Feniet, T.; Fior, G.; Fiorito, R.; Fonseca, R.; Friebel, F.; Gander, P.; Gessner, S.; Gorgisyan, I.; Gorn, A. A.; Grulke, O.; Gschwendtner, E.; Guerrero, A.; Hansen, J.; Hessler, C.; Hofle, W.; Holloway, J.; Hüther, M.; Ibison, M.; Islam, M. R.; Jensen, L.; Jolly, S.; Kasim, M.; Keeble, F.; Kim, S.-Y.; Kraus, F.; Lasheen, A.; Lefevre, T.; LeGodec, G.; Li, Y.; Liu, S.; Lopes, N.; Lotov, K. V.; Martyanov, M.; Mazzoni, S.; Medina Godoy, D.; Mete, O.; Minakov, V. A.; Mompo, R.; Moody, J.; Moreira, M. T.; Mitchell, J.; Mutin, C.; Norreys, P.; Öz, E.; Ozturk, E.; Pauw, W.; Pardons, A.; Pasquino, C.; Pepitone, K.; Petrenko, A.; Pitmann, S.; Plyushchev, G.; Pukhov, A.; Rieger, K.; Ruhl, H.; Schmidt, J.; Shalimova, I. A.; Shaposhnikova, E.; Sherwood, P.; Silva, L.; Sosedkin, A. P.; Speroni, R.; Spitsyn, R. I.; Szczurek, K.; Thomas, J.; Tuev, P. V.; Turner, M.; Verzilov, V.; Vieira, J.; Vincke, H.; Welsch, C. P.; Williamson, B.; Wing, M.; Xia, G.; Zhang, H.; AWAKE Collaboration

2018-01-01

AWAKE is a proton-driven plasma wakefield acceleration experiment. We show that the experimental setup briefly described here is ready for systematic study of the seeded self-modulation of the 400 GeV proton bunch in the 10 m long rubidium plasma with density adjustable from 1 to 10× {10}14 cm-3. We show that the short laser pulse used for ionization of the rubidium vapor propagates all the way along the column, suggesting full ionization of the vapor. We show that ionization occurs along the proton bunch, at the laser time and that the plasma that follows affects the proton bunch.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beltran, C; Kamal, H

Purpose: To provide a multicriteria optimization algorithm for intensity modulated radiation therapy using pencil proton beam scanning. Methods: Intensity modulated radiation therapy using pencil proton beam scanning requires efficient optimization algorithms to overcome the uncertainties in the Bragg peaks locations. This work is focused on optimization algorithms that are based on Monte Carlo simulation of the treatment planning and use the weights and the dose volume histogram (DVH) control points to steer toward desired plans. The proton beam treatment planning process based on single objective optimization (representing a weighted sum of multiple objectives) usually leads to time-consuming iterations involving treatmentmore » planning team members. We proved a time efficient multicriteria optimization algorithm that is developed to run on NVIDIA GPU (Graphical Processing Units) cluster. The multicriteria optimization algorithm running time benefits from up-sampling of the CT voxel size of the calculations without loss of fidelity. Results: We will present preliminary results of Multicriteria optimization for intensity modulated proton therapy based on DVH control points. The results will show optimization results of a phantom case and a brain tumor case. Conclusion: The multicriteria optimization of the intensity modulated radiation therapy using pencil proton beam scanning provides a novel tool for treatment planning. Work support by a grant from Varian Inc.« less

SU-F-J-214: Dose Reduction by Spatially Optimized Image Quality Via Fluence Modulated Proton CT (FMpCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Angelis, L; Landry, G; Dedes, G

Purpose: Proton CT (pCT) is a promising imaging modality for reducing range uncertainty in image-guided proton therapy. Range uncertainties partially originate from X-ray CT number conversion to stopping power ratio (SPR) and are limiting the exploitation of the full potential of proton therapy. In this study we explore the concept of spatially dependent fluence modulated proton CT (FMpCT), for achieving optimal image quality in a clinical region of interest (ROI), while reducing significantly the imaging dose to the patient. Methods: The study was based on simulated ideal pCT using pencil beam (PB) scanning. A set of 250 MeV protons PBsmore » was used to create 360 projections of a cylindrical water phantom and a head and neck cancer patient. The tomographic images were reconstructed using a filtered backprojection (FBP) as well as an iterative algorithm (ITR). Different fluence modulation levels were investigated and their impact on the image was quantified in terms of SPR accuracy as well as noise within and outside selected ROIs, as a function of imaging dose. The unmodulated image served as reference. Results: Both FBP reconstruction and ITR without total variation (TV) yielded image quality in the ROIs similar to the reference images, for modulation down to 0.1 of the full proton fluence. The average dose was reduced by 75% for the water phantom and by 40% for the patient. FMpCT does not improve the noise for ITR with TV and modulation 0.1. Conclusion: This is the first work proposing and investigating FMpCT for producing optimal image quality for treatment planning and image guidance, while simultaneously reducing imaging dose. Future work will address spatial resolution effects and the impact of FMpCT on the quality of proton treatment plans for a prototype pCT scanner capable of list mode data acquisition. Acknowledgement: DFG-MAP DFG - Munich-Centre for Advanced Photonics (MAP)« less

Summary of Proton Test on the Actel A1280A at Indiana University

NASA Technical Reports Server (NTRS)

Katz, Richard; LaBel, K.

1998-01-01

A summary of tests performed at the Indiana University Cycl,oltron Facility, on the Actel A1280A circuit device is described. The intent of the study was to investigate the proton response of the hard-wired S-Module flip-flops with a large sample size. This device is sensitive to protons for S-Modules. The device's performance in the test is shown in graphs, and was typical for devices of this class.

Incorporating partial shining effects in proton pencil-beam dose calculation

NASA Astrophysics Data System (ADS)

Li, Yupeng; Zhang, Xiaodong; Fwu Lii, Ming; Sahoo, Narayan; Zhu, Ron X.; Gillin, Michael; Mohan, Radhe

2008-02-01

A range modulator wheel (RMW) is an essential component in passively scattered proton therapy. We have observed that a proton beam spot may shine on multiple steps of the RMW. Proton dose calculation algorithms normally do not consider the partial shining effect, and thus overestimate the dose at the proximal shoulder of spread-out Bragg peak (SOBP) compared with the measurement. If the SOBP is adjusted to better fit the plateau region, the entrance dose is likely to be underestimated. In this work, we developed an algorithm that can be used to model this effect and to allow for dose calculations that better fit the measured SOBP. First, a set of apparent modulator weights was calculated without considering partial shining. Next, protons spilled from the accelerator reaching the modulator wheel were simplified as a circular spot of uniform intensity. A weight-splitting process was then performed to generate a set of effective modulator weights with the partial shining effect incorporated. The SOBPs of eight options, which are used to label different combinations of proton-beam energy and scattering devices, were calculated with the generated effective weights. Our algorithm fitted the measured SOBP at the proximal and entrance regions much better than the ones without considering partial shining effect for all SOBPs of the eight options. In a prostate patient, we found that dose calculation without considering partial shining effect underestimated the femoral head and skin dose.

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron.

PubMed

Jones, Kevin C; Vander Stappen, François; Bawiec, Christopher R; Janssens, Guillaume; Lewin, Peter A; Prieels, Damien; Solberg, Timothy D; Sehgal, Chandra M; Avery, Stephen

2015-12-01

To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be on the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.

Correction of stopping power and LET quenching for radiophotoluminescent glass dosimetry in a therapeutic proton beam

NASA Astrophysics Data System (ADS)

Chang, Weishan; Koba, Yusuke; Katayose, Tetsurou; Yasui, Keisuke; Omachi, Chihiro; Hariu, Masatsugu; Saitoh, Hidetoshi

2017-12-01

To measure the absorbed dose to water D w in proton beams using a radiophotoluminescent glass dosimeter (RGD), a method with the correction for the change of the mass stopping power ratio (SPR) and the linear energy transfer (LET) dependence of radiophotoluminescent efficiency \\varepsilon LETRGD is proposed. The calibration coefficient in terms of D w for RGDs (GD-302M, Asahi Techno Glass) was obtained using a 60Co γ-ray. The SPR of water to the RGD was calculated by Monte Carlo simulation, and \\varepsilon LETRGD was investigated experimentally using a 70 MeV proton beam. For clinical usage, the residual range R res was used as a quality index to determine the correction factor for the beam quality kQ,{{Q0}}RGD and the LET quenching effect of the RGD kLETRGD . The proposed method was evaluated by measuring D w at different depths in a 200 MeV proton beam. For both non-modulated and modulated proton beams, kQ,{{Q0}}RGD decreases rapidly where R res is less than 4 cm. The difference in kQ,{{Q0}}RGD between a non-modulated and a modulated proton beam is less than 0.5% for the R res range from 0 cm to 22 cm. \\varepsilon LETRGD decreases rapidly at a LET range from 1 to 2 keV µm-1. In the evaluation experiments, D w using RGDs, Dw,QRGD showed good agreement with that obtained using an ionization chamber and the relative difference was within 3% where R res was larger than 1 cm. The uncertainty budget for Dw,QRGD in a proton beam was estimated to investigate the potential of RGD postal dosimetry in proton therapy. These results demonstrate the feasibility of RGD dosimetry in a therapeutic proton beam and the general versatility of the proposed method. In conclusion, the proposed methodology for RGDs in proton dosimetry is applicable where R res  >  1 cm and the RGD is feasible as a postal audit dosimeter for proton therapy.

Epithelioid hemangioendothelioma of the spine treated with RapidArc volumetric-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy, Jean-Baptiste; Trone, Jane-Chloé; Chargari, Cyrus

2014-10-01

Radiotherapy for epithelioid hemangioendothelioma (EHE) using volumetric intensity-modulated arc radiotherapy (VMAT). A 48-year-old woman was referred for curative irradiation of a vertebral EHE after failure of surgery. A comparison between VMAT and conventional conformal tridimensional (3D) dosimetry was performed and potential advantage of VMAT for sparing critical organs from irradiation's side effects was discussed. The total delivered dose on the planning target volume was 54 Gy in 27 fractions. The patient was finally treated with VMAT. The tolerance was excellent. There was no acute toxicity, including no increase in pain. With a follow-up of 18 months, no delayed toxicity wasmore » reported. The clinical response consisted of a decrease in the dorsal pain. The D{sub max} for the spinal cord was reduced from 55 Gy (3D-radiotherapy [RT]) (which would be an unacceptable dose to the spine because of the risk of myelopathy) to 42.8 Gy (VMAT), which remains below the recommended dose threshold (45 Gy). The dose delivered to 20% of organ volume (D{sub 20}) was reduced from 47 Gy (3D-RT) to 3 Gy (VMAT) for the spinal cord. The study shows that VMAT allows the delivery of curative treatment for vertebral EHEs because of critical organ sparing.« less

Abscisic acid accumulation modulates auxin transport in the root tip to enhance proton secretion for maintaining root growth under moderate water stress.

PubMed

Xu, Weifeng; Jia, Liguo; Shi, Weiming; Liang, Jiansheng; Zhou, Feng; Li, Qianfeng; Zhang, Jianhua

2013-01-01

Maintenance of root growth is essential for plant adaptation to soil drying. Here, we tested the hypothesis that auxin transport is involved in mediating ABA's modulation by activating proton secretion in the root tip to maintain root growth under moderate water stress. Rice and Arabidopsis plants were raised under a hydroponic system and subjected to moderate water stress (-0.47 MPa) with polyethylene glycol (PEG). ABA accumulation, auxin transport and plasma membrane H(+)-ATPase activity at the root tip were monitored in addition to the primary root elongation and root hair density. We found that moderate water stress increases ABA accumulation and auxin transport in the root apex. Additionally, ABA modulation is involved in the regulation of auxin transport in the root tip. The transported auxin activates the plasma membrane H(+)-ATPase to release more protons along the root tip in its adaption to moderate water stress. The proton secretion in the root tip is essential in maintaining or promoting primary root elongation and root hair development under moderate water stress. These results suggest that ABA accumulation modulates auxin transport in the root tip, which enhances proton secretion for maintaining root growth under moderate water stress. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Cosmogenic-nuclide production by primary cosmic-ray protons

NASA Technical Reports Server (NTRS)

Reedy, R. C.

1985-01-01

The production rates of cosmogenic nuclides were calculated for the primary protons in the galactic and solar cosmic rays. At 1 AU, the long-term average fluxes of solar protons usually produce many more atoms of cosmogenic nuclide than the primary protons in the galactic cosmic rays (GCR). Because the particle fluxes inside meteorites and other large objects in space include many secondary neutrons, the production rates and ratios inside large objects are often very different from those by just the primary GCR protons. It is possible to determine if a small object, was small in space or broken from a meteorite. Because heliospherical modulation and other interactions change the GCR particle spectrum, the production of cosmogenic nuclides by the GCR particles outside the heliosphere will be different from that by modulated GCR primaries.

Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M., E-mail: smacdonald@partners.or; Trofimov, Alexei; Safai, Sairos

Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treatedmore » with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.« less

Distinct Modulations of Human Capsaicin Receptor by Protons and Magnesium through Different Domains*

PubMed Central

Wang, Shu; Poon, Kinning; Oswald, Robert E.; Chuang, Huai-hu

2010-01-01

The capsaicin receptor (TRPV1) is a nonselective cation channel that integrates multiple painful stimuli, including capsaicin, protons, and heat. Protons facilitate the capsaicin- and heat-induced currents by decreasing thermal threshold or increasing agonist potency for TRPV1 activation (Tominaga, M., Caterina, M. J., Malmberg, A. B., Rosen, T. A., Gilbert, H., Skinner, K., Raumann, B. E., Basbaum, A. I., and Julius, D. (1998) Neuron 21, 531–543). In the presence of saturating capsaicin, rat TRPV1 (rTRPV1) reaches full activation, with no further stimulation by protons. Human TRPV1 (hTRPV1), a species ortholog with high homology to rTRPV1, is potentiated by extracellular protons and magnesium, even at saturating capsaicin. We investigated the structural basis for protons and magnesium modulation of fully capsaicin-bound human receptors. By analysis of chimeric channels between hTRPV1 and rTRPV1, we found that transmembrane domain 1–4 (TM1–4) of TRPV1 determines whether protons can further open the fully capsaicin-bound receptors. Mutational analysis identified a titratable glutamate residue (Glu-536) in the linker between TM3 and TM4 critical for further stimulation of fully liganded hTRPV1. In contrast, hTRPV1 TM5–6 is required for magnesium augmentation of capsaicin efficacy. Our results demonstrate that capsaicin efficacy of hTRPV1 correlates with the extracellular ion milieu and unravel the relevant structural basis of modulation by protons and magnesium. PMID:20145248

Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue.

PubMed

Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Evens, Andrew M; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin

2015-09-01

Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Construction of the Zeus forward/rear calorimeter modules at NIKHEF

NASA Astrophysics Data System (ADS)

Blankers, R.; Engelen, J.; Geerinck, H.; Homma, J.; Hunck, P.; Dekoning, N.; Kooijman, P.; Korporaal, A.; Loos, R.; Straver, J.

1990-07-01

The design and assembly procedure of the FCAL/RCAL (Forward (in proton direction) Calorimeter/Rear (in electron direction) Calorimeter) of the Zeus detector to study electron proton interactions at Desy, Hamburg (Germany, F.R.) are detailed. The main components of the modules are described: steel C-frame which provides the overall mechanical module structure; a stack of depleted uranium plates and scintillator plates; wavelength shifter material, mounted in cassettes for the readout of the scintillator light; stainless steel straps which compress the stack and fix it to the C-frame. Finite element techniques for module force calculations are outlined. The module assembly and transport and calibration tools are described.

A quantitative investigation of the solar modulation of cosmic-ray protons and helium nuclei. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Garrard, T. L.

1972-01-01

The differential energy spectra of cosmic ray protons and He nuclei were measured at energies up to 315 MeV/nucleon using balloon-borne and satellite-borne instruments. These spectra are presented for solar quiet times for the years 1966 through 1970. The data analysis is verified by extensive accelerator calibrations of the detector systems and by calculations and measurements of the production of secondary protons in the atmosphere. The spectra of protons and He nuclei in this energy range are dominated by the solar modulation of the local interstellar spectra. Numerical solutions to the transport equation are presented for a wide range of parameters.

MODULATION OF GALACTIC ELECTRONS IN THE HELIOSPHERE DURING THE UNUSUAL SOLAR MINIMUM OF 2006–2009: A MODELING APPROACH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Potgieter, M. S.; Vos, E. E.; Munini, R.

The last solar minimum activity period, and the consequent minimum modulation conditions for cosmic rays, was unusual. The highest levels of Galactic protons were recorded at Earth in late 2009 in contrast to expectations. A comprehensive model was used to study the proton modulation for the period from 2006 to 2009 in order to determine what basic processes were responsible for solar modulation during this period and why it differs from proton modulation during previous solar minimum modulation periods. This established model is now applied to studying the solar modulation of electron spectra as observed for 80 MeV–30 GeV bymore » the PAMELA space detector from mid-2006 to the end of 2009. Over this period the heliospheric magnetic field had decreased significantly until the end of 2009 while the waviness of the heliospheric current sheet decreased moderately and the observed electron spectra increased by a factor of ∼1.5 at 1.0 GeV to ∼3.5 at 100 MeV. In order to reproduce the modulation evident from seven consecutive semesters, the diffusion coefficients had to increase moderately while maintaining the basic rigidity dependence. It is confirmed that the main diffusion coefficients are independent of rigidity below ∼0.5 GV, while the drift coefficient had to be reduced below this value. The 2006–2009 solar minimum epoch indeed was different than previously observed minima, at least since the beginning of the space exploration era. This period could be called “diffusion-dominated” as was also found for the modulation of protons.« less

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Kevin C.; Solberg, Timothy D.; Avery, Stephen, E-mail: Stephen.Avery@uphs.upenn.edu

Purpose: To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. Methods: An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. Results: The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be onmore » the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. Conclusions: The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.« less

Time-resolved imaging of prompt-gamma rays for proton range verification using a knife-edge slit camera based on digital photon counters

NASA Astrophysics Data System (ADS)

Cambraia Lopes, Patricia; Clementel, Enrico; Crespo, Paulo; Henrotin, Sebastien; Huizenga, Jan; Janssens, Guillaume; Parodi, Katia; Prieels, Damien; Roellinghoff, Frauke; Smeets, Julien; Stichelbaut, Frederic; Schaart, Dennis R.

2015-08-01

Proton range monitoring may facilitate online adaptive proton therapy and improve treatment outcomes. Imaging of proton-induced prompt gamma (PG) rays using a knife-edge slit collimator is currently under investigation as a potential tool for real-time proton range monitoring. A major challenge in collimated PG imaging is the suppression of neutron-induced background counts. In this work, we present an initial performance test of two knife-edge slit camera prototypes based on arrays of digital photon counters (DPCs). PG profiles emitted from a PMMA target upon irradiation with a 160 MeV proton pencil beams (about 6.5   ×   109 protons delivered in total) were measured using detector modules equipped with four DPC arrays coupled to BGO or LYSO : Ce crystal matrices. The knife-edge slit collimator and detector module were placed at 15 cm and 30 cm from the beam axis, respectively, in all cases. The use of LYSO : Ce enabled time-of-flight (TOF) rejection of background events, by synchronizing the DPC readout electronics with the 106 MHz radiofrequency signal of the cyclotron. The signal-to-background (S/B) ratio of 1.6 obtained with a 1.5 ns TOF window and a 3 MeV-7 MeV energy window was about 3 times higher than that obtained with the same detector module without TOF discrimination and 2 times higher than the S/B ratio obtained with the BGO module. Even 1 mm shifts of the Bragg peak position translated into clear and consistent shifts of the PG profile if TOF discrimination was applied, for a total number of protons as low as about 6.5   ×   108 and a detector surface of 6.6 cm  ×  6.6 cm.

Recent advances in intensity modulated radiotherapy and proton therapy for esophageal cancer.

PubMed

Xi, Mian; Lin, Steven H

2017-07-01

Radiotherapy is an important component of the standard of care for esophageal cancer. In the past decades, significant improvements in the planning and delivery of radiation techniques have led to better dose conformity to the target volume and improved normal tissue sparing. Areas covered: This review focuses on the advances in radiotherapy techniques and summarizes the availably dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, proton therapy, and four-dimensional radiotherapy for esophageal cancer, and discusses the challenges and future development of proton therapy. Expert commentary: Although three-dimensional conformal radiotherapy is the standard radiotherapy technique in esophageal cancer, the retrospectively comparative studies strongly suggest that the dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can translate into improved clinical outcomes, despite the lack of prospective randomized evidence. As a novel form of conventional IMRT technique, volumetric modulated arc therapy can produce equivalent or superior dosimetric quality with significantly higher treatment efficiency in esophageal cancer. Compared with photon therapy, proton therapy has the potential to achieve further clinical improvement due to their physical properties; however, prospective clinical data, long-term results, and cost-effectiveness are needed.

Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hattangadi, Jona A.; Rombi, Barbara; Provincial Agency for Proton Therapy, Trento

2012-07-01

Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, andmore » laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.« less

Electrolysis-induced protonation of VO2 thin film transistor for the metal-insulator phase modulation

NASA Astrophysics Data System (ADS)

Katase, Takayoshi; Endo, Kenji; Ohta, Hiromichi

2016-02-01

Compared to state-of-the-art modulation techniques, protonation is the most ideal to control the electrical and optical properties of transition metal oxides (TMOs) due to its intrinsic non-volatile operation. However, the protonation of TMOs is not typically utilized for solid-state devices because of imperative high-temperature annealing treatment in hydrogen source. Although one solution for room temperature (RT) protonation of TMOs is liquid-phase electrochemistry, it is unsuited for practical purposes due to liquid-leakage problem. Herein we demonstrate solid-state RT-protonation of vanadium dioxide (VO2), which is a well-known thermochromic TMO. We fabricated the three terminal thin-film-transistor structure on an insulating VO2 film using a water-infiltrated nanoporous glass, which serves as a solid electrolyte. For gate voltage application, water electrolysis and protonation/deprotonation of VO2 film surface occurred, leading to reversible metal-insulator phase conversion of ~11-nm-thick VO2 layer. The protonation was clearly accompanied by the structural change from an insulating monoclinic to a metallic tetragonal phase. Present results offer a new route for the development of electro-optically active solid-state devices with TMO materials by engineering RT protonation.

Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview

PubMed Central

Weber, Damien C; Ares, Carmen; Lomax, Antony J; Kurtz, John M

2006-01-01

Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered. PMID:16857055

SU-F-T-528: Relationship Between Tumor Size and Plan Quality Using FFF and Non-FFF Modes in Rapidarc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, F

2016-06-15

Purpose: For a give PTV dose, beam-on time is shorter in the FFF than the non-FFF mode because of higher MU/min. Larger tumors usually require more complex intensity modulation, which might affect plan quality and total MU. We investigated the relationship between PTV size and plan quality using FFF and non-FFF modes. Methods: Two different PTV volumes (PTV and PTV+1 cm margin) were drawn in brain, lung and liver. 3-full to 7-partial arc (Rapidarc) of 6 MV, 1400 MU/min were studied. Plan quality was evaluated by: (a) DVH for PTV and normal tissues, (b) total MU and beam-on time, andmore » (c) passing rate for IMRT plan QA. Results: For the same PTV coverage, DVH for normal tissue was the same or slightly lower in the FFF compared with non-FFF. Total MU was 13% higher in FFF than non-FFF in the 3-arc, 7 Gy treatment, but the difference became smaller when arc number increased to 6–7 for 10–24 Gy. Larger PTV did not affect the difference in the total MU. FFF required a short beam-on time and the ratio of FFF and non-FFF was 0.34 to 0.88 for 7- and 3-arc, respectively. For larger PTV, the ratio increased to 0.45–0.90. Ratio of total MU for large PTV was 3–8% lower in the non-FFF plans. Although the small difference in MU, beam-on time was 1.1 to-1.6 times longer in the 3- and 7-arc non-FFF plans. Plan verification showed the similar gamma index passing rate. Conclusion: While total MU was similar with FFF and non-FFF modes, the beam-on time was shorter in the FFF treatment. The advantage of FFF was greater in treatments with high dose per fraction using more arc numbers. For dose less than 10 Gy, using FFF and non-FFF modes, tumor size did not affect the relationship of total MU, beam-on time.« less

SU-E-T-605: RapidArc Combined with DIBH Technique for Thoracic Esophageal Carcinoma: The Potential Value of Target Immobilization and Reduced Lung Density in Dose Escalation.

PubMed

Yin, Y; Liu, T; Zhai, D

2012-06-01

To compare the dosimetric benefits of Rapidarc (RA) combined with deep inspiration breath-hold (DIBH) with those of other standard techniques, including free breathing (FB) during fixed-field intensity modulated radiation therapy (IMRT) and dual arc RA, in the treatment of patients with thoracic esophageal carcinoma (EC). Ten patients with EC underwent computed tomography (CT) scans under 2 respiration conditions: free-breathing (FB) and DIBH. These scans were used to generate 3-dimensional conformal treatment plans. For breath-hold scans, the patients were brought to reproducible respiration levels using active breathing control (ABC) maneuvers. Planning target volumes (PTVs) for FB plans included a 0.5 cm margin for setup plus a 1 cm margin equal to the extent of tumor motion for respiration. PTVs for DIBH plans included a 0.5 cm margin for setup error and a 0.5 cm margin for residual uncertainty in tumor position. Using a dose level of 60 Gy to the PTV, three treatment plans were generated: IMRT-FB, RA-FB and RA-ABC, and the target and normal tissue volumes were compared, as were the dosimetry parameters. On average, the DIBH technique resulted in increased lung volumes compared with FB techniques. There was no significant differences in gross tumor volume between the two breathing states (p > 0.05); but PTV and heart volume were larger for FB than for DIBH (p < 0.05). The overall CI and HI for the RA-ABC plan was slightly inferior to those of the IMRT- FB and RA-FB plans (p < 0.05 each). With DIBH, the heart was partly out of the beam portals and the average mean heart dose was reduced. Compared with conventional FB, RA combined with DIBH significantly reduced cardiac and pulmonary doses without compromising the target coverage and may reduce treatment toxicity, enabling dose escalation in future prospective studies of patients with EC. © 2012 American Association of Physicists in Medicine.

An efficient inverse radiotherapy planning method for VMAT using quadratic programming optimization.

PubMed

Hoegele, W; Loeschel, R; Merkle, N; Zygmanski, P

2012-01-01

The purpose of this study is to investigate the feasibility of an inverse planning optimization approach for the Volumetric Modulated Arc Therapy (VMAT) based on quadratic programming and the projection method. The performance of this method is evaluated against a reference commercial planning system (eclipse(TM) for rapidarc(TM)) for clinically relevant cases. The inverse problem is posed in terms of a linear combination of basis functions representing arclet dose contributions and their respective linear coefficients as degrees of freedom. MLC motion is decomposed into basic motion patterns in an intuitive manner leading to a system of equations with a relatively small number of equations and unknowns. These equations are solved using quadratic programming under certain limiting physical conditions for the solution, such as the avoidance of negative dose during optimization and Monitor Unit reduction. The modeling by the projection method assures a unique treatment plan with beneficial properties, such as the explicit relation between organ weightings and the final dose distribution. Clinical cases studied include prostate and spine treatments. The optimized plans are evaluated by comparing isodose lines, DVH profiles for target and normal organs, and Monitor Units to those obtained by the clinical treatment planning system eclipse(TM). The resulting dose distributions for a prostate (with rectum and bladder as organs at risk), and for a spine case (with kidneys, liver, lung and heart as organs at risk) are presented. Overall, the results indicate that similar plan qualities for quadratic programming (QP) and rapidarc(TM) could be achieved at significantly more efficient computational and planning effort using QP. Additionally, results for the quasimodo phantom [Bohsung et al., "IMRT treatment planning: A comparative inter-system and inter-centre planning exercise of the estro quasimodo group," Radiother. Oncol. 76(3), 354-361 (2005)] are presented as an example for an extreme concave case. Quadratic programming is an alternative approach for inverse planning which generates clinically satisfying plans in comparison to the clinical system and constitutes an efficient optimization process characterized by uniqueness and reproducibility of the solution.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Alan J.; Vora, Nayana; Suh, Steve

2015-04-01

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed. The first CT set was scanned before the contrast injection and secondary study set was scanned 45 secondsmore » after contrast. The 2 CTs were autoregistered using the same Digital Imaging and Communications in Medicine coordinates. Tomotherapy and RapidArc plans were generated on 1 CT data set and subsequently copied to the second CT set. Dose calculation was performed, and dose difference was analyzed to evaluate the influence of intravenous contrast media. The dose matrix used for comparison included mean, minimum and maximum doses of planning target volume (PTV), PTV dose coverage, and V{sub 45} {sub Gy}, V{sub 30} {sub Gy}, and V{sub 20} {sub Gy} organ doses. Treatment planning on contrasted images generally showed a lower dose to both organs and target than plans on noncontrasted images. The doses for the points of interest placed in the organs and target rarely changed more than 2% in any patient. In conclusion, treatment planning using a contrasted image had insignificant effect on the dose to the organs and targets. In our opinion, only CT with contrast needs to be acquired during the CT simulation for head and neck cancer. Dose calculations performed on contrasted images can potentially underestimate the delivery dose slightly. However, the errors of planning on a contrasted image should not affect the result in clinically significant way.« less

SU-F-T-634: Feasibility Study of Respiratory Gated RapidArc SBRT Using a 6MV FFF Photon Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dou, K; Safaraz, M; Rodgers, J

Purpose: To conduct a feasibility study on retrospective respiratory gating and marker tracking for lung stereotactic body radiotherapy (SBRT) with a gated RapidArc delivery using a 6MV flattened filter free photon mode. Methods: A CIRS dynamic thorax phantom Model 008A with different inserts was used for treatment planning and respiratory gating. 4D CT had a free breathing simulation followed by a respiration gated, ten phased CT using a Philips Brilliance CT with a Varian RPM respiratory gating system. The internal target volume was created from the ten phase gated CT images, followed by exporting to a Varian Eclipse TPS v11more » for treatment planning on the free breath images. Both MIP and AIP were also generated for comparison of planning and target motion tracking. The planned dose was delivered with a 6MV FFF photon beam from a Varian TrueBeam accelerator. Gated target motion was also verified by tracking the implanted makers during delivery using continuous kV imaging in addition to CBCT, kV and MV localization and verification. Results: Gating was studied in three situations of lower, normal, and faster breathing at a respiratory cycle of 5, 15 and 25 breaths per minute, respectively. 4D treatment planning was performed at a normal breathing of 15 breaths per minute. The gated patterns obtained using the TrueBeam IR camera were compared with the planned ones while gating operation was added prior to delivery . Gating was realized only when the measured respiratory patterns matched to the planned ones. The gated target motion was verified within the tolerance by kV and MV imaging. Either free breathing CT or averaged CT images were studied to be good for image guidance to align the target. Conclusion: Gated RapidArc SBRT delivered with a 6MV FFF photon beam is realized using a dynamic lung phantom.« less

Zvezda Launch Coverage

NASA Technical Reports Server (NTRS)

2000-01-01

Footage shows the Proton Rocket (containing the Zvezda module) ready for launch at the Baikonur Cosmodrome in Kazakhstan, Russia. The interior and exterior of Zvezda are seen during construction. Computerized simulations show the solar arrays deploying on Zvezda in space, the maneuvers of the module as it approaches and connects with the International Space Station (ISS), the installation of the Z1 truss on the ISS and its solar arrays deploying, and the installations of the Destiny Laboratory, Remote Manipulator System, and Kibo Experiment Module. Live footage then shows the successful launch of the Proton Rocket.

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses

PubMed Central

Tobo, Ayaka; Tobo, Masayuki; Nakakura, Takashi; Ebara, Masashi; Tomura, Hideaki; Mogi, Chihiro; Im, Dong-Soon; Murata, Naoya; Kuwabara, Atsushi; Ito, Saki; Fukuda, Hayato; Arisawa, Mitsuhiro; Shuto, Satoshi; Nakaya, Michio; Kurose, Hitoshi; Sato, Koichi; Okajima, Fumikazu

2015-01-01

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions. PMID:26070068

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

PubMed

Tobo, Ayaka; Tobo, Masayuki; Nakakura, Takashi; Ebara, Masashi; Tomura, Hideaki; Mogi, Chihiro; Im, Dong-Soon; Murata, Naoya; Kuwabara, Atsushi; Ito, Saki; Fukuda, Hayato; Arisawa, Mitsuhiro; Shuto, Satoshi; Nakaya, Michio; Kurose, Hitoshi; Sato, Koichi; Okajima, Fumikazu

2015-01-01

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions.

TIME DEPENDENCE OF THE PROTON FLUX MEASURED BY PAMELA DURING THE 2006 JULY-2009 DECEMBER SOLAR MINIMUM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adriani, O.; Bongi, M.; Barbarino, G. C.

2013-03-10

The energy spectra of galactic cosmic rays carry fundamental information regarding their origin and propagation. These spectra, when measured near Earth, are significantly affected by the solar magnetic field. A comprehensive description of the cosmic radiation must therefore include the transport and modulation of cosmic rays inside the heliosphere. During the end of the last decade, the Sun underwent a peculiarly long quiet phase well suited to study modulation processes. In this paper we present proton spectra measured from 2006 July to 2009 December by PAMELA. The large collected statistics of protons allowed the time variation to be followed onmore » a nearly monthly basis down to 400 MV. Data are compared with a state-of-the-art three-dimensional model of solar modulation.« less

Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaudhary, Pankaj; Marshall, Thomas I.; Currell, Frederick J.

Purpose: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. Methods and Materials: Human skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, andmore » distal positions of SOBP and the entrance and peak position for the pristine beam. Results: A significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci. Conclusions: The DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions.« less

Sparse-view proton computed tomography using modulated proton beams.

PubMed

Lee, Jiseoc; Kim, Changhwan; Min, Byungjun; Kwak, Jungwon; Park, Seyjoon; Lee, Se Byeong; Park, Sungyong; Cho, Seungryong

2015-02-01

Proton imaging that uses a modulated proton beam and an intensity detector allows a relatively fast image acquisition compared to the imaging approach based on a trajectory tracking detector. In addition, it requires a relatively simple implementation in a conventional proton therapy equipment. The model of geometric straight ray assumed in conventional computed tomography (CT) image reconstruction is however challenged by multiple-Coulomb scattering and energy straggling in the proton imaging. Radiation dose to the patient is another important issue that has to be taken care of for practical applications. In this work, the authors have investigated iterative image reconstructions after a deconvolution of the sparsely view-sampled data to address these issues in proton CT. Proton projection images were acquired using the modulated proton beams and the EBT2 film as an intensity detector. Four electron-density cylinders representing normal soft tissues and bone were used as imaged object and scanned at 40 views that are equally separated over 360°. Digitized film images were converted to water-equivalent thickness by use of an empirically derived conversion curve. For improving the image quality, a deconvolution-based image deblurring with an empirically acquired point spread function was employed. They have implemented iterative image reconstruction algorithms such as adaptive steepest descent-projection onto convex sets (ASD-POCS), superiorization method-projection onto convex sets (SM-POCS), superiorization method-expectation maximization (SM-EM), and expectation maximization-total variation minimization (EM-TV). Performance of the four image reconstruction algorithms was analyzed and compared quantitatively via contrast-to-noise ratio (CNR) and root-mean-square-error (RMSE). Objects of higher electron density have been reconstructed more accurately than those of lower density objects. The bone, for example, has been reconstructed within 1% error. EM-based algorithms produced an increased image noise and RMSE as the iteration reaches about 20, while the POCS-based algorithms showed a monotonic convergence with iterations. The ASD-POCS algorithm outperformed the others in terms of CNR, RMSE, and the accuracy of the reconstructed relative stopping power in the region of lung and soft tissues. The four iterative algorithms, i.e., ASD-POCS, SM-POCS, SM-EM, and EM-TV, have been developed and applied for proton CT image reconstruction. Although it still seems that the images need to be improved for practical applications to the treatment planning, proton CT imaging by use of the modulated beams in sparse-view sampling has demonstrated its feasibility.

A Nested Phosphorus and Proton Coil Array for Brain Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2015-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7 Tesla. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4 cm nominal isotropic resolution in 15 min (2.3 cm actual resolution), while additionally enabling 1 mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer’s and Parkinson’s diseases, as well as mental disorders such as schizophrenia. PMID:26375209

A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy.

PubMed

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2016-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell–Mediated Killing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gameiro, Sofia R.; Malamas, Anthony S.; Bernstein, Michael B.

Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen–specific T cells with proton radiation therapy to exploit the activity of those T cells. Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibilitymore » leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells. Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.« less

Background Rejection of Charged Particles in the Simbol-X Telescope: Preliminary Study of Protons Scattering

NASA Astrophysics Data System (ADS)

Dell'Orto, E.; Barbera, M.; Bulgarelli, A.; Fioretti, V.; Malaguti, G.; Mineo, T.; Pareschi, G.; Rigato, V.; Spiga, D.; Tagliaferri, G.

2009-05-01

X-ray telescopes equipped with focusing optics in high eccentric orbit, as e.g. Newton-XMM and Chandra, showed a degradation of the detector performance and an important increase of the noise due to soft protons with energy between a few tens of keV and a few MeV, that are focused on the detector through the mirror module. It should be noted that the focusing of the protons by Wolter optics was an unexpected phenomenon. In Simbol-X a magnetic diverter will be implemented to deflect protons, in order to reduce the flux of charged particles impinging upon the focal plane. Obviously the design of the diverter should take into consideration the protons distribution at the exit of the mirror module; for this reason a detailed simulation about the interaction of particles with the mirror surface is necessary. Here we will present the scattering protons models currently under consideration, suggesting a preliminary solution for the design of the magnetic diverter. We will also discuss an ad hoc experiment to study this problem.

Proton Radiotherapy for Childhood Ependymoma: Initial Clinical Outcomes and Dose Comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M.; Safai, Sairos; Trofimov, Alexei

2008-07-15

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial andmore » supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.« less

Proton therapy for locally advanced breast cancer: A systematic review of the literature.

PubMed

Kammerer, Emmanuel; Guevelou, Jennifer Le; Chaikh, Abdulhamid; Danhier, Serge; Geffrelot, Julien; Levy, Christelle; Saloux, Eric; Habrand, Jean-Louis; Thariat, Juliette

2018-02-01

Radiation therapy plays a major role in the management of adjuvant breast cancer with nodal involvement, with an iatrogenic increase of cardio-vascular risk. Photon therapy, even with intensity modulation, has the downsides of high mean heart dose and heterogeneous target coverage, particularly in the case of internal mammary irradiation. This systematic review of the literature aims to evaluate proton therapy in locally advanced breast cancer. PubMed was searched for original full-text articles with the following search terms: «Proton Therapy» and «Breast Cancer». On-going trials were collected using the words "Breast Cancer" and "Protons". 13 articles met the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). With proton therapy, volumes receiving 95% of the dose were around 98%, with low volumes receiving 105% of the dose. Proton therapy often decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy than with photon therapy. Cutaneous toxicity observed with double scattering is improved with PBS. Proton therapy reduces mean heart dose in breast cancer irradiation, probably reducing late cardio-vascular toxicity. Large clinical studies will likely confirm a clinical benefit of proton therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electron-proton spectrometer: Summary for critical design review

NASA Technical Reports Server (NTRS)

1972-01-01

The electron-proton spectrometer (EPS) is mounted external to the Skylab module complex on the command service module. It is designed to make a 2 pi omni-directional measurement of electrons and protons which result from solar flares or enhancement of the radiation belts. The EPS data will provide accurate radiation dose information so that uncertain Relative biological effectiveness factors are eliminated by measuring the external particle spectra. Astronaut radiation safety, therefore, can be ensured, as the EPS data can be used to correct or qualify radiation dose measurements recorded by other radiation measuring instrumentation within the Skylab module complex. The EPS has the capability of measuring and extremely wide dynamic radiation dose rate range, approaching 10 to the 7th power. Simultaneously the EPS has the capability to process data from extremely high radiation fields such as might be encountered in the wake of an intense solar flare.

Polaron spin echo envelope modulations in an organic semiconducting polymer

DOE PAGES

Mkhitaryan, V. V.; Dobrovitski, V. V.

2017-06-01

Here, we present a theoretical analysis of the electron spin echo envelope modulation (ESEEM) spectra of polarons in semiconducting π -conjugated polymers. We show that the contact hyperfine coupling and the dipolar interaction between the polaron and the proton spins give rise to different features in the ESEEM spectra. Our theory enables direct selective probe of different groups of nuclear spins, which affect the polaron spin dynamics. Namely, we demonstrate how the signal from the distant protons (coupled to the polaron spin via dipolar interactions) can be distinguished from the signal coming from the protons residing on the polaron sitemore » (coupled to the polaron spin via contact hyperfine interaction). We propose a method for directly probing the contact hyperfine interaction, that would enable detailed study of the polaron orbital state and its immediate environment. Lastly, we also analyze the decay of the spin echo modulation, and its connection to the polaron transport.« less

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

Present Status and Future Developments in Proton Therapy

NASA Astrophysics Data System (ADS)

Smith, Alfred R.

2009-07-01

Within the past few years, interest in proton therapy has significantly increased. This interest has been generated by a number of factors including: 1) the reporting of positive clinical results using proton beams; 2) approval of reimbursement for delivery of proton therapy; 3) the success of hospital-based proton therapy centers; and 4) the availability of modern, integrated proton therapy technology for hospital-based facilities. In the United States, this increased interest has occurred particularly at the level of smaller academic hospitals, community medical centers, and large private practices; however, interest from large academic centers continues to be strong. Particular interest exists regarding smaller and less-expensive proton therapy systems, especially the so-called "single-room" systems. In this paper, the advantages and disadvantages of 1-room proton therapy systems will be discussed. The emphasis on smaller and cheaper proton therapy facilities has also generated interest in new proton-accelerating technologies such as superconducting cyclotrons and synchrocyclotrons, laser acceleration, and dielectric-wall accelerators. Superconducting magnets are also being developed to decrease the size and weight of isocentric gantries. Another important technical development is spot-beam scanning, which offers the ability to deliver intensity-modulated proton treatments (IMPT). IMPT has the potential to provide dose distributions that are superior to those for photon intensity modulation techniques (IMXT) and to improve clinical outcomes for patients undergoing cancer therapy. At the present time, only two facilities—one in Europe and one in the United States—have the ability to deliver IMPT treatments, however, within the next year or two several additional facilities are expected to achieve this capability.

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

PubMed

Dedes, G; De Angelis, L; Rit, S; Hansen, D; Belka, C; Bashkirov, V; Johnson, R P; Coutrakon, G; Schubert, K E; Schulte, R W; Parodi, K; Landry, G

2017-07-12

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

WE-EF-BRA-06: Feasibility of Spatially Modulated Proton Beams for Small Animal Research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, E; Meyer, J

Purpose: To investigate the feasibility of proton minibeam radiotherapy (pMBRT) for small animal research. The motivation is to explore with protons the extraordinary normal tissue sparing effects to spatially modulated beams as observed on high flux synchrotron beam lines. We hypothesized that we can design a multi-slit collimator for our proton beam line to produce planar-parallel dose profiles with high modulation in the entrance region and homogenous dose coverage in the overlap of the Bragg peaks. Methods: The high dose rate 50 MeV research proton beamline at the University of Washington was modeled using the TOol for PArticle Simulation (TOPAS)more » Monte Carlo package. A brass collimator was implemented to generate proton minibeams. The collimator consists of an array of 2 cm long slits to cover an area of 2×2 cm{sup 2}. The slit widths (0.1–1 mm), center-to-center (ctc) distances (1–3 mm) and collimator thickness (1–7 cm) were varied to evaluate the effect on dose rate, the peak-to-valley dose ratios (PVDR) and the change of penumbra and peak width (FWHM) with depth. Results: The Bragg peak was at a depth of ∼21 mm. The penumbra and FWHM remained relatively constant to a depth of about 10–15 mm. The PVDR ranged from 1.6 to 26 and the dose rate dropped exponentially with collimator thickness. A uniform dose can be achieved at depth with slightly compromised PVDRs and dose rate. Conclusion: The technical realization of pMBRT is feasible. The simulations have shown that it is possible to obtain uniform dose at depth while modulation is maintained on the entrance side. While the simulated beam widths are larger than on synchrotron generated microbeams the dosimetric advantage could avoid having to interlace two microbeams to achieve uniform dose in the target. The next steps are to build a collimator and verify the simulations experimentally.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plautz, Tia E.; Johnson, R. P.; Sadrozinski, H. F.-W.

Purpose: To characterize the modulation transfer function (MTF) of the pre-clinical (phase II) head scanner developed for proton computed tomography (pCT) by the pCT collaboration. To evaluate the spatial resolution achievable by this system. Methods: Our phase II proton CT scanner prototype consists of two silicon telescopes that track individual protons upstream and downstream from a phantom, and a 5-stage scintillation detector that measures a combination of the residual energy and range of the proton. Residual energy is converted to water equivalent path length (WEPL) of the protons in the scanned object. The set of WEPL values and associated pathsmore » of protons passing through the object over a 360° angular scan is processed by an iterative parallelizable reconstruction algorithm that runs on GP-GPU hardware. A custom edge phantom composed of water-equivalent polymer and tissue-equivalent material inserts was constructed. The phantom was first simulated in Geant4 and then built to perform experimental beam tests with 200 MeV protons at the Northwestern Medicine Chicago Proton Center. The oversampling method was used to construct radial and azimuthal edge spread functions and modulation transfer functions. The spatial resolution was defined by the 10% point of the modulation transfer function in units of lp/cm. Results: The spatial resolution of the image was found to be strongly correlated with the radial position of the insert but independent of the relative stopping power of the insert. The spatial resolution varies between roughly 4 and 6 lp/cm in both the the radial and azimuthal directions depending on the radial displacement of the edge. Conclusion: The amount of image degradation due to our detector system is small compared with the effects of multiple Coulomb scattering, pixelation of the image and the reconstruction algorithm. Improvements in reconstruction will be made in order to achieve the theoretical limits of spatial resolution.« less

SU-F-T-146: Comparing Monte Carlo Simulations with Commissioning Beam Data for Mevion S250 Proton Therapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prusator, M; Jin, H; Ahmad, S

2016-06-15

Purpose: To evaluate the Monte Carlo simulated beam data with the measured commissioning data for the Mevion S250 proton therapy system. Method: The Mevion S250 proton therapy system utilizes a passive double scattering technique with a unique gantry mounted superconducting accelerator and offers effective proton therapy in a compact design concept. The field shaping system (FSS) includes first scattering foil, range modulator wheel (RMW), second scattering foil and post absorber and offers two field sizes and a total of 24 treatment options from proton range of 5 cm to 32 cm. The treatment nozzle was modeled in detail using TOPASmore » (TOolkit for PArticle Simulation) Monte Carlo code. The timing feathers of the moving modulator wheels were also implemented to generate the Spread Out Bragg Peak (SOBP). The simulation results including pristine Bragg Peak, SOBP and dose profiles were compared with the data measured during beam commissioning. Results: The comparison between the measured data and the simulation data show excellent agreement. For pristine proton Bragg Peaks, the simulated proton range (depth of distal 90%) values agreed well with the measured range values within 1 mm accuracy. The differences of the distal falloffs (depth from distal 80% to 20%) were also found to be less than 1 mm between the simulations and measurements. For the SOBP, the widths of modulation (depth of proximal 95% to distal 90%) were also found to agree with the measurement within 1 mm. The flatness of the simulated and measured lateral profiles was found to be 0.6 % and 1.1 %, respectively. Conclusion: The agreement between simulations and measurements demonstrate that TOPAS could be used as a viable platform to proton therapy applications. The matched simulation results offer a great tool and open opportunity for variety of applications.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Underwood, Tracy, E-mail: tunderwood@mgh.harvard.edu; Department of Medical Physics and Bioengineering, University College London, London; Giantsoudi, Drosoula

Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions weremore » simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.« less

NEW EVIDENCE FOR CHARGE-SIGN-DEPENDENT MODULATION DURING THE SOLAR MINIMUM OF 2006 TO 2009

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Felice, V.; Munini, R.; Vos, E. E.

The PAMELA space experiment, in orbit since 2006, has measured cosmic rays (CRs) through the most recent period of minimum solar activity with the magnetic field polarity as A  < 0. During this entire time, galactic electrons and protons have been detected down to 70 MV and 400 MV, respectively, and their differential variation in intensity with time has been monitored with unprecedented accuracy. These observations are used to show how differently electrons and protons responded to the quiet modulation conditions that prevailed from 2006 to 2009. It is well known that particle drifts, as one of four major mechanisms for the solarmore » modulation of CRs, cause charge-sign-dependent solar modulation. Periods of minimum solar activity provide optimal conditions in which to study these drift effects. The observed behavior is compared to the solutions of a three-dimensional model for CRs in the heliosphere, including drifts. The numerical results confirm that the difference in the evolution of electron and proton spectra during the last prolonged solar minimum is attributed to a large extent to particle drifts. We therefore present new evidence of charge-sign-dependent solar modulation, with a perspective on its peculiarities for the observed period from 2006 to 2009.« less

Ipsilateral kidney sparing in treatment of pancreatic malignancies using volumetric-modulated arc therapy avoidance sectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Raymond W., E-mail: rwc3b@alumni.virginia.edu; Podgorsak, Matthew B.

Recent research has shown treating pancreatic cancer with volumetric-modulated arc therapy (VMAT) to be superior to either intensity-modulated radiation therapy or 3-dimensional conformal radiotherapy (3D-CRT), with respect to reducing normal tissue toxicity, monitor units, and treatment time. Furthermore, using avoidance sectors with RapidArc planning can further reduce normal tissue dose while maintaining target conformity. This study looks at the methods in reducing dose to the ipsilateral kidney, in pancreatic head cases, while observing dose received by other critical organs using avoidance sectors. Overall, 10 patients were retrospectively analyzed. Each patient had preoperative/unresectable pancreatic tumor and were selected based on themore » location of the right kidney being situated within the traditional 3D-CRT treatment field. The target planning target volume (286.97 ± 85.17 cm{sup 3}) was prescribed to 50.4 Gy using avoidance sectors of 30°, 40°, and 50° and then compared with VMAT as well as 3D-CRT. Analysis of the data shows that the mean dose to the right kidney was reduced by 11.6%, 15.5%, and 21.9% for avoidance angles of 30°, 40°, and 50°, respectively, over VMAT. The mean dose to the total kidney also decreased by 6.5%, 8.5%, and 11.0% for the same increasing angles. Spinal cord maximum dose, however, increased as a function of angle by 3.7%, 4.8%, and 6.1% compared with VMAT. Employing avoidance sector angles as a complement to VMAT planning can significantly reduce high dose to the ipsilateral kidney while not greatly overdosing other critical organs.« less

Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery.

PubMed

Engelsman, M; Lu, H M; Herrup, D; Bussiere, M; Kooy, H M

2009-06-01

Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output.

SU-F-P-39: End-To-End Validation of a 6 MV High Dose Rate Photon Beam, Configured for Eclipse AAA Algorithm Using Golden Beam Data, for SBRT Treatments Using RapidArc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferreyra, M; Salinas Aranda, F; Dodat, D

Purpose: To use end-to-end testing to validate a 6 MV high dose rate photon beam, configured for Eclipse AAA algorithm using Golden Beam Data (GBD), for SBRT treatments using RapidArc. Methods: Beam data was configured for Varian Eclipse AAA algorithm using the GBD provided by the vendor. Transverse and diagonals dose profiles, PDDs and output factors down to a field size of 2×2 cm2 were measured on a Varian Trilogy Linac and compared with GBD library using 2% 2mm 1D gamma analysis. The MLC transmission factor and dosimetric leaf gap were determined to characterize the MLC in Eclipse. Mechanical andmore » dosimetric tests were performed combining different gantry rotation speeds, dose rates and leaf speeds to evaluate the delivery system performance according to VMAT accuracy requirements. An end-to-end test was implemented planning several SBRT RapidArc treatments on a CIRS 002LFC IMRT Thorax Phantom. The CT scanner calibration curve was acquired and loaded in Eclipse. PTW 31013 ionization chamber was used with Keithley 35617EBS electrometer for absolute point dose measurements in water and lung equivalent inserts. TPS calculated planar dose distributions were compared to those measured using EPID and MapCheck, as an independent verification method. Results were evaluated with gamma criteria of 2% dose difference and 2mm DTA for 95% of points. Results: GBD set vs. measured data passed 2% 2mm 1D gamma analysis even for small fields. Machine performance tests show results are independent of machine delivery configuration, as expected. Absolute point dosimetry comparison resulted within 4% for the worst case scenario in lung. Over 97% of the points evaluated in dose distributions passed gamma index analysis. Conclusion: Eclipse AAA algorithm configuration of the 6 MV high dose rate photon beam using GBD proved efficient. End-to-end test dose calculation results indicate it can be used clinically for SBRT using RapidArc.« less

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Studenski, M; Abramowitz, M; Dogan, N

Purpose: Quantify the dosimetric cost for a margin around the MRI-defined high risk GTV for simultaneous integrated intra-prostatic boosts (SIIB) treated with RapidArc. Methods: For external beam radiotherapy of the prostate, a 3-7 mm PTV margin is typically used to account for setup and intra-fraction uncertainties after adjusting for inter-fraction motion. On the other hand, our current paradigm is to treat the MRI-defined high risk GTV with no margin. In this work, 11 patients treated SIIB (7 post-prostatectomy, 4 intact prostate) with RapidArc were re-planned with 1-5 mm margins around the GTV to quantify dosimetric effects. Two 358 degree, 10more » MV RapidArcs were used to deliver 68 Gy (76.5 Gy boost) to the post-prostatectomy patients and 80 Gy (86 Gy boost) to the intact prostates. Paired, two tail t-tests were used to determine if there were any significant differences (p<0.05) in the total MUs and dosimetric parameters used to evaluate rectum, bladder, and PTV dose with and without margin. Results: The average GTV volume without margin was 8.1cc (2.8% of the PTV volume) while the average GTV volume with a 5 mm margin was 20.1cc (9.0% of the PTV volume). GTV volumes ranged from 0.2% of the PTV volume up to 33.0%. Despite these changes in volume, the only statistical difference was found for the rectal V65 Gy with a 5 mm margin (18.6% vs. 19.4%; p-value = 0.026) when all patients were considered as a single group. No difference was found when analyzed as two groups. The rectum V40Gy, bladder V40Gy and V65Gy, PTV Dmax and D95% or the total MUs did not show any significant difference for any margin. Conclusion: A 4 mm margin on the high risk GTV is possible with no statistically significant change in dosimetry or total MUs. Further work will assess the appropriate margin required for intra-prostatic boosts.« less

Fast modulations of pulsating proton aurora related to subpacket structures of Pc1 geomagnetic pulsations at subauroral latitudes

DOE PAGES

Ozaki, M.; Shiokawa, K.; Miyoshi, Y.; ...

2016-08-16

To understand the role of electromagnetic ion cyclotron (EMIC) waves in determining the temporal features of pulsating proton aurora (PPA) via wave-particle interactions at subauroral latitudes, high-time-resolution (1/8 s) images of proton-induced N 2>+ emissions were recorded using a new electron multiplying charge-coupled device camera, along with related Pc1 pulsations on the ground. The observed Pc1 pulsations consisted of successive rising-tone elements with a spacing for each element of 100 s and subpacket structures, which manifest as amplitude modulations with a period of a few tens of seconds. In accordance with the temporal features of the Pc1 pulsations, the auroralmore » intensity showed a similar repetition period of 100 s and an unpredicted fast modulation of a few tens of seconds. Furthermore, these results indicate that PPA is generated by pitch angle scattering, nonlinearly interacting with Pc1/EMIC waves at the magnetic equator.« less

Fast modulations of pulsating proton aurora related to subpacket structures of Pc1 geomagnetic pulsations at subauroral latitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozaki, M.; Shiokawa, K.; Miyoshi, Y.

To understand the role of electromagnetic ion cyclotron (EMIC) waves in determining the temporal features of pulsating proton aurora (PPA) via wave-particle interactions at subauroral latitudes, high-time-resolution (1/8 s) images of proton-induced N 2>+ emissions were recorded using a new electron multiplying charge-coupled device camera, along with related Pc1 pulsations on the ground. The observed Pc1 pulsations consisted of successive rising-tone elements with a spacing for each element of 100 s and subpacket structures, which manifest as amplitude modulations with a period of a few tens of seconds. In accordance with the temporal features of the Pc1 pulsations, the auroralmore » intensity showed a similar repetition period of 100 s and an unpredicted fast modulation of a few tens of seconds. Furthermore, these results indicate that PPA is generated by pitch angle scattering, nonlinearly interacting with Pc1/EMIC waves at the magnetic equator.« less

The evolution of Saturn's radiation belts modulated by changes in radial diffusion

NASA Astrophysics Data System (ADS)

Kollmann, P.; Roussos, E.; Kotova, A.; Paranicas, C.; Krupp, N.

2017-12-01

Globally magnetized planets, such as the Earth1 and Saturn2, are surrounded by radiation belts of protons and electrons with kinetic energies well into the million electronvolt range. The Earth's proton belt is supplied locally from galactic cosmic rays interacting with the atmosphere3, as well as from slow inward radial transport4. Its intensity shows a relationship with the solar cycle4,5 and abrupt dropouts due to geomagnetic storms6,7. Saturn's proton belts are simpler than the Earth's because cosmic rays are the principal source of energetic protons8 with virtually no contribution from inward transport, and these belts can therefore act as a prototype to understand more complex radiation belts. However, the time dependence of Saturn's proton belts had not been observed over sufficiently long timescales to test the driving mechanisms unambiguously. Here we analyse the evolution of Saturn's proton belts over a solar cycle using in-situ measurements from the Cassini Saturn orbiter and a numerical model. We find that the intensity in Saturn's proton radiation belts usually rises over time, interrupted by periods that last over a year for which the intensity is gradually dropping. These observations are inconsistent with predictions based on a modulation in the cosmic-ray source, as could be expected4,9 based on the evolution of the Earth's proton belts. We demonstrate that Saturn's intensity dropouts result instead from losses due to abrupt changes in magnetospheric radial diffusion.

The Potential Benefit of Radiotherapy with Protons in Head and Neck Cancer with Respect to Normal Tissue Sparing: A Systematic Review of Literature

PubMed Central

Bijl, Hendrik P.; Schilstra, Cornelis; Pijls-Johannesma, Madelon; Langendijk, Johannes A.

2011-01-01

Purpose. Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation-induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies. Materials and Methods. A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques. Results. Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancer cases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studies compared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction. Conclusion. The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials. PMID:21349950

Drift and observations in cosmic-ray modulation, 1

NASA Technical Reports Server (NTRS)

Potgieter, M. S.

1985-01-01

It is illustrated that a relative simple drift model can, in contrast with no drift models, simultaneously fit proton and electron spectra observed in 1965-66 and 1977, using a single set of modulation parameters except for a change in the IMF polarity. This result is interpreted together with the observation of Evenson and Meyer that electrons are recovering more rapidly than protons after 1980, in contrast with what Burger and Swanenburg observed in 1968-72, as a charge sign dependent effect due to the occurrence of drift in cosmic ray modulation. The same set of parameters produces a shift in the phase and amplitude of the diurnal anisotropy vector, consistent with observations in 1969-71 and 1980-81.

Proton therapy in the clinic.

PubMed

DeLaney, Thomas F

2011-01-01

The clinical advantage for proton radiotherapy over photon approaches is the marked reduction in integral dose to the patient, due to the absence of exit dose beyond the proton Bragg peak. The integral dose with protons is approximately 60% lower than that with any external beam photon technique. Pediatric patients, because of their developing normal tissues and anticipated length of remaining life, are likely to have the maximum clinical gain with the use of protons. Proton therapy may also allow treatment of some adult tumors to much more effective doses, because of normal tissue sparing distal to the tumor. Currently, the most commonly available proton treatment technology uses 3D conformal approaches based on (a) distal range modulation, (b) passive scattering of the proton beam in its x- and y-axes, and (c) lateral beam-shaping. It is anticipated that magnetic pencil beam scanning will become the dominant mode of proton delivery in the future, which will lower neutron scatter associated with passively scattered beam lines, reduce the need for expensive beam-shaping devices, and allow intensity-modulated proton radiotherapy. Proton treatment plans are more sensitive to variations in tumor size and normal tissue changes over the course of treatment than photon plans, and it is expected that adaptive radiation therapy will be increasingly important for proton therapy as well. While impressive treatment results have been reported with protons, their cost is higher than for photon IMRT. Hence, protons should ideally be employed for anatomic sites and tumors not well treated with photons. While protons appear cost-effective for pediatric tumors, their cost-effectiveness for treatment of some adult tumors, such as prostate cancer, is uncertain. Comparative studies have been proposed or are in progress to more rigorously assess their value for a variety of sites. The utility of proton therapy will be enhanced by technological developments that reduce its cost. Combinations of 3D protons with IMRT photons may offer improved treatment plans at lower cost than pure proton plans. Hypofractionation with proton therapy appears to be safe and cost-effective for many tumor sites, such as for selected liver, lung and pancreas cancers, and may yield significant reduction in the cost of a therapy course. Together, these offer practical strategies for expanding the clinical availability of proton therapy. Copyright © 2011 S. Karger AG, Basel.

WE-D-BRB-00: Basics of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

PubMed

Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

2018-04-25

The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

Linac based SBRT for prostate cancer in 5 fractions with VMAT and flattening filter free beams: preliminary report of a phase II study.

PubMed

Alongi, Filippo; Cozzi, Luca; Arcangeli, Stefano; Iftode, Cristina; Comito, Tiziana; Villa, Elisa; Lobefalo, Francesca; Navarria, Pierina; Reggiori, Giacomo; Mancosu, Pietro; Clerici, Elena; Fogliata, Antonella; Tomatis, Stefano; Taverna, Gianluigi; Graziotti, Pierpaolo; Scorsetti, Marta

2013-07-08

To evaluate the feasibility and early side effects of a short course hypo-fractionated SBRT programme with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams. A prospective phase I-II study, started on February 2012. Inclusion criteria were: age ≤ 80 years, WHO-PS ≤ 2, PSA ≤ 20 ng/ml, histologically proven prostate adenocarcinoma, T1-T2 stage, no distant metastases, no previous surgery other than TURP, no malignant tumours in the previous 5 years, IPSS 0-7. The schedule was 35 Gy in 5 alternative days. SBRT was delivered with RapidArc VMAT, with 10MV FFF photons. Toxicity assessment was performed according to CTCAE v4.0 scale. EPIC questionnaires assessed Quality-of-Life. Neo-adjuvant/concomitant hormonal-therapy was prescribed according to risk classification. SpaceOAR™ gel was optionally implanted to increase the separation space between the prostate and the rectal wall. Median follow-up was 11 months (range: 5-16); 40 patients were recruited in the protocol and treated. According to NCCN criteria, 26/40 patients were low-risk and 14/40 were intermediate risk. Median age was 70 years (56-80), median initial PSA was 6.25 ng/ml (0.50-13.43 ng/ml). Median Gleason score was 6 (6-7). All patients completed the treatment as programmed (median 11.8 days (9-22). Acute Toxicities were as follow: Rectum G0: 30/40 cases (75%); G1: 6/40 (15%); G2: 4/40 (10%). Genito-urinary: G0: 16/40 (40%); G1: 8/40 (20%); G2: 16/34 (40%). In two G2 urinary retention cases, intermittent catheter was needed. No acute G3 or greater toxicity was found. Median treatment time was 126 sec (120-136). SpaceOAR™ was implanted in 8 patients. PSA reduction from the pre-treatment value of the marker was documented in all patients. Early findings suggest that SBRT with RapidArc and FFF beams for prostate cancer in 5 fractions is feasible and tolerated in acute setting. Longer follow-up is needed for assessment of late toxicity and outcome.

Measurement of stray neutron doses inside the treatment room from a proton pencil beam scanning system.

PubMed

Mojżeszek, N; Farah, J; Kłodowska, M; Ploc, O; Stolarczyk, L; Waligórski, M P R; Olko, P

2017-02-01

To measure the environmental doses from stray neutrons in the vicinity of a solid slab phantom as a function of beam energy, field size and modulation width, using the proton pencil beam scanning (PBS) technique. Measurements were carried out using two extended range WENDI-II rem-counters and three tissue equivalent proportional counters. Detectors were suitably placed at different distances around the RW3 slab phantom. Beam irradiation parameters were varied to cover the clinical ranges of proton beam energies (100-220MeV), field sizes ((2×2)-(20×20)cm 2 ) and modulation widths (0-15cm). For pristine proton peak irradiations, large variations of neutron H ∗ (10)/D were observed with changes in beam energy and field size, while these were less dependent on modulation widths. H ∗ (10)/D for pristine proton pencil beams varied between 0.04μSvGy -1 at beam energy 100MeV and a (2×2)cm 2 field at 2.25m distance and 90° angle with respect to the beam axis, and 72.3μSvGy -1 at beam energy 200MeV and a (20×20) cm 2 field at 1m distance along the beam axis. The obtained results will be useful in benchmarking Monte Carlo calculations of proton radiotherapy in PBS mode and in estimating the exposure to stray radiation of the patient. Such estimates may be facilitated by the obtained best-fitted simple analytical formulae relating the stray neutron doses at points of interest with beam irradiation parameters. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dosimetric advantages of IMPT over IMRT for laser-accelerated proton beams

NASA Astrophysics Data System (ADS)

Luo, W.; Li, J.; Fourkal, E.; Fan, J.; Xu, X.; Chen, Z.; Jin, L.; Price, R.; Ma, C.-M.

2008-12-01

As a clinical application of an exciting scientific breakthrough, a compact and cost-efficient proton therapy unit using high-power laser acceleration is being developed at Fox Chase Cancer Center. The significance of this application depends on whether or not it can yield dosimetric superiority over intensity-modulated radiation therapy (IMRT). The goal of this study is to show how laser-accelerated proton beams with broad energy spreads can be optimally used for proton therapy including intensity-modulated proton therapy (IMPT) and achieve dosimetric superiority over IMRT for prostate cancer. Desired energies and spreads with a varying δE/E were selected with the particle selection device and used to generate spread-out Bragg peaks (SOBPs). Proton plans were generated on an in-house Monte Carlo-based inverse-planning system. Fifteen prostate IMRT plans previously used for patient treatment have been included for comparison. Identical dose prescriptions, beam arrangement and consistent dose constrains were used for IMRT and IMPT plans to show the dosimetric differences that were caused only by the different physical characteristics of proton and photon beams. Different optimization constrains and beam arrangements were also used to find optimal IMPT. The results show that conventional proton therapy (CPT) plans without intensity modulation were not superior to IMRT, but IMPT can generate better proton plans if appropriate beam setup and optimization are used. Compared to IMRT, IMPT can reduce the target dose heterogeneity ((D5-D95)/D95) by up to 56%. The volume receiving 65 Gy and higher (V65) for the bladder and the rectum can be reduced by up to 45% and 88%, respectively, while the volume receiving 40 Gy and higher (V40) for the bladder and the rectum can be reduced by up to 49% and 68%, respectively. IMPT can also reduce the whole body non-target tissue dose by up to 61% or a factor 2.5. This study has shown that the laser accelerator under development has a potential to generate high-quality proton beams for cancer treatment. Significant improvement in target dose uniformity and normal tissue sparing as well as in reduction of whole body dose can be achieved by IMPT with appropriate optimization and beam setup.

Analytical probabilistic proton dose calculation and range uncertainties

NASA Astrophysics Data System (ADS)

Bangert, M.; Hennig, P.; Oelfke, U.

2014-03-01

We introduce the concept of analytical probabilistic modeling (APM) to calculate the mean and the standard deviation of intensity-modulated proton dose distributions under the influence of range uncertainties in closed form. For APM, range uncertainties are modeled with a multivariate Normal distribution p(z) over the radiological depths z. A pencil beam algorithm that parameterizes the proton depth dose d(z) with a weighted superposition of ten Gaussians is used. Hence, the integrals ∫ dz p(z) d(z) and ∫ dz p(z) d(z)2 required for the calculation of the expected value and standard deviation of the dose remain analytically tractable and can be efficiently evaluated. The means μk, widths δk, and weights ωk of the Gaussian components parameterizing the depth dose curves are found with least squares fits for all available proton ranges. We observe less than 0.3% average deviation of the Gaussian parameterizations from the original proton depth dose curves. Consequently, APM yields high accuracy estimates for the expected value and standard deviation of intensity-modulated proton dose distributions for two dimensional test cases. APM can accommodate arbitrary correlation models and account for the different nature of random and systematic errors in fractionated radiation therapy. Beneficial applications of APM in robust planning are feasible.

An image-guided precision proton radiation platform for preclinical in vivo research

NASA Astrophysics Data System (ADS)

Ford, E.; Emery, R.; Huff, D.; Narayanan, M.; Schwartz, J.; Cao, N.; Meyer, J.; Rengan, R.; Zeng, J.; Sandison, G.; Laramore, G.; Mayr, N.

2017-01-01

There are many unknowns in the radiobiology of proton beams and other particle beams. We describe the development and testing of an image-guided low-energy proton system optimized for radiobiological research applications. A 50 MeV proton beam from an existing cyclotron was modified to produce collimated beams (as small as 2 mm in diameter). Ionization chamber and radiochromic film measurements were performed and benchmarked with Monte Carlo simulations (TOPAS). The proton beam was aligned with a commercially-available CT image-guided x-ray irradiator device (SARRP, Xstrahl Inc.). To examine the alternative possibility of adapting a clinical proton therapy system, we performed Monte Carlo simulations of a range-shifted 100 MeV clinical beam. The proton beam exhibits a pristine Bragg Peak at a depth of 21 mm in water with a dose rate of 8.4 Gy min-1 (3 mm depth). The energy of the incident beam can be modulated to lower energies while preserving the Bragg peak. The LET was: 2.0 keV µm-1 (water surface), 16 keV µm-1 (Bragg peak), 27 keV µm-1 (10% peak dose). Alignment of the proton beam with the SARRP system isocenter was measured at 0.24 mm agreement. The width of the beam changes very little with depth. Monte Carlo-based calculations of dose using the CT image data set as input demonstrate in vivo use. Monte Carlo simulations of the modulated 100 MeV clinical proton beam show a significantly reduced Bragg peak. We demonstrate the feasibility of a proton beam integrated with a commercial x-ray image-guidance system for preclinical in vivo studies. To our knowledge this is the first description of an experimental image-guided proton beam for preclinical radiobiology research. It will enable in vivo investigations of radiobiological effects in proton beams.

Combining Fourier phase encoding and broadband inversion toward J-edited spectra

NASA Astrophysics Data System (ADS)

Lin, Yulan; Guan, Quanshuai; Su, Jianwei; Chen, Zhong

2018-06-01

Nuclear magnetic resonance (NMR) spectra are often utilized for gathering accurate information relevant to molecular structures and composition assignments. In this study, we develop a homonuclear encoding approach based on imparting a discrete phase modulation of the targeted cross peaks, and combine it with a pure shift experiments (PSYCHE) based J-modulated scheme, providing simple 2D J-edited spectra for accurate measurement of scalar coupling networks. Chemical shifts and J coupling constants of protons coupled to the specific protons are demonstrated along the F2 and F1 dimensions, respectively. Polychromatic pulses by Fourier phase encoding were performed to simultaneously detect several coupling networks. Proton-proton scalar couplings are chosen by a polychromatic pulse and a PSYCHE element. Axis peaks and unwanted couplings are complete eradicated by incorporating a selective COSY block as a preparation period. The theoretical principles and the signal processing procedure are laid out, and experimental observations are rationalized on the basis of theoretical analyses.

Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery

PubMed Central

Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M.

2009-01-01

Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output. PMID:19610306

Electro-optic-waveguide frequency translator in LiNbO(3) fabricated by proton exchange.

PubMed

Wong, K K; De La Rue, R M; Wright, S

1982-11-01

An optical waveguide phase modulator has been fabricated on X-cut LiNbO(3) by using proton exchange in benzoic acid. The phase modulator was operated as a serrodyne optical-frequency translator with shifted-signal to imagesignal discrimination of 52 dB for a 4-MHz frequency shift. The amplitude of the sawtooth driving signal was 10 V peak to peak. Application of a de bias voltage of either polarity was found to cause a substantial reduction in transmitted-light intensity.

New Strategies in Radiation Therapy: Exploiting the Full Potential of Protons

PubMed Central

Mohan, Radhe; Mahajan, Anita; Minsky, Bruce D.

2013-01-01

Protons provide significant dosimetric advantages compared with photons due to their unique depth-dose distribution characteristics. However, they are more sensitive to the effects of intra- and inter-treatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biological effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biological properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. PMID:24077353

New strategies in radiation therapy: exploiting the full potential of protons.

PubMed

Mohan, Radhe; Mahajan, Anita; Minsky, Bruce D

2013-12-01

Protons provide significant dosimetric advantages compared with photons because of their unique depth-dose distribution characteristics. However, they are more sensitive to the effects of intra- and intertreatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biologic effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biologic properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. ©2013 AACR.

Letter to the Editor on 'Single-Arc IMRT?'.

PubMed

Otto, Karl

2009-04-21

In the note 'Single Arc IMRT?' (Bortfeld and Webb 2009 Phys. Med. Biol. 54 N9-20), Bortfeld and Webb present a theoretical investigation of static gantry IMRT (S-IMRT), single-arc IMRT and tomotherapy. Based on their assumptions they conclude that single-arc IMRT is inherently limited in treating complex cases without compromising delivery efficiency. Here we present an expansion of their work based on the capabilities of the Varian RapidArc single-arc IMRT system. Using the same theoretical framework we derive clinically deliverable single-arc IMRT plans based on these specific capabilities. In particular, we consider the range of leaf motion, the ability to rapidly and continuously vary the dose rate and the choice of collimator angle used for delivery. In contrast to the results of Bortfeld and Webb, our results show that single-arc IMRT plans can be generated that closely match the theoretical optimum. The disparity in the results of each investigation emphasizes that the capabilities of the delivery system, along with the ability of the optimization algorithm to exploit those capabilities, are of particular importance in single-arc IMRT. We conclude that, given the capabilities available with the RapidArc system, single-arc IMRT can produce complex treatment plans that are delivered efficiently (in approximately 2 min).

Flexible Proton-Gated Oxide Synaptic Transistors on Si Membrane.

PubMed

Zhu, Li Qiang; Wan, Chang Jin; Gao, Ping Qi; Liu, Yang Hui; Xiao, Hui; Ye, Ji Chun; Wan, Qing

2016-08-24

Ion-conducting materials have received considerable attention for their applications in fuel cells, electrochemical devices, and sensors. Here, flexible indium zinc oxide (InZnO) synaptic transistors with multiple presynaptic inputs gated by proton-conducting phosphorosilicate glass-based electrolyte films are fabricated on ultrathin Si membranes. Transient characteristics of the proton gated InZnO synaptic transistors are investigated, indicating stable proton-gating behaviors. Short-term synaptic plasticities are mimicked on the proposed proton-gated synaptic transistors. Furthermore, synaptic integration regulations are mimicked on the proposed synaptic transistor networks. Spiking logic modulations are realized based on the transition between superlinear and sublinear synaptic integration. The multigates coupled flexible proton-gated oxide synaptic transistors may be interesting for neuroinspired platforms with sophisticated spatiotemporal information processing.

Measurements of neutron dose equivalent for a proton therapy center using uniform scanning proton beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng Yuanshui; Liu Yaxi; Zeidan, Omar

Purpose: Neutron exposure is of concern in proton therapy, and varies with beam delivery technique, nozzle design, and treatment conditions. Uniform scanning is an emerging treatment technique in proton therapy, but neutron exposure for this technique has not been fully studied. The purpose of this study is to investigate the neutron dose equivalent per therapeutic dose, H/D, under various treatment conditions for uniform scanning beams employed at our proton therapy center. Methods: Using a wide energy neutron dose equivalent detector (SWENDI-II, ThermoScientific, MA), the authors measured H/D at 50 cm lateral to the isocenter as a function of proton range,more » modulation width, beam scanning area, collimated field size, and snout position. They also studied the influence of other factors on neutron dose equivalent, such as aperture material, the presence of a compensator, and measurement locations. They measured H/D for various treatment sites using patient-specific treatment parameters. Finally, they compared H/D values for various beam delivery techniques at various facilities under similar conditions. Results: H/D increased rapidly with proton range and modulation width, varying from about 0.2 mSv/Gy for a 5 cm range and 2 cm modulation width beam to 2.7 mSv/Gy for a 30 cm range and 30 cm modulation width beam when 18 Multiplication-Sign 18 cm{sup 2} uniform scanning beams were used. H/D increased linearly with the beam scanning area, and decreased slowly with aperture size and snout retraction. The presence of a compensator reduced the H/D slightly compared with that without a compensator present. Aperture material and compensator material also have an influence on neutron dose equivalent, but the influence is relatively small. H/D varied from about 0.5 mSv/Gy for a brain tumor treatment to about 3.5 mSv/Gy for a pelvic case. Conclusions: This study presents H/D as a function of various treatment parameters for uniform scanning proton beams. For similar treatment conditions, the H/D value per uncollimated beam size for uniform scanning beams was slightly lower than that from a passive scattering beam and higher than that from a pencil beam scanning beam, within a factor of 2. Minimizing beam scanning area could effectively reduce neutron dose equivalent for uniform scanning beams, down to the level close to pencil beam scanning.« less

Measurements of lateral penumbra for uniform scanning proton beams under various beam delivery conditions and comparison to the XiO treatment planning system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rana, Suresh; Zeidan, Omar; Ramirez, Eric

2013-09-15

Purpose: The main purposes of this study were to (1) investigate the dependency of lateral penumbra (80%–20% distance) of uniform scanning proton beams on various factors such as air gap, proton range, modulation width, compensator thickness, and depth, and (2) compare the lateral penumbra calculated by a treatment planning system (TPS) with measurements.Methods: First, lateral penumbra was measured using solid–water phantom and radiographic films for (a) air gap, ranged from 0 to 35 cm, (b) proton range, ranged from 8 to 30 cm, (c) modulation, ranged from 2 to 10 cm, (d) compensator thickness, ranged from 0 to 20 cm,more » and (e) depth, ranged from 7 to 15 cm. Second, dose calculations were computed in a virtual water phantom using the XiO TPS with pencil beam algorithm for identical beam conditions and geometrical configurations that were used for the measurements. The calculated lateral penumbra was then compared with the measured one for both the horizontal and vertical scanning magnets of our uniform scanning proton beam delivery system.Results: The results in the current study showed that the lateral penumbra of horizontal scanning magnet was larger (up to 1.4 mm for measurement and up to 1.0 mm for TPS) compared to that of vertical scanning magnet. Both the TPS and measurements showed an almost linear increase in lateral penumbra with increasing air gap as it produced the greatest effect on lateral penumbra. Lateral penumbra was dependent on the depth and proton range. Specifically, the width of lateral penumbra was found to be always lower at shallower depth than at deeper depth within the spread out Bragg peak (SOBP) region. The lateral penumbra results were less sensitive to the variation in the thickness of compensator, whereas lateral penumbra was independent of modulation. Overall, the comparison between the results of TPS with that of measurements indicates a good agreement for lateral penumbra, with TPS predicting higher values compared to measurements.Conclusions: Lateral penumbra of uniform scanning proton beams depends on air gap, proton range, compensator thickness, and depth, whereas lateral penumbra is not dependent on modulation. The XiO TPS typically overpredicted lateral penumbra compared to measurements, within 1 mm for most cases, but the difference could be up to 2.5 mm at a deep depth and large air gap.« less

WE-F-16A-03: 3D Printer Application in Proton Therapy: A Novel Method to Deliver Passive-Scattering Proton Beams with a Fixed Range and Modulation for SRS and SRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Witztum, A; Liang, X

2014-06-15

Purpose: To present a novel technique to deliver passive-scattering proton beam with fixed range and modulation using a 3D printed patient-specific bolus for proton stereotactic radiosurgery and radiotherapy. Methods: A CIRS head phantom was used to simulate a patient with a small brain lesion. A custom bolus was created in the Eclipse Treatment Planning System (TPS) to compensate for the different water equivalent depths from the patient surface to the target from multiple beam directions. To simulate arc therapy, a plan was created on the initial CT using three passive-scattering proton beams with a fixed range and modulations irradiating frommore » different angles. The DICOM-RT structure file of the bolus was exported from the TPS and converted to STL format for 3D printing. The phantom was rescanned with the printed custom bolus and head cup to verify the dose distribution comparing to the initial plan. EBT3 films were placed in the sagital plane of the target to verify the delivered dose distribution. The relative stopping power of the printing material(ABSplus-P430) was measured using the Zebra multi-plate ion chamber. Results: The relative stopping power of the 3D printing material, ABSplus-P430 was 1.05 which is almost water equivalent. The dose difference between verification CT and Initial CT is almost negligible. Film measurement also confirmed the accuracy for this new proton delivery technique. Conclusion: Our method using 3D printed range modifiers simplify the treatment delivery of multiple passive-scattering beams in treatment of small lesion in brain. This technique makes delivery of multiple beam more efficient and can be extended to allow arc therapy with proton beams. The ability to create and construct complex patient specific bolus structures provides a new dimension in creating optimized quality treatment plans not only for proton therapy but also for electron and photon therapy.« less

Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Sengbusch, Evan R.

Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

MO-F-CAMPUS-T-04: Utilization of Optical Dosimeter for Modulated Spot-Scanning Particle Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsi, W; Li, Y; Huang, Z

Purpose: To present the utilization of an optical dosimeter for modulated spot-scanning carbon-ion and proton beams during the acceptance test of Siemens IONTRIS system. Method and Materials: An optical dosimeter using phosphor scintillation was developed to map and interactively analyze the shapes and sizes of spots over 190 energies for ProTom modulated-scanning system. The dose response to proton had been characterized with proper pixel calibration at ProTom system. The dose response was further studied at 0.7 cm depths by uniform 8cm in-diameter fields of 424.89 MeV/u (E290) carbon-ions and 215.18MeV (E282) protons at IONTRIS system. The virtual source axial distancesmore » (vSAD) of carbonions and protons of IONTRIS system was investigated by measuring either variations of spot position or field size at five different locations to Isocenter. By measuring lateral profiles of uniform doses with varied thin-thicknesses of chest-board pattern and placing the scintillation plate at near to the distal edge, range variations at different off-axis-distances (rOAD) were examined. Relative accuracy and reproducibility of beam range were measured for three beam ranges with a ramping block at front of scintillation plate. Results: Similar dose response was observed for high energies of carbon ions and protons. Mean vSAD at X and Y axes were 744.1 cm and 807.4cm with deviation of 7.4cm and 7.7cm, respectively. Variation of rOAD was within 0.35 mm over 10cm for both protons and carbon ions. Accuracy of measuring relative distal range using the ramping block was 0.2mm. Measured range over repeated three times for each range were within 0.25mm at same room, and within 1.0mm between four rooms. Conclusions: The optical dosimeter could efficiently measure the virtual source distance. And, to measure small range variation at different off-axial locations, and for the relative beam range between rooms during acceptance test of a modulated spot-scanning particle system.« less

Optimization, Characterization and Commissioning of a Novel Uniform Scanning Proton Beam Delivery System

NASA Astrophysics Data System (ADS)

Mascia, Anthony Edward

Purpose: To develop and characterize the required detectors for uniform scanning optimization and characterization, and to develop the methodology and assess their efficacy for optimizing, characterizing and commissioning a novel proton beam uniform scanning system. Methods and Materials: The Multi Layer Ion Chamber (MLIC), a 1D array of vented parallel plate ion chambers, was developed in-house for measurement of longitudinal profiles. The Matrixx detector (IBA Dosimetry, Germany) and XOmat V film (Kodak, USA) were characterized for measurement of transverse profiles. The architecture of the uniform scanning system was developed and then optimized and characterized for clinical proton radiotherapy. Results: The MLIC detector significantly increased data collection efficiency without sacrificing data quality. The MLIC was capable of integrating an entire scanned and layer stacked proton field with one measurement, producing results with the equivalent spatial sampling of 1.0mm. The Matrixx detector and modified 1D water phantom jig improved data acquisition efficiency and complemented the film measurements. The proximal, central and distal proton field planes were measured using these methods, yielding better than 3% uniformity. The binary range modulator was programmed, optimized and characterized such that the proton field ranges were separated by approximately 5.0mm modulation width and delivered with an accuracy of 1.0mm in water. Several wobbling magnet scan patterns were evaluated and the raster pattern, spot spacing, scan amplitude and overscan margin were optimized for clinical use. Conclusion: Novel detectors and methods are required for clinically efficient optimization and characterization of proton beam scanning systems. Uniform scanning produces proton beam fields that are suited for clinical proton radiotherapy.

The rationale for intensity-modulated proton therapy in geometrically challenging cases

NASA Astrophysics Data System (ADS)

Safai, S.; Trofimov, A.; Adams, J. A.; Engelsman, M.; Bortfeld, T.

2013-09-01

Intensity-modulated proton therapy (IMPT) delivered with beam scanning is currently available at a limited number of proton centers. However, a simplified form of IMPT, the technique of field ‘patching’, has long been a standard practice in proton therapy centers. In field patching, different parts of the target volume are treated from different directions, i.e., a part of the tumor gets either full dose from a radiation field, or almost no dose. Thus, patching represents a form of binary intensity modulation. This study explores the limitations of the standard binary field patching technique, and evaluates possible dosimetric advantages of continuous dose modulations in IMPT. Specifics of the beam delivery technology, i.e., pencil beam scanning versus passive scattering and modulation, are not investigated. We have identified two geometries of target volumes and organs at risk (OAR) in which the use of field patching is severely challenged. We focused our investigations on two patient cases that exhibit these geometries: a paraspinal tumor case and a skull-base case. For those cases we performed treatment planning comparisons of three-dimensional conformal proton therapy (3DCPT) with field patching versus IMPT, using commercial and in-house software, respectively. We also analyzed the robustness of the resulting plans with respect to systematic setup errors of ±1 mm and range errors of ±2.5 mm. IMPT is able to better spare OAR while providing superior dose coverage for the challenging cases identified above. Both 3DCPT and IMPT are sensitive to setup errors and range uncertainties, with IMPT showing the largest effect. Nevertheless, when delivery uncertainties are taken into account IMPT plans remain superior regarding target coverage and OAR sparing. On the other hand, some clinical goals, such as the maximum dose to OAR, are more likely to be unmet with IMPT under large range errors. IMPT can potentially improve target coverage and OAR sparing in challenging cases, even when compared with the relatively complicated and time consuming field patching technique. While IMPT plans tend to be more sensitive to delivery uncertainties, their dosimetric advantage generally holds. Robust treatment planning techniques may further reduce the sensitivity of IMPT plans.

Introducing an on-line adaptive procedure for prostate image guided intensity modulate proton therapy.

PubMed

Zhang, M; Westerly, D C; Mackie, T R

2011-08-07

With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D(98%), D(50%) and D(2%) values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.

Introducing an on-line adaptive procedure for prostate image guided intensity modulate proton therapy

NASA Astrophysics Data System (ADS)

Zhang, M.; Westerly, D. C.; Mackie, T. R.

2011-08-01

With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D98%, D50% and D2% values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.

Protons in head-and-neck cancer: bridging the gap of evidence.

PubMed

Ramaekers, Bram L T; Grutters, Janneke P C; Pijls-Johannesma, Madelon; Lambin, Philippe; Joore, Manuela A; Langendijk, Johannes A

2013-04-01

To use Normal Tissue Complication Probability (NTCP) models and comparative planning studies to explore the (cost-)effectiveness of swallowing sparing intensity modulated proton radiotherapy (IMPT) compared with swallowing sparing intensity modulated radiotherapy with photons (IMRT) in head and neck cancer (HNC). A Markov model was constructed to examine and compare the costs and quality-adjusted life years (QALYs) of the following strategies: (1) IMPT for all patients; (2) IMRT for all patients; and (3) IMPT if efficient. The assumption of equal survival for IMPT and IMRT in the base case analysis was relaxed in a sensitivity analysis. Intensity modulated proton radiation therapy and IMRT for all patients yielded 6.620 and 6.520 QALYs and cost €50,989 and €41,038, respectively. Intensity modulated proton radiation therapy if efficient yielded 6.563 QALYs and cost €43,650. The incremental cost-effectiveness ratio of IMPT if efficient versus IMRT for all patients was €60,278 per QALY gained. In the sensitivity analysis, IMRT was more effective (0.967 QALYs) and less expensive (€8218) and thus dominated IMPT for all patients. Cost-effectiveness analysis based on normal tissue complication probability models and planning studies proved feasible and informative and enables the analysis of individualized strategies. The increased effectiveness of IMPT does not seem to outweigh the higher costs for all head-and-neck cancer patients. However, when assuming equal survival among both modalities, there seems to be value in identifying those patients for whom IMPT is cost-effective. Copyright © 2013 Elsevier Inc. All rights reserved.

WE-D-BRB-02: Proton Treatment Planning and Beam Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pankuch, M.

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, C.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-04: Clinical Applications of CBCT for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teo, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-01: Basic Physics of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arjomandy, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery.

PubMed

Takatori, Shingo; Hirai, Kazuhiro; Ozaki, Shuichiro; Tangsucharit, Panot; Fukushima-Miyashita, Satoko; Goda, Mitsuhiro; Hashikawa-Hobara, Narumi; Ono, Nobufumi; Kawasaki, Hiromu

2014-12-01

Previous studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid-1 (TRPV1) receptors located on calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon-axonal neurotransmission. Perfusion pressure and pH levels of perfusate in rat-perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively. Periarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long-lasting vasodilatation and decreased pH levels in the perfusate. Cold-storage denervation of the preparation abolished the decreased pH and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced vasoconstriction and effects on pH, but not PNS-induced vasodilatation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the PNS-induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long-lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca(2+) -free medium. These results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves. © 2014 The British Pharmacological Society.

Dosimetric characterization of a synthetic single crystal diamond detector in a clinical 62 MeV ocular therapy proton beam

NASA Astrophysics Data System (ADS)

Marinelli, Marco; Pompili, F.; Prestopino, G.; Verona, C.; Verona-Rinati, G.; Cirrone, G. A. P.; Cuttone, G.; La Rosa, R. M.; Raffaele, L.; Romano, F.; Tuvè, C.

2014-12-01

A synthetic single crystal diamond based Schottky photodiode was tested at INFN-LNS on the proton beam line (62 MeV) dedicated to the radiation treatment of ocular disease. The diamond detector response was studied in terms of pre-irradiation dose, linearity with dose and dose rate, and angular dependence. Depth dose curves were measured for the 62 MeV pristine proton beam and for three unmodulated range-shifted proton beams; furthermore, the spread-out Bragg peak was measured for a modulated therapeutic proton beam. Beam parameters, recommended by the ICRU report 78, were evaluated to analyze depth-dose curves from diamond detector. Measured dose distributions were compared with the corresponding dose distributions acquired with reference plane-parallel ionization chambers. Field size dependence of the output factor (dose per monitor unit) in a therapeutic modulated proton beam was measured with the diamond detector over the range of ocular proton therapy collimator diameters (5-30 mm). Output factors measured with the diamond detector were compared to the ones by a Markus ionization chamber, a Scanditronix Hi-p Si stereotactic diode and a radiochromic EBT2 film. Signal stability within 0.5% was demonstrated for the diamond detector with no need of any pre-irradiation dose. Dose and dose rate dependence of the diamond response was measured: deviations from linearity resulted to be within ±0.5% over the investigated ranges of 0.5-40.0 Gy and 0.3-30.0 Gy/min respectively. Output factors from diamond detector measured with the smallest collimator (5 mm in diameter) showed a maximum deviation of about 3% with respect to the high resolution radiochromic EBT2 film. Depth-dose curves measured by diamond for unmodulated and modulated beams were in good agreement with those from the reference plane-parallel Markus chamber, with relative differences lower than ±1% in peak-to-plateau ratios, well within experimental uncertainties. A 2.5% variation in diamond detector response was observed in angular dependence measurements carried-out by varying the proton beam incidence angle in the polar direction. The dosimetric characterization of the tested synthetic single crystal diamond detector clearly indicates its suitability for relative dosimetry in ocular therapy proton beams, with no need of any correction factors accounting for dose rate and linear energy transfer dependence.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design.

PubMed

Hofmann, Kerstin M; Masood, Umar; Pawelke, Joerg; Wilkens, Jan J

2015-09-01

Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and to determine limitations to comply with. Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10(8) and 8.3 × 10(9) to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10(9) and 2.9 × 10(9). The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ± 30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ± 10% fluctuations. Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hofmann, Kerstin M., E-mail: kerstin.hofmann@lrz.tu-muenchen.de; Wilkens, Jan J.; Masood, Umar

Purpose: Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and tomore » determine limitations to comply with. Methods: Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. Results: The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10{sup 8} and 8.3 × 10{sup 9} to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10{sup 9} and 2.9 × 10{sup 9}. The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ±30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ±10% fluctuations. Conclusions: Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.« less

An imaging informatics-based system utilizing DICOM objects for treating pain in spinal cord injury patients utilizing proton beam radiotherapy

NASA Astrophysics Data System (ADS)

Verma, Sneha K.; Liu, Brent J.; Chun, Sophia; Gridley, Daila S.

2014-03-01

Many US combat personnel have sustained nervous tissue trauma during service, which often causes Neuropathic pain as a side effect and is difficult to manage. However in select patients, synapse lesioning can provide significant pain control. Our goal is to determine the effectiveness of using Proton Beam radiotherapy for treating spinal cord injury (SCI) related neuropathic pain as an alternative to invasive surgical lesioning. The project is a joint collaboration of USC, Spinal Cord Institute VA Healthcare System, Long Beach, and Loma Linda University. This is first system of its kind that supports integration and standardization of imaging informatics data in DICOM format; clinical evaluation forms outcomes data and treatment planning data from the Treatment planning station (TPS) utilized to administer the proton therapy in DICOM-RT format. It also supports evaluation of SCI subjects for recruitment into the clinical study, which includes the development, and integration of digital forms and tools for automatic evaluation and classification of SCI pain. Last year, we presented the concept for the patient recruitment module based on the principle of Bayesian decision theory. This year we are presenting the fully developed patient recruitment module and its integration to other modules. In addition, the DICOM module for integrating DICOM and DICOM-RT-ION data is also developed and integrated. This allows researchers to upload animal/patient study data into the system. The patient recruitment module has been tested using 25 retrospective patient data and DICOM data module is tested using 5 sets of animal data.

Multi-Pulse Extraction from Los Alamos Proton Storage Ring for Radiographic Applications

NASA Astrophysics Data System (ADS)

Thiessen, Henry A.; Neri, Filippo; Rust, Kenneth R.; Redd, Dale B.

1997-05-01

For radiography of moving objects, two or more pulses with adjustable time spacing are required. The existing Proton Stotage Ring (PSR) extraction system is configured to extract the entire beam in a single turn. Two kickers and two kicker modulators fired at the same time perform the normal extraction function. By reconfiguring the two kickers and two modulators, it is possible to obtain two half-sized extraction kicks with adjustable time spacing. In this way, we have extracted two pulses with adjustable relative timing. The setup will be described and experimental results will be presented.

Comparison of acute proton, photon, and low-dose priming effects on genes associated with extracellular matrix and adhesion molecules in the lungs

PubMed Central

2013-01-01

Background Crew members on space missions inevitably are exposed to low background radiation and can receive much higher doses during solar particle events (SPE) that consist primarily of protons. Ionizing radiation could cause lung pathologies. Cell adhesion molecules (CAM) are believed to participate in fibrogenesis. Interactions between CAM and extracellular matrix (ECM) affect epithelial repair mechanisms in the lung. However, there are very limited data on biological effects of protons on normal lung tissue. Numerous reports have shown that exposure to low-dose/low-dose-rate (LDR) radiation can result in radioadaptation that renders cells more resistant to subsequent acute radiation. The goal of this study was to compare expression of genes associated with ECM and CAM, as well as critical profibrotic mediators, in mouse lungs after acute irradiation with photons and protons, and also determine whether pre-exposure to LDR γ-rays induces an adaptive effect. Results Overall, a marked difference was present in the proton vs. photon groups in gene expression. When compared to 0 Gy, more genes were affected by protons than by photons at both time points (11 vs. 6 on day 21 and 14 vs. 8 on day 56), and all genes affected by protons were upregulated. Many genes were modulated by LDR γ-rays when combined with photons or protons. Col1a1, mmp14, and mmp15 were significantly upregulated by all radiation regimens on day 21. Similarly, the change in expression of profibrotic proteins was also detected after acute and combination irradiation. Conclusion These data show that marked differences were present between acutely delivered protons and photons in modulating genes, and the effect of protons was more profound than that of photons. Pre-exposure to LDR γ-rays ‘normalized’ some genes that were modified by acute irradiation. PMID:23374750

SU-F-T-198: Dosimetric Comparison of Carbon and Proton Radiotherapy for Recurrent Nasopharynx Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Y; Zhao, J; Wang, W

2016-06-15

Purpose: Various radiotherapy planning methods for locally recurrent nasopharynx carcinoma (R-NPC) have been proposed. The purpose of this study was to compare carbon and proton therapy for the treatment of R-NPC in terms of dose coverage for target volume and sparing for organs at risk (OARs). Methods: Six patients who were suffering from R-NPC and treated using carbon therapy were selected for this study. Treatment plans with a total dose of 57.5Gy (RBE) in 23 fractions were made using SIEMENS Syngo V11. An intensity-modulated radiotherapy optimization method was chosen for carbon plans (IMCT) while for proton plans both intensity-modulated radiotherapymore » (IMPT) and single beam optimization (proton-SBO) methods were chosen. Dose distributions, dose volume parameters, and selected dosimetric indices for target volumes and OARs were compared for all treatment plans. Results: All plans provided comparable PTV coverage. The volume covered by 95% of the prescribed dose was comparable for all three plans. The average values were 96.11%, 96.24% and 96.11% for IMCT, IMPT, and proton-SBO respectively. A significant reduction of the 80% and 50% dose volumes were observed for the IMCT plans compared to the IMPT and proton-SBO plans. Critical organs lateral to the target such as brain stem and spinal cord were better spared by IMPT than by proton-SBO, while IMCT spared those organs best. For organs in the beam path, such as parotid glands, the mean dose results were similar for all three plans. Conclusion: Carbon plans yielded better dose conformity than proton plans. They provided similar or better target coverage while significantly lowering the dose for normal tissues. Dose sparing for critical organs in IMPT plans was better than proton-SBO, however, IMPT is known to be more sensitive to range uncertainties. For proton plans it is essential to find a balance between the two optimization methods.« less

4D CT-based Treatment Planning for Intensity-Modulated Radiation Therapy and Proton Therapy for Distal Esophagus Cancer

PubMed Central

Zhang, Xiaodong; Zhao, Kuai-Le; Guerrero, Thomas M.; McGuire, Sean E.; Yaremko, Brian; Komaki, Ritsuko; Cox, James D.; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D.; Mohan, Radhe; Liao, Zhongxing

2008-01-01

Purpose To compare three-dimensional (3D) and 4D computed tomography (CT)– based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Materials and Methods IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results Compared with IMRT, median lung volumes exposed to 5,10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%,5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%,8.4%,5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index CI=1.99) and greater irradiation of the heart (heart-V40=41.8%) compared with the IMRT plan(CI=1.55, heart-V40=35.7%) or the three-beam proton plan (CI=1.46, heart-V40=27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas-filling. Conclusions Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses. PMID:18722278

Four-dimensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal esophageal cancer.

PubMed

Zhang, Xiaodong; Zhao, Kuai-le; Guerrero, Thomas M; McGuire, Sean E; Yaremko, Brian; Komaki, Ritsuko; Cox, James D; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D; Mohan, Radhe; Liao, Zhongxing

2008-09-01

To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.

SU-F-T-175: Absorbed Dose Measurement Using Radiophotoluminescent Glass Dosimeter in Therapeutic Proton Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, W; National Institute of Radiological Sciences, Chiba, Chiba; Koba, Y

Purpose: To measure the absorbed dose to water Dw in therapeutic proton beam with radiophotoluminescent glass dosimeter (RGD), a methodology was proposed. In this methodology, the correction factor for the LET dependence of radiophotoluminescent (RPL) efficiency and the variation of mass stopping power ratio of water to RGD (SPRw, RGD) were adopted. The feasibility of proposed method was evaluated in this report. Methods: The calibration coefficient in terms of Dw for RGDs (GD-302M, Asahi Techno Glass) was obtained using 60Co beam. The SPRw, RGD was calculated by Monte Carlo simulation toolkit Geant4. The LET dependence of RPL efficiency was investigatedmore » experimentally by using a 70 MeV proton beam at National Institute of Radiological Sciences. For clinical usage, the residual range Rres was used as a quality index to determine the correction factor for RPL efficiency. The proposed method was evaluated by measuring Dw at difference depth in the 200 MeV proton beam. Results: For both modulated and non-modulated proton beam, the SPRw, RGD increases more than 3 % where Rres are less than 1 cm. RPL efficiency decreases with increasing LET and it reaches 0.6 at LET of 10 keV µm{sup −1}. Dw measured by RGD (Dw, RGD) shows good agreement with that measured by ionization chamber (Dw, IC) and the relative difference between Dw, RGD and Dw, IC are within 3 % where Rres is larger than 1 cm. Conclusion: In this work, a methodology for using RGD in proton dosimetry was proposed and the SPRw, RGD and the LET dependence of RPL efficiency in therapeutic proton beam was investigated. The results revealed that the proposed method is useful for RGD in the dosimetry of proton beams.« less

Technique for comprehensive head and neck irradiation using 3-dimensional conformal proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, IN; Walter, Alexander S.

2015-01-01

Owing to the technical and logistical complexities of matching photon and proton treatment modalities, we developed and implemented a technique of comprehensive head and neck radiation using 3-dimensional (3D) conformal proton therapy. A monoisocentric technique was used with a 30-cm snout. Cervical lymphatics were treated with 3 fields: a posterior-anterior field with a midline block and a right and a left posterior oblique field. The matchline of the 3 cervical nodal fields with the primary tumor site fields was staggered by 0.5 cm. Comparative intensity-modulated photon plans were later developed for 12 previously treated patients to provide equivalent target coverage,more » while matching or improving on the proton plans' sparing of organs at risk (OARs). Dosimetry to OARs was evaluated and compared by treatment modality. Comprehensive head and neck irradiation using proton therapy yielded treatment plans with significant dose avoidance of the oral cavity and midline neck structures. When compared with the generated intensity-modulated radiation therapy (IMRT) plans, the proton treatment plans yielded statistically significant reductions in the mean and integral radiation dose to the oral cavity, larynx, esophagus, and the maximally spared parotid gland. There was no significant difference in mean dose to the lesser-spared parotid gland by treatment modality or in mean or integral dose to the spared submandibular glands. A technique for cervical nodal irradiation using 3D conformal proton therapy with uniform scanning was developed and clinically implemented. Use of proton therapy for cervical nodal irradiation resulted in large volume of dose avoidance to the oral cavity and low dose exposure to midline structures of the larynx and the esophagus, with lower mean and integral dose to assessed OARs when compared with competing IMRT plans.« less

High energy proton induced radiation damage of rare earth permanent magnet quadrupoles.

PubMed

Schanz, M; Endres, M; Löwe, K; Lienig, T; Deppert, O; Lang, P M; Varentsov, D; Hoffmann, D H H; Gutfleisch, O

2017-12-01

Permanent magnet quadrupoles (PMQs) are an alternative to common electromagnetic quadrupoles especially for fixed rigidity beam transport scenarios at particle accelerators. Using those magnets for experimental setups can result in certain scenarios, in which a PMQ itself may be exposed to a large amount of primary and secondary particles with a broad energy spectrum, interacting with the magnetic material and affecting its magnetic properties. One specific scenario is proton microscopy, where a proton beam traverses an object and a collimator in which a part of the beam is scattered and deflected into PMQs used as part of a diagnostic system. During the commissioning of the PRIOR (Proton Microscope for Facility for Antiproton and Ion Research) high energy proton microscope facility prototype at Gesellschaft für Schwerionenforschung in 2014, a significant reduction of the image quality was observed which was partially attributed to the demagnetization of the used PMQ lenses and the corresponding decrease of the field quality. In order to study this phenomenon, Monte Carlo simulations were carried out and spare units manufactured from the same magnetic material-single wedges and a fully assembled PMQ module-were deliberately irradiated by a 3.6 GeV intense proton beam. The performed investigations have shown that in proton radiography applications the above described scattering may result in a high irradiation dose in the PMQ magnets. This did not only decrease the overall magnetic strength of the PMQs but also caused a significant degradation of the field quality of an assembled PMQ module by increasing the parasitic multipole field harmonics which effectively makes PMQs impractical for proton radiography applications or similar scenarios.

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

Volumetric Modulated Arc Radiotherapy for Vestibular Schwannomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lagerwaard, Frank J.; Meijer, Otto W.M.; Hoorn, Elles A.P. van der

2009-06-01

Purpose: To evaluate volumetric modulated arc radiotherapy (RapidArc [RA]), a novel approach allowing for rapid treatment delivery, for the treatment of vestibular schwannoma (VS). Methods and Materials: The RA plans were generated for a small (0.5 cm{sup 3}), intermediate (2.8 cm{sup 3}), and large (14.8 cm{sup 3}) VS. The prescription dose was 12.5 Gy to the encompassing 80% isodose. The RA plans were compared with conventional radiosurgery plans using both a single dynamic conformal arc (1DCA) and five noncoplanar dynamic conformal arcs (5DCA). Conformity indices (CI) and dose-volume histograms of critical organs were compared. The RA plan for the medium-sizedmore » VS was measured in a phantom using Gafchromic EBT films and compared with calculated dose distributions. Results: The RA planning was completed within 30 min in all cases, and calculated treatment delivery time (after patient setup) was 5 min vs. 20 min for 5DCA. A superior CI was achieved with RA, with a substantial decrease in low-dose irradiation of the normal brain achieved relative to 5DCA plans. Maximum doses to critical organs were similar for RA and 5DCA but were higher for 1DCA. Film measurements showed the differences between calculated and measured doses to be smaller than 1.5% in the high-dose area and smaller than 3% in the low-dose area. Conclusion: The RA plans consistently achieved a higher CI and decrease in areas of low-dose irradiation. This, together with shorter treatment delivery times, has led to RA replacing our conventional five-arc radiosurgery technique for VS.« less

Depth Dose Measurement using a Scintillating Fiber Optic Dosimeter for Proton Therapy Beam of the Passive-Scattering Mode Having Range Modulator Wheel

NASA Astrophysics Data System (ADS)

Hwang, Ui-Jung; Shin, Dongho; Lee, Se Byeong; Lim, Young Kyung; Jeong, Jong Hwi; Kim, Hak Soo; Kim, Ki Hwan

2018-05-01

To apply a scintillating fiber dosimetry system to measure the range of a proton therapy beam, a new method was proposed to correct for the quenching effect on measuring an spread out Bragg peak (SOBP) proton beam whose range is modulated by a range modulator wheel. The scintillating fiber dosimetry system was composed of a plastic scintillating fiber (BCF-12), optical fiber (SH 2001), photo multiplier tube (H7546), and data acquisition system (PXI6221 and SCC68). The proton beam was generated by a cyclotron (Proteus-235) in the National Cancer Center in Korea. It operated in the double-scattering mode and the spread out of the Bragg peak was achieved by a spinning range modulation wheel. Bragg peak beams and SOBP beams of various ranges were measured, corrected, and compared to the ion chamber data. For the Bragg peak beam, quenching equation was used to correct the quenching effect. On the proposed process of correcting SOBP beams, the measured data using a scintillating fiber were separated by the Bragg peaks that the SOBP beam contained, and then recomposed again to reconstruct an SOBP after correcting for each Bragg peak. The measured depth-dose curve for the single Bragg peak beam was well corrected by using a simple quenching equation. Correction for SOBP beam was conducted with a newly proposed method. The corrected SOBP signal was in accordance with the results measured with an ion chamber. We propose a new method to correct for the SOBP beam from the quenching effect in a scintillating fiber dosimetry system. This method can be applied to other scintillator dosimetry for radiation beams in which the quenching effect is shown in the scintillator.

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaudhary, Pankaj; Marshall, Thomas I.; Perozziello, Francesca M.

2014-09-01

Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate themore » RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.« less

Technique for measurement of energy loss of proton in target medium

NASA Astrophysics Data System (ADS)

Khadke, U. V.

2018-05-01

Energy loss (EL) of charged particles in target medium needs special attention, when measurements are required to be done repeatedly over periods of couple of days. It is imperative to ensure that the measurements are not affected by the long term drifts of the accelerator beam energy and the associated electronic modules. For one such situation in measurement of EL of proton beam in thick target, we optimised and standardized the technique of measuring most probable energy loss of 24.774 MeV proton in aluminium target of thickness 330 mg/cm2. The paper described the method that we developed to ensure that our EL measurements were free from effects of drifts due to any associated electronic modules. The details of the energy spectrometer, basic principle and technique for energy loss measurements in target medium are described in this paper.

Modulation of cosmic-ray protons and helium nuclei near solar maximum

NASA Technical Reports Server (NTRS)

Rygg, T. A.; Ogallagher, J. J.; Earl, J. A.

1974-01-01

Balloon observations of proton and helium spectra in 1970, 1971 and 1972, reveal a factor of approximately 1.85 deviation from a single valued regression at low rigidities. This deviation decreases with increasing rigidity for both species. The period 1969-1970 is unique because time variations at low and high energies were anti-correlated. When satellite observations are used to extend the balloon observations to energies below 100 MeV/Nucleon, the proton spectrum showed a steeper slope in 1970 and 1972 than the characteristic J = AT spectrum observed during 1965-1969. The slope of the helium spectrum became continuously flatter during the same period (1970-1972). Computer generated spectra based on simple two parameter modulation models describe the basic features of the observations if one of the variable parameters is used to characterize the rigidity dependence of the diffusion coefficient. Models which do not allow such a variation are not consistent with the observations.

Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam, E-mail: yadav@humonc.wisc.edu; Department of Medical Physics, University of Wisconsin, Madison, WI; University of Wisconsin Riverview Cancer Center, Wisconsin Rapids, WI

2013-10-01

Chondrosarcomas are relatively radiotherapy resistant, and also delivering high radiation doses is not feasible owing to anatomic constraints. In this study, the feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic spine is explored and compared with other available photon and proton radiotherapy techniques in the clinical setting. A patient was treated for high-grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively, the tomotherapy plan was compared with intensity-modulated radiation therapy, dynamic arc photon therapy, and proton therapy. Two primary comparisons were made: (1) comparison of normal tissue sparing with comparable target volume coverage (plan-1), and (2) comparison ofmore » target volume coverage with a constrained maximum dose to the cord center (plan-2). With constrained target volume coverage, proton plans were found to yield lower mean doses for all organs at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning resulted in the lowest mean dose to all organs at risk amongst photon-based methods. For cord dose constrained plans, the static-field intensity-modulated radiation therapy and dynamic arc plans resulted target underdosing in 20% and 12% of planning target volume2 volumes, respectively, whereas both proton and tomotherapy plans provided clinically acceptable target volume coverage with no portion of planning target volume2 receiving less than 90% of the prescribed dose. Tomotherapy plans are comparable to proton plans and produce superior results compared with other photon modalities. This feasibility study suggests that tomotherapy is an attractive alternative to proton radiotherapy for delivering high doses to lesions in the thoracic spine.« less

Energy spectrum control for modulated proton beams.

PubMed

Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N

2009-06-01

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

ISS General Resource Reel

NASA Technical Reports Server (NTRS)

1998-01-01

This video is a collection of computer animations and live footage showing the construction and assembly of the International Space Station (ISS). Computer animations show the following: (1) ISS fly around; (2) ISS over a sunrise seen from space; (3) the launch of the Zarya Control Module; (4) a Proton rocket launch; (5) the Space Shuttle docking with Zarya and attaching Zarya to the Unity Node; (6) the docking of the Service Module, Zarya, and Unity to Soyuz; (7) the Space Shuttle docking to ISS and installing the Z1 Truss segment and the Pressurized Mating Adapter (PMA); (8) Soyuz docking to the ISS; (9) the Transhab components; and (10) a complete ISS assembly. Live footage shows the construction of Zarya, the Proton rocket, Unity Node, PMA, Service Module, US Laboratory, Italian Multipurpose Logistics Module, US Airlock, and the US Habitation Module. STS-88 Mission Specialists Jerry Ross and James Newman are seen training in the Neutral Buoyancy Laboratory (NBL). The Expedition 1 crewmembers, William Shepherd, Yuri Gidzenko, and Sergei Krikalev, are shown training in the Black Sea and at Johnson Space Flight Center for water survival.

Continuous ECS-indicated recording of the proton-motive charge flux in leaves.

PubMed

Klughammer, Christof; Siebke, Katharina; Schreiber, Ulrich

2013-11-01

Technical features and examples of application of a special emitter-detector module for highly sensitive measurements of the electrochromic pigment absorbance shift (ECS) via dual-wavelength (550-520 nm) transmittance changes (P515) are described. This device, which has been introduced as an accessory of the standard, commercially available Dual-PAM-100 measuring system, not only allows steady-state assessment of the proton motive force (pmf) and its partitioning into ΔpH and ΔΨ components, but also continuous recording of the overall charge flux driven by photosynthetic light reactions. The new approach employs a double-modulation technique to derive a continuous signal from the light/dark modulation amplitude of the P515 signal. This new, continuously measured signal primarily reflects the rate of proton efflux via the ATP synthase, which under quasi-stationary conditions corresponds to the overall rate of proton influx driven by coupled electron transport. Simultaneous measurements of charge flux and CO2 uptake as a function of light intensity indicated a close to linear relationship in the light-limited range. A linear relationship between these two signals was also found for different internal CO2 concentrations, except for very low CO2, where the rate of charge flux distinctly exceeded the rate of CO2 uptake. Parallel oscillations in CO2 uptake and charge flux were induced by high CO2 and O2. The new device may contribute to the elucidation of complex regulatory mechanisms in intact leaves.

Detecting Low-Contrast Features in the Cosmic Ray Albedo Proton Map of the Moon

NASA Technical Reports Server (NTRS)

Wilson, J. K.; Schwadron, N.; Spence, H. E.; Golightly, M. J.; Case, A. W.; Smith, S.; Blake, J. B.; Kasper, J.; Looper, M. D.; Mazur, J. E.;

Initial experience of ArcCHECK and 3DVH software for RapidArc treatment plan verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Infusino, Erminia; Mameli, Alessandra, E-mail: e.infusino@unicampus.it; Conti, Roberto

2014-10-01

The purpose of this study was to perform delivery quality assurance with ArcCHECK and 3DVH system (Sun Nuclear, FL) and to evaluate the suitability of this system for volumetric-modulated arc therapy (VMAT) (RapidArc [RA]) verification. This software calculates the delivered dose distributions in patients by perturbing the calculated dose using errors detected in fluence or planar dose measurements. The device is tested to correlate the gamma passing rate (%GP) and the composite dose predicted by 3DVH software. A total of 28 patients with prostate cancer who were treated with RA were analyzed. RA treatments were delivered to a diode arraymore » phantom (ArcCHECK), which was used to create a planned dose perturbation (PDP) file. The 3DVH analysis used the dose differences derived from comparing the measured dose with the treatment planning system (TPS)-calculated doses to perturb the initial TPS-calculated dose. The 3DVH then overlays the resultant dose on the patient's structures using the resultant “PDP” beams. Measured dose distributions were compared with the calculated ones using the gamma index (GI) method by applying the global (Van Dyk) normalization and acceptance criteria, i.e., 3%/3 mm. Paired differences tests were used to estimate statistical significance of the differences between the composite dose calculated using 3DVH and %GP. Also, statistical correlation by means of logistic regression analysis has been analyzed. Dose-volume histogram (DVH) analysis for patient plans revealed small differences between treatment plan calculations and 3DVH results for organ at risk (OAR), whereas planning target volume (PTV) of the measured plan was systematically higher than that predicted by the TPS. The t-test results between the planned and the estimated DVH values showed that mean values were incomparable (p < 0.05). The quality assurance (QA) gamma analysis 3%/3 mm showed that in all cases there were only weak-to-moderate correlations (Pearson r: 0.12 to 0.74). Moreover, clinically relevant differences increased with increasing QA passing rate, indicating that some of the largest dose differences occurred in the cases of high QA passing rates, which may be called “false negatives.” The clinical importance of any disagreement between the measured and the calculated dose is often difficult to interpret; however, beam errors (either in delivery or in TPS calculation) can affect the effectiveness of the patient dose. Further research is needed to determinate the role of a PDP-type algorithm to accurately estimate patient dose effect.« less

SU-E-T-139: Feasibility Study of Glass Dosimeter for in Vivo Measurement: Dosimetric Characterization and Clinical Application in Proton Beams.

PubMed

Lah, J; Kim, D; Park, S

2012-06-01

To evaluate the suitability of the GD-301 glass dosimeter for use in in vivo dose verification in proton therapy. The glass dosimeter was analyzed for its dosimetric characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stair-like holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and TLD dose measurements of plan delivery using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with a varying separation between the target volume and the surface of 6 patients. Uniformity was within 1.5%. The dose-response has a good linear. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in non-modulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the Eclipse and that of the measured by the glass dosimeter was within 5%. In vivo dosimetry of patients, given the results of the glass dosimeter and TLD measurements, calculated doses on the surface of the patient are typically overestimated between 4% and 16%. As such, it is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential to be used for in vivo patient proton dosimetry. © 2012 American Association of Physicists in Medicine.

Whole-Brain Radiotherapy With Simultaneous Integrated Boost to Multiple Brain Metastases Using Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lagerwaard, Frank J.; Hoorn, Elles A.P. van der; Verbakel, Wilko

2009-09-01

Purpose: Volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) allows for the generation of intensity-modulated dose distributions by use of a single gantry rotation. We used RA to plan and deliver whole-brain radiotherapy (WBRT) with a simultaneous integrated boost in patients with multiple brain metastases. Methods and Materials: Composite RA plans were generated for 8 patients, consisting of WBRT (20 Gy in 5 fractions) with an integrated boost, also 20 Gy in 5 fractions, to Brain metastases, and clinically delivered in 3 patients. Summated gross tumor volumes were 1.0 to 37.5 cm{sup 3}. RA plans weremore » measured in a solid water phantom by use of Gafchromic films (International Specialty Products, Wayne, NJ). Results: Composite RA plans could be generated within 1 hour. Two arcs were needed to deliver the mean of 1,600 monitor units with a mean 'beam-on' time of 180 seconds. RA plans showed excellent coverage of planning target volume for WBRT and planning target volume for the boost, with mean volumes receiving at least 95% of the prescribed dose of 100% and 99.8%, respectively. The mean conformity index was 1.36. Composite plans showed much steeper dose gradients outside Brain metastases than plans with a conventional summation of WBRT and radiosurgery. Comparison of calculated and measured doses showed a mean gamma for double-arc plans of 0.30, and the area with a gamma larger than 1 was 2%. In-room times for clinical RA sessions were approximately 20 minutes for each patient. Conclusions: RA treatment planning and delivery of integrated plans of WBRT and boosts to multiple brain metastases is a rapid and accurate technique that has a higher conformity index than conventional summation of WBRT and radiosurgery boost.« less

Energetic particles in the pre-dawn magnetotail of Jupiter

NASA Technical Reports Server (NTRS)

Schardt, A. W.; Mcdonald, F. B.; Trainor, J. H.

1980-01-01

A detailed account is given of the energetic electron and proton populations as observed with Voyagers 1 and 2 during their passes through the dawn magnetotail of Jupiter. The region between 20 and 150 R sub J is dominated by a thin plasma sheet, where trapped energetic electron and proton fluxes reach their maximum. Proton spectra can be represented by an exponential in rigidity with a characteristic energy of approximately 50 keV. Proton anisotropies were consistent with corotation even at 100 R sub J. A major proton acceleration event as well as several cases of field aligned proton streaming were observed. The flux of 0.4 MeV protons decreases by three orders of magnitude between 30 and 90 R sub J and then remains relatively constant to the magnetopause. Fine structure in the data indicate longitudinal asymmetries with respect to the dipole orientation. Electron spectra in the magnetosheath and interplanetary space are modulated by the Jovian longitude relative to the subsolar point.

Predictions of secondary neutrons and their importance to radiation effects inside the International Space Station

NASA Technical Reports Server (NTRS)

Armstrong, T. W.; Colborn, B. L.

2001-01-01

As part of a study funded by NASA MSFC to assess thecontribution of secondary particles in producing radiation damage to optoelectronics devices located on the International Space Station (IS), Monte Carlo calculations have been made to predict secondary spectra vs. shielding inside ISS modules and in electronics boxes attached on the truss (Armstrong and Colborn, 1998). The calculations take into account secondary neutron, proton, and charged pion production from the ambient galactic cosmic-ray (GCR) proton, trapped proton, and neutron albedo environments. Comparisons of the predicted neutron spectra with measurments made on the Mir space station and other spacecraft have also been made (Armstrong and Colborn, 1998). In this paper, some initial results from folding the predicted neutron spectrum inside ISS modules from Armstrong and Colborn (1998) with several types of radiation effects response functions related to electronics damage and astronaut-dose are given. These results provide an estimate of the practical importance of neutrons compared to protons in assessing radiation effects for the ISS. Also, the important neutron energy ranges for producing these effects have been estimated, which provides guidance for onboard neutron measurement requirements.

SOLARPROP: Charge-sign dependent solar modulation for everyone

NASA Astrophysics Data System (ADS)

Kappl, Rolf

2016-10-01

We present SOLARPROP, a tool to compute the influence of charge-sign dependent solar modulation for cosmic ray spectra. SOLARPROP is able to use the output of popular tools like GALPROP or DRAGON and offers the possibility to embed new models for solar modulation. We present some examples for proton, antiproton and positron fluxes in the light of the recent PAMELA and AMS-02 data.

Improvement of kink characteristic of proton-implanted VCSEL with ITO overcoating

NASA Astrophysics Data System (ADS)

Lai, Fang-I.; Chang, Ya-Hsien; Laih, Li-Hong; Kuo, Hao-chung; Wang, S. C.

2004-06-01

Proton implanted VCSEL has been demonstrated with good reliability and decent modulation speed up to 1.25 Gb/s. However, kinks in current vs light output (L-I) has been always an issue in the gain-guided proton implant VCSEL. The kink related jitter and noise performance made it difficult to meet 2.5 Gb/s (OC-48) requirement. The kinks in L-I curve can be attributed to non-uniform carrier distribution induced non-uniform gain distribution within emission area. In this paper, the effects of a Ti/ITO transparent over-coating on the proton-implanted AlGaAs/GaAs VCSELs (15um diameter aperture) are investigated. The kinks distribution in L-I characteristics from a 2 inch wafer is greatly improved compared to conventional process. These VCSELs exhibit nearly kink-free L-I output performance with threshold currents ~3 mA, and the slope efficiencies ~ 0.25 W/A. The near-field emission patterns suggest the Ti/ITO over-coating facilitates the current spreading and uniform carrier distribution of the top VCSEL contact thus enhancing the laser performance. Finally, we performed high speed modulation measurement. The eye diagram of proton-implanted VCSELs with Ti/ITO transparent over-coating operating at 2.125 Gb/s with 10mA bias and 9dB extinction ratio shows very clean eye with jitter less than 35 ps.

Intensity-Modulated or Proton Radiation Therapy for Sinonasal Malignancy

ClinicalTrials.gov

2018-02-13

Adenoid Cystic Carcinoma; Squamous Cell Carcinoma; Sinonasal Carcinoma; Sinonasal Undifferentiated Carcinoma; Mucoepidermoid Carcinoma; Schneiderian Carcinoma; Myoepithelial Carcinoma; Esthesioneuroblastoma; Melanoma

Coherent transition radiation from a self-modulated charged particle beam

NASA Astrophysics Data System (ADS)

Xu, X.; Yu, P.; An, W.; Lu, W.; Mori, W. B.

2012-12-01

Plasma wakefield accelerator utilizing a TeV proton beam is a promising method to generate a TeV electron beam. However the length of the existing proton beam is too long compared with the proper plasma skin depth. As a result selfmodulation instability takes place after such a long pulse enters into the plasma. The transverse spot size of the long beam changes periodically in the longitudinal direction. Therefor measurement of the coherent transition radiation when the selfmodulated beam leaves the plasma is a possible method to demonstrate the self-modulation instability. In this paper, we analyze the angular spectrum of this coherent transition radiation when the beam comes from plasma to vacuum.

Remote modulation of singlet-triplet gaps in carbenes

NASA Astrophysics Data System (ADS)

Alkorta, Ibon; Montero-Campillo, M. Merced; Elguero, José

2018-02-01

The modulation of the singlet-triplet (S/T) gap of phenyl-carbene derivatives by hydrogen bond formation has been studied using the G4(MP2) computational method. The complexation of the aromatic ring substituents (-NH2, -OH, -PH2, -SH) in meta- and para-positions with water and the protonation or deprotonation of such groups have a remarkable influence on the S/T gaps, reaching S/T gap variations from 25.7 to 93.7 kJ mol-1. This variation is linearly related to the binding energy difference of the S/T configurations. Importantly, the triplet and singlet electronic configurations are systematically favored in the protonated and deprotonated forms, respectively, in all cases.

Investigation of EBT2 and EBT3 films for proton dosimetry in the 4-20 MeV energy range.

PubMed

Reinhardt, S; Würl, M; Greubel, C; Humble, N; Wilkens, J J; Hillbrand, M; Mairani, A; Assmann, W; Parodi, K

2015-03-01

Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose determination in radiation therapy because they offer a superior spatial resolution compared to any other digital dosimetric 2D detector array. The possibility to detect steep dose gradients is not only attractive for intensity-modulated radiation therapy with photons but also for intensity-modulated proton therapy. Their characteristic dose rate-independent response makes radiochromic films also attractive for dose determination in cell irradiation experiments using laser-driven ion accelerators, which are currently being investigated as future medical ion accelerators. However, when using these films in ion beams, the energy-dependent dose response in the vicinity of the Bragg peak has to be considered. In this work, the response of these films for low-energy protons is investigated. To allow for reproducible and background-free irradiation conditions, the films were exposed to mono-energetic protons from an electrostatic accelerator, in the 4-20 MeV energy range. For comparison, irradiation with clinical photons was also performed. It turned out that in general, EBT2 and EBT3 films show a comparable performance. For example, dose-response curves for photons and protons with energies as low as 11 MeV show almost no differences. However, corrections are required for proton energies below 11 MeV. Care has to be taken when correction factors are related to an average LET from depth-dose measurements, because only the dose-averaged LET yields similar results as obtained in mono-energetic measurements.

Poster - 31: Predicting IQ and hearing loss following radiotherapy in pediatric brain tumors: proton vs photon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortin, Dominique; Ng, Angela; Tsang, Derek

Purpose: The increased sparing of normal tissues in intensity modulated proton therapy (IMPT) in pediatric brain tumor treatments should translate into improved neurocognitive outcomes. Models were used to estimate the intelligence quotient (IQ) and the risk of hearing loss 5 years post radiotherapy and to compare outcomes of proton against photon in pediatric brain tumors. Methods: Patients who had received intensity modulated radiotherapy (IMRT) were randomly selected from our retrospective database. The existing planning CT and contours were used to generate IMPT plans. The RBE-corrected dose was calculated for both IMPT and IMRT. For each patient, the IQ was estimatedmore » via a Monte Carlo technique, whereas the reported incidence of hearing loss as a function of cochlear dose was used to estimate the probability of occurrence. Results: The integrated brain dose was reduced in all IMPT plans, translating into a gain of 2 IQ points on average for protons for the whole cohort at 5 years post-treatment. In terms of specific diseases, the gains in IQ ranged from 0.8 points for medulloblastoma, to 2.7 points for craniopharyngioma. Hearing loss probability was evaluated on a per-ear-basis and was found to be systematically less for proton versus photon: overall 2.9% versus 7.2%. Conclusions: A method was developed to predict IQ and hearing outcomes in pediatric brain tumor patients on a case-by-case basis. A modest gain was systematically observed for proton in all patients. Given the uncertainties within the model used and our reinterpretation, these gains may be underestimated.« less

Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

PubMed Central

Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

2015-01-01

Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (p<0.01) compared to photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. Lung V20 and mean lung dose decreased 18% (p<0.01) and 36% (p<0.01), respectively, with proton IFRT and 11% (p=0.03) and 26% (p<0.01) with ENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all p<0.01). Conclusions This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

PubMed

Kesarwala, Aparna H; Ko, Christine J; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E; O'Meara, William P; Simone, Charles B; Rengan, Ramesh

2015-05-01

Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. Published by Elsevier Inc.

The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification

PubMed Central

Starkus, John G; Fleig, Andrea; Penner, Reinhold

2010-01-01

TRPM2 is a calcium-permeable non-selective cation channel expressed in the plasma membrane and in lysosomes that is critically involved in aggravating reactive oxygen species (ROS)-induced inflammatory processes and has been implicated in cell death. TRPM2 is gated by ADP-ribose (ADPR) and modulated by physiological processes that produce peroxide, cyclic ADP-ribose (cADPR), nicotinamide adenine dinucleotide phosphate (NAADP) and Ca2+. We investigated the role of extra- and intracellular acidification on heterologously expressed TRPM2 in HEK293 cells. Our results show that TRPM2 is inhibited by external acidification with an IC50 of pH 6.5 and is completely suppressed by internal pH of 6. Current inhibition requires channel opening and is strongly voltage dependent, being most effective at negative potentials. In addition, increased cytosolic pH buffering capacity or elevated [Ca2+]i reduces the rate of current inactivation elicited by extracellular acidification, and Na+ and Ca2+ influence the efficacy of proton-induced inactivation. Together, these results suggest that external protons permeate TRPM2 channels to gain access to an intracellular site that regulates channel activity. Consistent with this notion, single-channel measurements in HEK293 cells reveal that internal protons induce channel closure without affecting single-channel conductance, whereas external protons affect channel open probability as well as single-channel conductance of native TRPM2 in neutrophils. We conclude that protons compete with Na+ and Ca2+ for channel permeation and channel closure results from a competitive antagonism of protons at an intracellular Ca2+ binding site. PMID:20194125

The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification.

PubMed

Starkus, John G; Fleig, Andrea; Penner, Reinhold

2010-04-15

TRPM2 is a calcium-permeable non-selective cation channel expressed in the plasma membrane and in lysosomes that is critically involved in aggravating reactive oxygen species (ROS)-induced inflammatory processes and has been implicated in cell death. TRPM2 is gated by ADP-ribose (ADPR) and modulated by physiological processes that produce peroxide, cyclic ADP-ribose (cADPR), nicotinamide adenine dinucleotide phosphate (NAADP) and Ca(2+). We investigated the role of extra- and intracellular acidification on heterologously expressed TRPM2 in HEK293 cells. Our results show that TRPM2 is inhibited by external acidification with an IC(50) of pH 6.5 and is completely suppressed by internal pH of 6. Current inhibition requires channel opening and is strongly voltage dependent, being most effective at negative potentials. In addition, increased cytosolic pH buffering capacity or elevated [Ca(2+)](i) reduces the rate of current inactivation elicited by extracellular acidification, and Na(+) and Ca(2+) influence the efficacy of proton-induced inactivation. Together, these results suggest that external protons permeate TRPM2 channels to gain access to an intracellular site that regulates channel activity. Consistent with this notion, single-channel measurements in HEK293 cells reveal that internal protons induce channel closure without affecting single-channel conductance, whereas external protons affect channel open probability as well as single-channel conductance of native TRPM2 in neutrophils. We conclude that protons compete with Na(+) and Ca(2+) for channel permeation and channel closure results from a competitive antagonism of protons at an intracellular Ca(2+) binding site.

Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer

DOE PAGES

Michalczyk, Ryszard; Unkefer, Clifford J.; Bacik, John -Paul; ...

2015-05-05

Proton transfer is a fundamental mechanism at the core of many enzyme-catalyzed reactions. It is also exquisitely sensitive to a number of factors, including pH, electrostatics, proper active-site geometry, and chemistry. Carbonic anhydrase has evolved a fast and efficient way to conduct protons through a combination of hydrophilic amino acid side chains that coordinate a highly ordered H-bonded water network. This study uses a powerful approach, combining NMR solution studies with neutron protein crystallography, to determine the effect of pH and divalent cations on key residues involved in proton transfer in human carbonic anhydrase. Lastly, the results have broad implicationsmore » for our understanding of proton transfer and how subtle changes in ionization and H-bonding interactions can modulate enzyme catalysis.« less

Sparsity constrained split feasibility for dose-volume constraints in inverse planning of intensity-modulated photon or proton therapy

NASA Astrophysics Data System (ADS)

Penfold, Scott; Zalas, Rafał; Casiraghi, Margherita; Brooke, Mark; Censor, Yair; Schulte, Reinhard

2017-05-01

A split feasibility formulation for the inverse problem of intensity-modulated radiation therapy treatment planning with dose-volume constraints included in the planning algorithm is presented. It involves a new type of sparsity constraint that enables the inclusion of a percentage-violation constraint in the model problem and its handling by continuous (as opposed to integer) methods. We propose an iterative algorithmic framework for solving such a problem by applying the feasibility-seeking CQ-algorithm of Byrne combined with the automatic relaxation method that uses cyclic projections. Detailed implementation instructions are furnished. Functionality of the algorithm was demonstrated through the creation of an intensity-modulated proton therapy plan for a simple 2D C-shaped geometry and also for a realistic base-of-skull chordoma treatment site. Monte Carlo simulations of proton pencil beams of varying energy were conducted to obtain dose distributions for the 2D test case. A research release of the Pinnacle 3 proton treatment planning system was used to extract pencil beam doses for a clinical base-of-skull chordoma case. In both cases the beamlet doses were calculated to satisfy dose-volume constraints according to our new algorithm. Examination of the dose-volume histograms following inverse planning with our algorithm demonstrated that it performed as intended. The application of our proposed algorithm to dose-volume constraint inverse planning was successfully demonstrated. Comparison with optimized dose distributions from the research release of the Pinnacle 3 treatment planning system showed the algorithm could achieve equivalent or superior results.

Unraveling the mechanism of proton translocation in the extracellular half-channel of bacteriorhodopsin.

PubMed

Ge, Xiaoxia; Gunner, M R

2016-05-01

Bacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85, and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation states of the SB216, D85, D212, and E204. The side-chain orientation of R82 is determined primarily by the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen-bond network and consequently possible pathways of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system show that proton transfer via a guanidinium group requires an initial geometry permitting proton donation and acceptance by the same amine. In all the bacteriorhodopsin models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O' state where the proton on D85 is transferred to D212. © 2016 Wiley Periodicals, Inc.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Organic/inorganic hybrid synaptic transistors gated by proton conducting methylcellulose films

NASA Astrophysics Data System (ADS)

Wan, Chang Jin; Zhu, Li Qiang; Wan, Xiang; Shi, Yi; Wan, Qing

2016-01-01

The idea of building a brain-inspired cognitive system has been around for several decades. Recently, electric-double-layer transistors gated by ion conducting electrolytes were reported as the promising candidates for synaptic electronics and neuromorphic system. In this letter, indium-zinc-oxide transistors gated by proton conducting methylcellulose electrolyte films were experimentally demonstrated with synaptic plasticity including paired-pulse facilitation and spatiotemporal-correlated dynamic logic. More importantly, a model based on proton-related electric-double-layer modulation and stretched-exponential decay function was proposed, and the theoretical results are in good agreement with the experimentally measured synaptic behaviors.

Organic/inorganic hybrid synaptic transistors gated by proton conducting methylcellulose films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Chang Jin; Wan, Qing, E-mail: wanqing@nju.edu.cn, E-mail: yshi@nju.edu.cn; Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201

The idea of building a brain-inspired cognitive system has been around for several decades. Recently, electric-double-layer transistors gated by ion conducting electrolytes were reported as the promising candidates for synaptic electronics and neuromorphic system. In this letter, indium-zinc-oxide transistors gated by proton conducting methylcellulose electrolyte films were experimentally demonstrated with synaptic plasticity including paired-pulse facilitation and spatiotemporal-correlated dynamic logic. More importantly, a model based on proton-related electric-double-layer modulation and stretched-exponential decay function was proposed, and the theoretical results are in good agreement with the experimentally measured synaptic behaviors.

Improving the resolution in proton-detected through-space heteronuclear multiple quantum correlation NMR spectroscopy.

PubMed

Shen, Ming; Trébosc, J; Lafon, O; Pourpoint, F; Hu, Bingwen; Chen, Qun; Amoureux, J-P

2014-08-01

Connectivities and proximities between protons and low-gamma nuclei can be probed in solid-state NMR spectroscopy using two-dimensional (2D) proton-detected heteronuclear correlation, through Heteronuclear Multiple Quantum Correlation (HMQC) pulse sequence. The indirect detection via protons dramatically enhances the sensitivity. However, the spectra are often broadened along the indirect F1 dimension by the decay of heteronuclear multiple-quantum coherences under the strong (1)H-(1)H dipolar couplings. This work presents a systematic comparison of the performances of various decoupling schemes during the indirect t1 evolution period of dipolar-mediated HMQC (D-HMQC) experiment. We demonstrate that (1)H-(1)H dipolar decoupling sequences during t1, such as symmetry-based schemes, phase-modulated Lee-Goldburg (PMLG) and Decoupling Using Mind-Boggling Optimization (DUMBO), provide better resolution than continuous wave (1)H irradiation. We also report that high resolution requires the preservation of (1)H isotropic chemical shifts during the decoupling sequences. When observing indirectly broad spectra presenting numerous spinning sidebands, the D-HMQC sequence must be fully rotor-synchronized owing to the rotor-synchronized indirect sampling and dipolar recoupling sequence employed. In this case, we propose a solution to reduce artefact sidebands caused by the modulation of window delays before and after the decoupling application during the t1 period. Moreover, we show that (1)H-(1)H dipolar decoupling sequence using Smooth Amplitude Modulation (SAM) minimizes the t1-noise. The performances of the various decoupling schemes are assessed via numerical simulations and compared to 2D (1)H-{(13)C} D-HMQC experiments on [U-(13)C]-L-histidine⋅HCl⋅H2O at various magnetic fields and Magic Angle spinning (MAS) frequencies. Great resolution and sensitivity enhancements resulting from decoupling during t1 period enable the detection of heteronuclear correlation between aliphatic protons and ammonium (14)N sites in L-histidine⋅HCl⋅H2O. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

SU-FF-T-668: A Simple Algorithm for Range Modulation Wheel Design in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, X; Nazaryan, Vahagn; Gueye, Paul

2009-06-01

Purpose: To develop a simple algorithm in designing the range modulation wheel to generate a very smooth Spread-Out Bragg peak (SOBP) for proton therapy.Method and Materials: A simple algorithm has been developed to generate the weight factors in corresponding pristine Bragg peaks which composed a smooth SOBP in proton therapy. We used a modified analytical Bragg peak function based on Monte Carol simulation tool-kits of Geant4 as pristine Bragg peaks input in our algorithm. A simple METLAB(R) Quad Program was introduced to optimize the cost function in our algorithm. Results: We found out that the existed analytical function of Braggmore » peak can't directly use as pristine Bragg peak dose-depth profile input file in optimization of the weight factors since this model didn't take into account of the scattering factors introducing from the range shifts in modifying the proton beam energies. We have done Geant4 simulations for proton energy of 63.4 MeV with a 1.08 cm SOBP for variation of pristine Bragg peaks which composed this SOBP and modified the existed analytical Bragg peak functions for their peak heights, ranges of R{sub 0}, and Gaussian energies {sigma}{sub E}. We found out that 19 pristine Bragg peaks are enough to achieve a flatness of 1.5% of SOBP which is the best flatness in the publications. Conclusion: This work develops a simple algorithm to generate the weight factors which is used to design a range modulation wheel to generate a smooth SOBP in protonradiation therapy. We have found out that a medium number of pristine Bragg peaks are enough to generate a SOBP with flatness less than 2%. It is potential to generate data base to store in the treatment plan to produce a clinic acceptable SOBP by using our simple algorithm.« less

Cationic Covalent Organic Frameworks: A Simple Platform of Anionic Exchange for Porosity Tuning and Proton Conduction.

PubMed

Ma, Heping; Liu, Bailing; Li, Bin; Zhang, Liming; Li, Yang-Guang; Tan, Hua-Qiao; Zang, Hong-Ying; Zhu, Guangshan

2016-05-11

Mimicking proton conduction mechanism of Nafion to construct novel proton-conducting materials with low cost and high proton conductivity is of wide interest. Herein, we have designed and synthesized a cationic covalent organic framework with high thermal and chemical stability by combining a cationic monomer, ethidium bromide (EB) (3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide), with 1,3,5-triformylphloroglucinol (TFP) in Schiff base reactions. This is the first time that the stable cationic crystalline frameworks allowed for the fabrication of a series of charged COFs (EB-COF:X, X = F, Cl, Br, I) through ion exchange processes. Exchange of the extra framework ions can finely modulate the COFs' porosity and pore sizes at nanoscale. More importantly, by introducing PW12O40(3-) into this porous cationic framework, we can greatly enhance the proton conductivity of ionic COF-based material. To the best of our knowledge, EB-COF:PW12 shows the best proton conductivity at room temperature among ever reported porous organic materials.

Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

PubMed

Weber, Damien C; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escudé, Lluis; Caro, Monica; Pötter, Richard; Goitein, Gudrun; Lomax, Antony J; Miralbell, Raymond

2005-10-01

A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.

Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochrome c oxidase.

PubMed

Goyal, Puja; Lu, Jianxun; Yang, Shuo; Gunner, M R; Cui, Qiang

2013-11-19

Cytochrome c oxidase contributes to the transmembrane proton gradient by removing two protons from the high-pH side of the membrane each time the binuclear center active site is reduced. One proton goes to the binuclear center, whereas the other is pumped to the low-pH periplasmic space. Glutamate 286 (Glu286) has been proposed to serve as a transiently deprotonated proton donor. Using unrestrained atomistic molecular dynamics simulations, we show that the size of and water distribution in the hydrophobic cavity that holds Glu286 is controlled by the protonation state of the propionic acid of heme a3, a group on the proton outlet pathway. Protonation of the propionate disrupts hydrogen bonding to two side chains, allowing a loop to swing open. Continuum electrostatics and atomistic free-energy perturbation calculations show that the resultant changes in hydration and electrostatic interactions lower the Glu proton affinity by at least 5 kcal/mol. These changes in the internal hydration level occur in the absence of major conformational transitions and serve to stabilize needed transient intermediates in proton transport. The trigger is not the protonation of the Glu of interest, but rather the protonation of a residue ∼10 Å away. Thus, unlike local water penetration to stabilize a new charge, this finding represents a specific role for water molecules in the protein interior, mediating proton transfers and facilitating ion transport.

Determination of the depth dose distribution of proton beam using PRESAGE TM dosimeter

NASA Astrophysics Data System (ADS)

Zhao, L.; Das, I. J.; Zhao, Q.; Thomas, A.; Adamovics, J.; Oldman, M.

2010-11-01

PRESAGETM dosimeter dosimeter has been proved useful for 3D dosimetry in conventional photon therapy and IMRT [1-5]. Our objective is to examine the use of PRESAGETM dosimeter for verification of depth dose distribution in proton beam therapy. Three PRESAGETM samples were irradiated with a 79 MeV un-modulated proton beam. Percent depth dose profile measured from the PRESAGETM dosimeter is compared with data obtained in a water phantom using a parallel plate Advanced Markus chamber. The Bragg-peak position determined from the PRESAGETM is within 2 mm compared to measurements in water. PRESAGETM shows a highly linear response to proton dose. However, PRESAGETM also reveals an underdosage around the Bragg peak position due to LET effects. Depth scaling factor and quenching correction factor need further investigation. Our initial result shows that PRESAGETM has promising dosimetric characteristics that could be suitable for proton beam dosimetry.

Splash albedo protons between 4 and 315 MeV at high and low geomagnetic latitudes

NASA Technical Reports Server (NTRS)

Wenzel, K.-P.; Stone, E. C.; Vogt, R. E.

1975-01-01

Results are reported for measurements of the differential energy spectrum of splash-albedo protons at high geomagnetic latitude during three periods of the last solar cycle as well as at low latitude during one of those periods. The measurements were made with a balloon-borne solid-state detector telescope. Splash-albedo protons with energies between 4 and 315 MeV were observed in fluxes of approximately 81, 70, and 48 protons/sq m per sec per sr at high latitude and in fluxes of approximately 37 protons/sq m per sec per sr at low latitude. It is shown that the difference between the first and third high-latitude measurements was due to solar modulation of the cosmic-ray parent nuclei. The albedo spectrum is found to have a similar shape for both latitudes, and it is suggested that the difference in intensity can be explained by different local geomagnetic cutoffs.

Single-energy intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

2015-09-01

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described. The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods. It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan. When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

Single-energy intensity modulated proton therapy.

PubMed

Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

2015-10-07

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

Proton Pump Inhibition Increases Rapid Eye Movement Sleep in the Rat

PubMed Central

Jha, Sushil K.

2014-01-01

Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor “lansoprazole” on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg) were injected intraperitoneally in the same animal (n = 7) and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was 9.26 ± 1.03 and 9.09 ± 0.54, respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle) and 34.21% (from low dose). Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker “amiloride” (10 mg/kg; i.p.) (n = 5) did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep. PMID:24701564

Proton mediated control of biochemical reactions with bioelectronic pH modulation

NASA Astrophysics Data System (ADS)

Deng, Yingxin; Miyake, Takeo; Keene, Scott; Josberger, Erik E.; Rolandi, Marco

2016-04-01

In Nature, protons (H+) can mediate metabolic process through enzymatic reactions. Examples include glucose oxidation with glucose dehydrogenase to regulate blood glucose level, alcohol dissolution into carboxylic acid through alcohol dehydrogenase, and voltage-regulated H+ channels activating bioluminescence in firefly and jellyfish. Artificial devices that control H+ currents and H+ concentration (pH) are able to actively influence biochemical processes. Here, we demonstrate a biotransducer that monitors and actively regulates pH-responsive enzymatic reactions by monitoring and controlling the flow of H+ between PdHx contacts and solution. The present transducer records bistable pH modulation from an “enzymatic flip-flop” circuit that comprises glucose dehydrogenase and alcohol dehydrogenase. The transducer also controls bioluminescence from firefly luciferase by affecting solution pH.

Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

PubMed

Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

2017-05-01

Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

Polymorphism and Modulation of Para-Substituted l-Phenylalanine.

PubMed

Sögütoglu, Leyla-Cann; Lutz, Martin; Meekes, Hugo; de Gelder, René; Vlieg, Elias

2017-12-06

The crystal structure of para -methyl-l-phenylalanine at 230 K resembles that of the para-fluorinated analogue from the literature but is commensurately modulated with seven molecules in the asymmetric unit ( Z ' = 7). At 100 K, the superstructure loses its modulation, leading to a unit cell with Z ' = 1, with clear disorder in the phenyl ring orientations. The methyl-substituent in para -methyl-l-phenylalanine has, in contrast to fluorine, no polar interactions with protons of neighboring molecules, which might allow for the well-defined modulation of the crystal structure at 230 K.

Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein.

PubMed

Tao, Shi-Cong; Gao, You-Shui; Zhu, Hong-Yi; Yin, Jun-Hui; Chen, Yi-Xuan; Zhang, Yue-Lei; Guo, Shang-Chun; Zhang, Chang-Qing

2016-06-03

The pH of extracellular fluids is a basic property of the tissue microenvironment and is normally maintained at 7.40 ± 0.05 in humans. Many pathological circumstances, such as ischemia, inflammation, and tumorigenesis, result in the reduction of extracellular pH in the affected tissues. In this study, we reported that the osteogenic differentiation of BMSCs was significantly inhibited by decreases in the extracellular pH. Moreover, we demonstrated that proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. Additionally, we found that YAP was the downstream effector of GPR4 signaling. Our findings revealed that the extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway.

The technical implementation of an IMPT system for research purpose

NASA Astrophysics Data System (ADS)

Nguyen, T. T. C.; Nguyen, B. T.; Mai, N. V.

2018-03-01

Because of their superior distribution, proton beams is the state-of-the-art modality in radiation therapy. There is a variety of researchers about proton therapy to utilize it. In this paper, we introduce a Matlab-based platform to develop and prototype proton treatment planning using LAP and CERR. Planning workflow to make an IMPT plan is described in details and demonstrated by a prostate case. The results showed that most of the dose criteria are satisfied, except for bladder and rectum, 2% of the volume of each organ receiving the least dose of 77.5 Gy (RBE) instead of 76 Gy(RBE) as dose requirements suggested by ICRU 78. As a result, planners absolutely can implement Intensity Modulated Proton Therapy plans by LAP and CERR for research purpose.

Development and application of a water calorimeter for the absolute dosimetry of short-range particle beams.

PubMed

Renaud, J; Rossomme, S; Sarfehnia, A; Vynckier, S; Palmans, H; Kacperek, A; Seuntjens, J

2016-09-21

In this work, we describe a new design of water calorimeter built to measure absorbed dose in non-standard radiation fields with reference depths in the range of 6-20 mm, and its initial testing in clinical electron and proton beams. A functioning calorimeter prototype with a total water equivalent thickness of less than 30 mm was constructed in-house and used to obtain measurements in clinical accelerator-based 6 MeV and 8 MeV electron beams and cyclotron-based 60 MeV monoenergetic and modulated proton beams. Corrections for the conductive heat transfer due to dose gradients and non-water materials was also accounted for using a commercial finite element method software package. Absorbed dose to water was measured with an associated type A standard uncertainty of approximately 0.4% and 0.2% for the electron and proton beam experiments, respectively. In terms of thermal stability, drifts were on the order of a couple of hundred µK min -1 , with a short-term variation of 5-10 µK. Heat transfer correction factors ranged between 1.021 and 1.049. The overall combined standard uncertainty on the absorbed dose to water was estimated to be 0.6% for the 6 MeV and 8 MeV electron beams, as well as for the 60 MeV monoenergetic protons, and 0.7% for the modulated 60 MeV proton beam. This study establishes the feasibility of developing an absorbed dose transfer standard for short-range clinical electrons and protons and forms the basis for a transportable dose standard for direct calibration of ionization chambers in the user's beam. The largest contributions to the combined standard uncertainty were the positioning (⩽0.5%) and the correction due to conductive heat transfer (⩽0.4%). This is the first time that water calorimetry has been used in such a low energy proton beam.

Development and application of a water calorimeter for the absolute dosimetry of short-range particle beams

NASA Astrophysics Data System (ADS)

Renaud, J.; Rossomme, S.; Sarfehnia, A.; Vynckier, S.; Palmans, H.; Kacperek, A.; Seuntjens, J.

2016-09-01

In this work, we describe a new design of water calorimeter built to measure absorbed dose in non-standard radiation fields with reference depths in the range of 6-20 mm, and its initial testing in clinical electron and proton beams. A functioning calorimeter prototype with a total water equivalent thickness of less than 30 mm was constructed in-house and used to obtain measurements in clinical accelerator-based 6 MeV and 8 MeV electron beams and cyclotron-based 60 MeV monoenergetic and modulated proton beams. Corrections for the conductive heat transfer due to dose gradients and non-water materials was also accounted for using a commercial finite element method software package. Absorbed dose to water was measured with an associated type A standard uncertainty of approximately 0.4% and 0.2% for the electron and proton beam experiments, respectively. In terms of thermal stability, drifts were on the order of a couple of hundred µK min-1, with a short-term variation of 5-10 µK. Heat transfer correction factors ranged between 1.021 and 1.049. The overall combined standard uncertainty on the absorbed dose to water was estimated to be 0.6% for the 6 MeV and 8 MeV electron beams, as well as for the 60 MeV monoenergetic protons, and 0.7% for the modulated 60 MeV proton beam. This study establishes the feasibility of developing an absorbed dose transfer standard for short-range clinical electrons and protons and forms the basis for a transportable dose standard for direct calibration of ionization chambers in the user’s beam. The largest contributions to the combined standard uncertainty were the positioning (⩽0.5%) and the correction due to conductive heat transfer (⩽0.4%). This is the first time that water calorimetry has been used in such a low energy proton beam.

An evaluation of spatial resolution of a prototype proton CT scanner.

PubMed

Plautz, Tia E; Bashkirov, V; Giacometti, V; Hurley, R F; Johnson, R P; Piersimoni, P; Sadrozinski, H F-W; Schulte, R W; Zatserklyaniy, A

2016-12-01

To evaluate the spatial resolution of proton CT using both a prototype proton CT scanner and Monte Carlo simulations. A custom cylindrical edge phantom containing twelve tissue-equivalent inserts with four different compositions at varying radial displacements from the axis of rotation was developed for measuring the modulation transfer function (MTF) of a prototype proton CT scanner. Two scans of the phantom, centered on the axis of rotation, were obtained with a 200 MeV, low-intensity proton beam: one scan with steps of 4°, and one scan with the phantom continuously rotating. In addition, Monte Carlo simulations of the phantom scan were performed using scanners idealized to various degrees. The data were reconstructed using an iterative projection method with added total variation superiorization based on individual proton histories. Edge spread functions in the radial and azimuthal directions were obtained using the oversampling technique. These were then used to obtain the modulation transfer functions. The spatial resolution was defined by the 10% value of the modulation transfer function (MTF 10% ) in units of line pairs per centimeter (lp/cm). Data from the simulations were used to better understand the contributions of multiple Coulomb scattering in the phantom and the scanner hardware, as well as the effect of discretization of proton location. The radial spatial resolution of the prototype proton CT scanner depends on the total path length, W, of the proton in the phantom, whereas the azimuthal spatial resolution depends both on W and the position, u - , at which the most-likely path uncertainty is evaluated along the path. For protons contributing to radial spatial resolution, W varies with the radial position of the edge, whereas for protons contributing to azimuthal spatial resolution, W is approximately constant. For a pixel size of 0.625 mm, the radial spatial resolution of the image reconstructed from the fully idealized simulation data ranged between 6.31 ± 0.36 lp/cm for W = 197 mm i.e., close to the center of the phantom, and 13.79 ± 0.36 lp/cm for W = 97 mm, near the periphery of the phantom. The azimuthal spatial resolution ranged from 6.99 ± 0.23 lp/cm at u - = 75 mm (near the center) to 11.20 ± 0.26 lp/cm at u - = 20 mm (near the periphery). Multiple Coulomb scattering limits the radial spatial resolution for path lengths greater than approximately 130 mm, and the azimuthal spatial resolution for positions of evaluation greater than approximately 40 mm for W = 199 mm. The radial spatial resolution of the image reconstructed from data from the 4° stepped experimental scan ranged from 5.11 ± 0.61 lp/cm for W = 197 mm to 8.58 ± 0.50 lp/cm for W = 97 mm. In the azimuthal direction, the spatial resolution ranged from 5.37 ± 0.40 lp/cm at u - = 75 mm to 7.27 ± 0.39 lp/cm at u - = 20 mm. The continuous scan achieved the same spatial resolution as that of the stepped scan. Multiple Coulomb scattering in the phantom is the limiting physical factor of the achievable spatial resolution of proton CT; additional loss of spatial resolution in the prototype system is associated with scattering in the proton tracking system and inadequacies of the proton path estimate used in the iterative reconstruction algorithm. Improvement in spatial resolution may be achievable by improving the most likely path estimate by incorporating information about high and low density materials, and by minimizing multiple Coulomb scattering in the proton tracking system.

An evaluation of spatial resolution of a prototype proton CT scanner

PubMed Central

Plautz, Tia E.; Bashkirov, V.; Giacometti, V.; Hurley, R. F.; Piersimoni, P.; Sadrozinski, H. F.-W.; Schulte, R. W.; Zatserklyaniy, A.

2016-01-01

Purpose: To evaluate the spatial resolution of proton CT using both a prototype proton CT scanner and Monte Carlo simulations. Methods: A custom cylindrical edge phantom containing twelve tissue-equivalent inserts with four different compositions at varying radial displacements from the axis of rotation was developed for measuring the modulation transfer function (MTF) of a prototype proton CT scanner. Two scans of the phantom, centered on the axis of rotation, were obtained with a 200 MeV, low-intensity proton beam: one scan with steps of 4°, and one scan with the phantom continuously rotating. In addition, Monte Carlo simulations of the phantom scan were performed using scanners idealized to various degrees. The data were reconstructed using an iterative projection method with added total variation superiorization based on individual proton histories. Edge spread functions in the radial and azimuthal directions were obtained using the oversampling technique. These were then used to obtain the modulation transfer functions. The spatial resolution was defined by the 10% value of the modulation transfer function (MTF10%) in units of line pairs per centimeter (lp/cm). Data from the simulations were used to better understand the contributions of multiple Coulomb scattering in the phantom and the scanner hardware, as well as the effect of discretization of proton location. Results: The radial spatial resolution of the prototype proton CT scanner depends on the total path length, W, of the proton in the phantom, whereas the azimuthal spatial resolution depends both on W and the position, u−, at which the most-likely path uncertainty is evaluated along the path. For protons contributing to radial spatial resolution, W varies with the radial position of the edge, whereas for protons contributing to azimuthal spatial resolution, W is approximately constant. For a pixel size of 0.625 mm, the radial spatial resolution of the image reconstructed from the fully idealized simulation data ranged between 6.31 ± 0.36 lp/cm for W = 197 mm i.e., close to the center of the phantom, and 13.79 ± 0.36 lp/cm for W = 97 mm, near the periphery of the phantom. The azimuthal spatial resolution ranged from 6.99 ± 0.23 lp/cm at u− = 75 mm (near the center) to 11.20 ± 0.26 lp/cm at u− = 20 mm (near the periphery). Multiple Coulomb scattering limits the radial spatial resolution for path lengths greater than approximately 130 mm, and the azimuthal spatial resolution for positions of evaluation greater than approximately 40 mm for W = 199 mm. The radial spatial resolution of the image reconstructed from data from the 4° stepped experimental scan ranged from 5.11 ± 0.61 lp/cm for W = 197 mm to 8.58 ± 0.50 lp/cm for W = 97 mm. In the azimuthal direction, the spatial resolution ranged from 5.37 ± 0.40 lp/cm at u− = 75 mm to 7.27 ± 0.39 lp/cm at u− = 20 mm. The continuous scan achieved the same spatial resolution as that of the stepped scan. Conclusions: Multiple Coulomb scattering in the phantom is the limiting physical factor of the achievable spatial resolution of proton CT; additional loss of spatial resolution in the prototype system is associated with scattering in the proton tracking system and inadequacies of the proton path estimate used in the iterative reconstruction algorithm. Improvement in spatial resolution may be achievable by improving the most likely path estimate by incorporating information about high and low density materials, and by minimizing multiple Coulomb scattering in the proton tracking system. PMID:27908179

3D printed plastics for beam modulation in proton therapy

NASA Astrophysics Data System (ADS)

Lindsay, C.; Kumlin, J.; Jirasek, A.; Lee, R.; Martinez, D. M.; Schaffer, P.; Hoehr, C.

2015-06-01

Two 3D printing methods, fused filament fabrication (FFF) and PolyJet™ (PJ) were investigated for suitability in clinical proton therapy (PT) energy modulation. Measurements of printing precision, printed density and mean stopping power are presented. FFF is found to be accurate to 0.1 mm, to contain a void fraction of 13% due to air pockets and to have a mean stopping power dependent on geometry. PJ was found to print accurate to 0.05 mm, with a material density and mean stopping power consistent with solid poly(methyl methacrylate) (PMMA). Both FFF and PJ were found to print significant, sporadic defects associated with sharp edges on the order of 0.2 mm. Site standard PT modulator wheels were printed using both methods. Measured depth-dose profiles with a 74 MeV beam show poor agreement between PMMA and printed FFF wheels. PJ printed wheel depth-dose agreed with PMMA within 1% of treatment dose except for a distal falloff discrepancy of 0.5 mm.

Modulation of Active Site Electronic Structure by the Protein Matrix to Control [NiFe] Hydrogenase Reactivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Dayle MA; Raugei, Simone; Squier, Thomas C.

2014-09-30

Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni–Fe cluster in the catalytically active Ni-C state. There aremore » correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.« less

Modulation of active site electronic structure by the protein matrix to control [NiFe] hydrogenase reactivity.

PubMed

Smith, Dayle M A; Raugei, Simone; Squier, Thomas C

2014-11-21

Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni-Fe cluster in the catalytically active Ni-C state. There are correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.

Zinc chelation with hydroxamate in histone deacetylases modulated by water access to the linker binding channel.

PubMed

Wu, Ruibo; Lu, Zhenyu; Cao, Zexing; Zhang, Yingkai

2011-04-27

It is of significant biological interest and medical importance to develop class- and isoform-selective histone deacetylase (HDAC) modulators. The impact of the linker component on HDAC inhibition specificity has been revealed but is not understood. Using Born-Oppenheimer ab initio QM/MM MD simulations, a state-of-the-art approach to simulating metallo-enzymes, we have found that the hydroxamic acid remains to be protonated upon its binding to HDAC8, and thus disproved the mechanistic hypothesis that the distinct zinc-hydroxamate chelation modes between two HDAC subclasses come from different protonation states of the hydroxamic acid. Instead, our simulations suggest a novel mechanism in which the chelation mode of hydroxamate with the zinc ion in HDACs is modulated by water access to the linker binding channel. This new insight into the interplay between the linker binding and the zinc chelation emphasizes its importance and gives guidance regarding linker design for the development of new class-IIa-specific HDAC inhibitors.

Proton-beam writing channel based on an electrostatic accelerator

NASA Astrophysics Data System (ADS)

Lapin, A. S.; Rebrov, V. A.; Kolin'ko, S. V.; Salivon, V. F.; Ponomarev, A. G.

2016-09-01

We have described the structure of the proton-beam writing channel as a continuation of a nuclear scanning microprobe channel. The problem of the accuracy of positioning a probe by constructing a new high-frequency electrostatic scanning system has been solved. Special attention has been paid to designing the probe-forming system and its various configurations have been considered. The probe-forming system that best corresponds to the conditions of the lithographic process has been found based on solving the problem of optimizing proton beam formation. A system for controlling beam scanning using multifunctional module of integrated programmable logic systems has been developed.

Reevaluation of spin-dependent WIMP-proton interactions as an explanation of the DAMA data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nobile, Eugenio Del; Gelmini, Graciela B.; Georgescu, Andreea

2015-08-25

We reexamine the interpretation of the annual modulation signal observed by the DAMA experiment as due to WIMPs with a spin-dependent coupling mostly to protons. We consider both axial-vector and pseudo-scalar couplings, and elastic as well as endothermic and exothermic inelastic scattering. We conclude that the DAMA signal is in strong tension with null results of other direct detection experiments, particularly PICASSO and KIMS.

Photons, protons or carbon ions for stage I non-small cell lung cancer - Results of the multicentric ROCOCO in silico study.

PubMed

Wink, Krista C J; Roelofs, Erik; Simone, Charles B; Dechambre, David; Santiago, Alina; van der Stoep, Judith; Dries, Wim; Smits, Julia; Avery, Stephen; Ammazzalorso, Filippo; Jansen, Nicolas; Jelen, Urszula; Solberg, Timothy; de Ruysscher, Dirk; Troost, Esther G C

2018-03-12

To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial. For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions. The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ. On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient. Copyright © 2018 Elsevier B.V. All rights reserved.

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO4 crystals

NASA Astrophysics Data System (ADS)

Adams, T.; Adzic, P.; Ahuja, S.; Anderson, D.; Andrews, M. B.; Antropov, I.; Antunovic, Z.; Arcidiacono, R.; Arenton, M. W.; Argirò, S.; Askew, A.; Attikis, A.; Auffray, E.; Baccaro, S.; Baffioni, S.; Bailleux, D.; Baillon, P.; Barney, D.; Barone, L.; Bartoloni, A.; Bartosik, N.; Becheva, E.; Bein, S.; Silva, C. Beirāo Da Cruz E.; Bell, K. W.; Benaglia, A.; Bendavid, J.; Berry, D.; Besancon, M.; Betev, B.; Bialas, W.; Bianchini, L.; Biino, C.; Bitioukov, S.; Bornheim, A.; Brianza, L.; Brinkerhoff, A.; Brown, R. M.; Brummitt, A.; Busson, P.; Candelise, V.; Carrillo Montoya, C. A.; Cartiglia, N.; Cavallari, F.; Chang, Y. W.; Chen, K. F.; Chevenier, G.; Chipaux, R.; Clement, E.; Cockerill, D. J. A.; Corpe, L.; Couderc, F.; Courbon, B.; Cox, B.; Cucciati, G.; Cussans, D.; D'imperio, G.; Da Silva Di Calafiori, D. R.; Dafinei, I.; Daguin, J.; Daskalakis, G.; Tinoco Mendes, A. D.; De Guio, F.; Degano, A.; Dejardin, M.; Del Re, D.; Della Ricca, G.; Denegri, D.; Depasse, P.; Dev, N.; Deyrail, D.; Di Marco, E.; Diamond, B.; Diemoz, M.; Dissertori, G.; Dittmar, M.; Djambazov, L.; Doan, T. H.; Dobrzynski, L.; Dolgopolov, A.; Donegà, M.; Dordevic, M.; Dröge, M.; Durkin, T.; Dutta, D.; El Mamouni, H.; Elliott-Peisert, A.; Elmalis, E.; Fabbro, B.; Fasanella, G.; Faure, J.; Fay, J.; Fedorov, A.; Ferri, F.; Francis, B.; Frank, N.; Franzoni, G.; Funk, W.; Ganjour, S.; Gascon, S.; Gastal, M.; Geerebaert, Y.; Gelli, S.; Gerosa, R.; Ghezzi, A.; Giakoumopoulou, V. A.; Givernaud, A.; Gninenko, S.; Godinovic, N.; Goeckner-Wald, N.; Golubev, N.; Govoni, P.; Gras, P.; Guilloux, F.; Haller, C.; Hamel de Monchenault, G.; Hansen, M.; Hansen, P.; Hardenbrook, J.; Heath, H. F.; Hill, J.; Hirosky, R.; Hobson, P. R.; Holme, O.; Honma, A.; Hou, W.-S.; Hsiung, Y.; Iiyama, Y.; Ille, B.; Ingram, Q.; Jain, S.; Jarry, P.; Jessop, C.; Jovanovic, D.; Kachanov, V.; Kalafut, S.; Kao, K. Y.; Kellams, N.; Kesisoglou, S.; Khatiwada, A.; Konoplyannikov, A.; Konstantinov, D.; Korzhik, M.; Kovac, M.; Kubota, Y.; Kucher, I.; Kumar, A.; Kumar, A.; Kuo, C.; Kyberd, P.; Kyriakis, A.; Latyshev, G.; Lecoq, P.; Ledovskoy, A.; Lei, Y. J.; Lelas, D.; Lethuillier, M.; Li, H.; Lin, W.; Liu, Y. F.; Locci, E.; Longo, E.; Loukas, D.; Lu, R.-S.; Lucchini, M. T.; Lustermann, W.; Mackay, C. K.; Magniette, F.; Malcles, J.; Malhotra, S.; Mandjavidze, I.; Maravin, Y.; Margaroli, F.; Marinelli, N.; Marini, A. C.; Martelli, A.; Marzocchi, B.; Massironi, A.; Matveev, V.; Mechinsky, V.; Meng, F.; Meridiani, P.; Micheli, F.; Milosevic, J.; Mousa, J.; Musella, P.; Nessi-Tedaldi, F.; Neu, C.; Newman, H.; Nicolaou, C.; Nourbakhsh, S.; Obertino, M. M.; Organtini, G.; Orimoto, T.; Paganini, P.; Paganis, E.; Paganoni, M.; Pandolfi, F.; Panov, V.; Paramatti, R.; Parracho, P.; Pastrone, N.; Paulini, M.; Pauss, F.; Pauwels, K.; Pellegrino, F.; Pena, C.; Perniè, L.; Peruzzi, M.; Petrakou, E.; Petyt, D.; Pigazzini, S.; Piroué, P.; Planer, M.; Plestina, R.; Polic, D.; Prosper, H.; Ptochos, F.; Puljak, I.; Quittnat, M.; Ragazzi, S.; Rahatlou, S.; Rander, J.; Ranjan, K.; Rasteiro Da Silva, J.; Razis, P. A.; Romanteau, T.; Rosowsky, A.; Rovelli, C.; Rusack, R.; Salerno, R.; Santanastasio, F.; Santra, A.; Schönenberger, M.; Seez, C.; Sharma, V.; Shepherd-Themistocleous, C.; Shiu, J. G.; Shivpuri, R. K.; Singovsky, A.; Sinthuprasith, T.; Sirois, Y.; Smiljkovic, N.; Soffi, L.; Sun, M.; Symonds, P.; Tabarelli de Fatis, T.; Tambe, N.; Tarasov, I.; Taroni, S.; Teixeira De Lima, R.; Thea, A.; Theofilatos, K.; Thiant, F.; Titov, M.; Torbet, M.; Trapani, P. P.; Tropea, P.; Tsai, J. f.; Tsirou, A.; Turkewitz, J.; Tyurin, N.; Tzeng, Y. M.; Uzunian, A.; Valls, N.; Varela, J.; Veeraraghavan, V.; Verdini, P. G.; Vichoudis, P.; Vlassov, E.; Wang, J.; Wang, T.; Weinberg, M.; Wolfe, E.; Wood, J.; Zabi, A.; Zahid, S.; Zelepoukine, S.; Zghiche, A.; Zhang, L.; Zhu, K.; Zhu, R.; Zuyeuski, R.

2016-04-01

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1× 1013 and 1.3× 1014 cm-2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb-1 and 3000 fb-1 respectively, corresponding to the end of the LHC and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. The experimental results obtained can be used to estimate the long term performance of the CMS ECAL.

Is it necessary to plan with safety margins for actively scanned proton therapy?

NASA Astrophysics Data System (ADS)

Albertini, F.; Hug, E. B.; Lomax, A. J.

2011-07-01

In radiation therapy, a plan is robust if the calculated and the delivered dose are in agreement, even in the case of different uncertainties. The current practice is to use safety margins, expanding the clinical target volume sufficiently enough to account for treatment uncertainties. This, however, might not be ideal for proton therapy and in particular when using intensity modulated proton therapy (IMPT) plans as degradation in the dose conformity could also be found in the middle of the target resulting from misalignments of highly in-field dose gradients. Single field uniform dose (SFUD) and IMPT plans have been calculated for different anatomical sites and the need for margins has been assessed by analyzing plan robustness to set-up and range uncertainties. We found that the use of safety margins is a good way to improve plan robustness for SFUD and IMPT plans with low in-field dose gradients but not necessarily for highly modulated IMPT plans for which only a marginal improvement in plan robustness could be detected through the definition of a planning target volume.

WE-D-17A-06: Optically Stimulated Luminescence Detectors as ‘LET-Meters’ in Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Granville, D; Sahoo, N; Sawakuchi, GO

Purpose: To demonstrate and evaluate the potential of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of linear energy transfer (LET) in therapeutic proton beams. Methods: Batches of Al2O2:C OSLDs were irradiated with an absorbed dose of 0.2 Gy in un-modulated proton beams of varying LET (0.67 keV/μm to 2.58 keV/μm). The OSLDs were read using continuous wave (CW-OSL) and pulsed (P-OSL) stimulation modes. We parameterized and calibrated three characteristics of the OSL signals as functions of LET: CW-OSL curve shape, P-OSL curve shape and the ratio of the two OSL emission band intensities (ultraviolet/blue ratio). Calibration curves were createdmore » for each of these characteristics to describe their behaviors as functions of LET. The true LET values were determined using a validated Monte Carlo model of the proton therapy nozzle used to irradiate the OSLDs. We then irradiated batches of OSLDs with an absorbed dose of 0.2 Gy at various depths in two modulated proton beams (140 MeV, 4 cm wide spread-out Bragg peak (SOBP) and 250 MeV, 10 cm wide SOBP). The LET values were calculated using the OSL response and the calibration curves. Finally, measured LET values were compared to the true values determined using Monte Carlo simulations. Results: The CW-OSL curve shape, P-OSL curve shape and the ultraviolet/blue-ratio provided proton LET estimates within 12.4%, 5.7% and 30.9% of the true values, respectively. Conclusion: We have demonstrated that LET can be measured within 5.7% using Al2O3:C OSLDs in the therapeutic proton beams used in this investigation. From a single OSLD readout, it is possible to measure both the absorbed dose and LET. This has potential future applications in proton therapy quality assurance, particularly for treatment plans based on optimization of LET distributions. This research was partially supported by the Natural Sciences and Engineering Research Council of Canada.« less

Analog signal pre-processing for the Fermilab Main Injector BPM upgrade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saewert, A.L.; Rapisarda, S.M.; Wendt, M.

2006-05-01

An analog signal pre-processing scheme was developed, in the framework of the Fermilab Main Injector Beam Position Monitor (BPM) Upgrade, to interface BPM pickup signals to the new digital receiver based read-out system. A key component is the 8-channel electronics module, which uses separate frequency selective gain stages to acquire 53 MHz bunched proton, and 2.5 MHz anti-proton signals. Related hardware includes a filter and combiner box to sum pickup electrode signals in the tunnel. A controller module allows local/remote control of gain settings and activation of gain stages, and supplies test signals. Theory of operation, system overview, and somemore » design details are presented, as well as first beam measurements of the prototype hardware.« less

In situ Observations of Magnetosonic Waves Modulated by Background Plasma Density

NASA Astrophysics Data System (ADS)

Yu, X.; Yuan, Z.; Huang, S.; Wang, D.; Funsten, H. O.

2017-12-01

We report in situ observations by the Van Allen Probe mission that magnetosonic (MS) waves are clearly relevant to appear relevant to the background plasma number density. As the satellite moved across dense and tenuous plasma alternatively, MS waves occurred only in lower density region. As the observed protons with 'ring' distributions provide free energy, local linear growth rates are calculated and show that magnetosonic waves can be locally excited in tenuous plasma. With variations of the background plasma density, the temporal variations of local wave growth rates calculated with the observed proton ring distributions, show a remarkable agreement with those of the observed wave amplitude. Therefore, the paper provides a direct proof that background plasma densities can modulate the amplitudes of magnetosonic waves through controlling the wave growth rates.

Proton mediated control of biochemical reactions with bioelectronic pH modulation

DOE PAGES

Deng, Yingxin; Miyake, Takeo; Keene, Scott; ...

2016-04-07

In Nature, protons (H +) can mediate metabolic process through enzymatic reactions. Examples include glucose oxidation with glucose dehydrogenase to regulate blood glucose level, alcohol dissolution into carboxylic acid through alcohol dehydrogenase, and voltage-regulated H + channels activating bioluminescence in firefly and jellyfish. Artificial devices that control H + currents and H + concentration (pH) are able to actively influence biochemical processes. Here, we demonstrate a biotransducer that monitors and actively regulates pH-responsive enzymatic reactions by monitoring and controlling the flow of H + between PdH x contacts and solution. The present transducer records bistable pH modulation from an “enzymaticmore » flip-flop” circuit that comprises glucose dehydrogenase and alcohol dehydrogenase. Furthermore, the transducer also controls bioluminescence from firefly luciferase by affecting solution pH.« less

Electrical-pulse-induced resistivity modulation in Pt/TiO2-δ/Pt multilayer device related to nanoionics-based neuromorphic function

NASA Astrophysics Data System (ADS)

Kawamura, Kinya; Tsuchiya, Takashi; Takayanagi, Makoto; Terabe, Kazuya; Higuchi, Tohru

2017-06-01

Resistivity modulation behavior in Pt/TiO2-δ/Pt multilayer devices was investigated in terms of nanoionics-based neuromorphic function. The current relaxation behavior, which corresponds to short-term and long-term memorization in neuromorphic function, was analyzed using electrical pulses. In contrast to the huge difference in ionic conductivity for bulk crystal materials of TiO2-δ and WO3, the difference in the relaxation behavior was small. Rutherford backscattering spectrometry and hydrogen forward scattering spectrometry revealed that the TiO2-δ thin film contained 5.6 at. % of protons. This indicates that the neuromorphic function in TiO2-δ-based devices is caused by extrinsic proton transport, presumably through the grain boundary.

Proton mediated control of biochemical reactions with bioelectronic pH modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Yingxin; Miyake, Takeo; Keene, Scott

In Nature, protons (H +) can mediate metabolic process through enzymatic reactions. Examples include glucose oxidation with glucose dehydrogenase to regulate blood glucose level, alcohol dissolution into carboxylic acid through alcohol dehydrogenase, and voltage-regulated H + channels activating bioluminescence in firefly and jellyfish. Artificial devices that control H + currents and H + concentration (pH) are able to actively influence biochemical processes. Here, we demonstrate a biotransducer that monitors and actively regulates pH-responsive enzymatic reactions by monitoring and controlling the flow of H + between PdH x contacts and solution. The present transducer records bistable pH modulation from an “enzymaticmore » flip-flop” circuit that comprises glucose dehydrogenase and alcohol dehydrogenase. Furthermore, the transducer also controls bioluminescence from firefly luciferase by affecting solution pH.« less

Cost of New Technologies in Prostate Cancer Treatment: Systematic Review of Costs and Cost Effectiveness of Robotic-assisted Laparoscopic Prostatectomy, Intensity-modulated Radiotherapy, and Proton Beam Therapy.

PubMed

Schroeck, Florian Rudolf; Jacobs, Bruce L; Bhayani, Sam B; Nguyen, Paul L; Penson, David; Hu, Jim

2017-11-01

Some of the high costs of robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and proton beam therapy may be offset by better outcomes or less resource use during the treatment episode. To systematically review the literature to identify the key economic trade-offs implicit in a particular treatment choice for prostate cancer. We systematically reviewed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and protocol. We searched Medline, Embase, and Web of Science for articles published between January 2001 and July 2016, which compared the treatment costs of RARP, IMRT, or proton beam therapy to the standard treatment. We identified 37, nine, and three studies, respectively. RARP is costlier than radical retropubic prostatectomy for hospitals and payers. However, RARP has the potential for a moderate cost advantage for payers and society over a longer time horizon when optimal cancer and quality-of-life outcomes are achieved. IMRT is more expensive from a payer's perspective compared with three-dimensional conformal radiotherapy, but also more cost effective when defined by an incremental cost effectiveness ratio <$50 000 per quality-adjusted life year. Proton beam therapy is costlier than IMRT and its cost effectiveness remains unclear given the limited comparative data on outcomes. Using the Grades of Recommendation, Assessment, Development and Evaluation approach, the quality of evidence was low for RARP and IMRT, and very low for proton beam therapy. Treatment with new versus traditional technologies is costlier. However, given the low quality of evidence and the inconsistencies across studies, the precise difference in costs remains unclear. Attempts to estimate whether this increased cost is worth the expense are hampered by the uncertainty surrounding improvements in outcomes, such as cancer control and side effects of treatment. If the new technologies can consistently achieve better outcomes, then they may be cost effective. We review the cost and cost effectiveness of robot-assisted radical prostatectomy, intensity-modulated radiotherapy, and proton beam therapy in prostate cancer treatment. These technologies are costlier than their traditional counterparts. It remains unclear whether their use is associated with improved cure and reduced morbidity, and whether the increased cost is worth the expense. Published by Elsevier B.V.

Observation of the Self-Modulation Instability via Time-Resolved Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, M.; Engel, J.; Good, J.

Self-modulation of an electron beam in a plasma has been observed. The propagation of a long (several plasma wavelengths) electron bunch in an overdense plasma resulted in the production of multiple bunches via the self-modulation instability. Using a combination of a radio-frequency deflector and a dipole spectrometer, the time and energy structure of the self-modulated beam was measured. The longitudinal phase space measurement showed the modulation of a long electron bunch into three bunches with an approximatelymore » $$200\\text{ }\\text{ }\\mathrm{keV}/c$$ amplitude momentum modulation. Demonstrating this effect is a breakthrough for proton-driven plasma accelerator schemes aiming to utilize the same physical effect.« less

Observation of the Self-Modulation Instability via Time-Resolved Measurements

DOE PAGES

Gross, M.; Engel, J.; Good, J.; ...

2018-04-06

Self-modulation of an electron beam in a plasma has been observed. The propagation of a long (several plasma wavelengths) electron bunch in an overdense plasma resulted in the production of multiple bunches via the self-modulation instability. Using a combination of a radio-frequency deflector and a dipole spectrometer, the time and energy structure of the self-modulated beam was measured. The longitudinal phase space measurement showed the modulation of a long electron bunch into three bunches with an approximatelymore » $$200\\text{ }\\text{ }\\mathrm{keV}/c$$ amplitude momentum modulation. Demonstrating this effect is a breakthrough for proton-driven plasma accelerator schemes aiming to utilize the same physical effect.« less

OGO 5 observations of Pc 5 waves - Particle flux modulations

NASA Technical Reports Server (NTRS)

Kokubun, S.; Kivelson, M. G.; Mcpherron, R. L.; Russell, C. T.; West, H. I., Jr.

1977-01-01

An investigation is conducted concerning the modulations of particle fluxes associated with Pc 5 waves in the region beyond the plasmapause. A study of thermal flux modulations indicates that some of the density enhancements observed are not spatial structures but are spurious features caused by temporal flux variations associated with hydromagnetic waves. A resonance model of the energetic particle flux modulations is discussed. Energetic particle modulations are also considered. The reported observations reveal that modulations are dominant at energies of about 100 keV for electrons and at 100 keV to 1 MeV for protons. This may indicate that the bounce resonance interaction is not important for Pc 5 waves.

Design of a Nested Eight-Channel Sodium and Four-Channel Proton Coil for 7 Tesla Knee Imaging

PubMed Central

Brown, Ryan; Madelin, Guillaume; Lattanzi, Riccardo; Chang, Gregory; Regatte, Ravinder R.; Sodickson, Daniel K.; Wiggins, Graham C.

2012-01-01

The critical design aim for a dual-tuned sodium/proton coil is to maximize sodium sensitivity and transmit field (B1+) homogeneity while simultaneously providing adequate proton sensitivity and homogeneity. While most dual-frequency coils utilize lossy high-impedance trap circuits or PIN diodes to allow dual-resonance, we explored a nested-coil design for sodium/proton knee imaging at 7T. A stand-alone eight-channel sodium receive array was implemented without standard dual-resonance circuitry to provide improved sodium signal-to-noise ratio (SNR) over a volume coil. A detunable sodium birdcage was added for homogeneous sodium excitation and a four-channel proton transmit-receive array was added to provide anatomical reference imaging and B0 shimming capability. Both modules were implemented with minimal disturbance to the eight-channel sodium array by managing their respective resonances and geometrical arrangement. In vivo sodium SNR was 1.2 to 1.7 times greater in the developed eight-channel array than in a mono-nuclear sodium birdcage coil, while the developed four-channel proton array provided SNR similar to that of a commercial mono-nuclear proton birdcage coil. PMID:22887123

Protonation States in molecular dynamics simulations of peptide folding and binding.

PubMed

Ben-Shimon, Avraham; Shalev, Deborah E; Niv, Masha Y

2013-01-01

Peptides are important signaling modules, acting both as individual hormones and as parts of larger molecules, mediating their protein-protein interactions. Many peptidic and peptidomimetic drugs have reached the marketplace and opportunities for peptide-based drug discovery are on the rise. pH-dependent behavior of peptides is well documented in the context of misfolding diseases and peptide translocation. Changes in the protonation states of peptide residues often have a crucial effect on a peptide's structure, dynamics and function, which may be exploited for biotechnological applications. The current review surveys the increasing levels of sophistication in the treatment of protonation states in computational studies involving peptides. Specifically we describe I) the common practice of assigning a single protonation state and using it throughout the dynamic simulation, II) approaches that consider multiple protonation states and compare computed observables to experimental ones, III) constant pH molecular dynamics methods that couple changes in protonation states with conformational dynamics "on the fly". Applications of conformational dynamics treatment of peptides in the context of binding, folding and interactions with the membrane are presented, illustrating the growing body of work in this field and highlighting the importance of careful handling of protonation states of peptidic residues.

Proton therapy to the subdiaphragmatic region in the management of patients with Hodgkin lymphoma.

PubMed

Sachsman, Suzanne; Hoppe, Bradford S; Mendenhall, Nancy P; Holtzman, Adam; Li, Zuofeng; Slayton, William; Joyce, Mike; Sandler, Eric; Flampouri, Stella

2015-07-01

Twelve consecutive patients with classical Hodgkin lymphoma (HL) involving diaphragmatic or subdiaphragmatic regions were treated on an institutional review board-approved outcomes tracking protocol. All patients underwent treatment with proton therapy following chemotherapy and had comparative three-dimensional conformal photon radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans to evaluate differences in dose to organs at risk (OARs). Among the cohort, stomach doses with 3DCRT, IMRT and proton therapy were 21 Gy (median), 14 Gy and 6 Gy, respectively. Median dose reductions with proton therapy compared with 3DCRT and IMRT were 13 Gy (p = 0.0022) and 8 Gy (p = 0.0022) for the stomach. Additionally, there was significant dose reduction using proton therapy for the liver, pancreas, bowel, left kidney and right kidney. Proton therapy reduces the dose to the stomach, liver, pancreas, small bowel and kidneys compared with 3DCRT or IMRT in patients with HL requiring abdominal radiotherapy. These dose reductions are expected to translate into lower risks of secondary cancers and other late toxicities in survivors of HL.

A Dosimetric Comparison of Proton and Intensity Modulated Radiation Therapy in Pediatric Rhabdomyosarcoma Patients Enrolled on a Prospective Phase II Proton Study

PubMed Central

Ladra, Matthew M.; Edgington, Samantha K.; Mahajan, Anita; Grosshans, David; Szymonifka, Jackie; Khan, Fazal; Moteabbed, Maryam; Friedmann, Alison M.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

2015-01-01

Background Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects. Methods Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans. Results Target coverage was comparable between PT and IMRT plans with a mean CTV V95 of 100% for both modalities (p=0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0-4.9). By site, mean integral dose for IMRT was 1.8 times higher for H&N (p<0.01) and GU (p=0.02), 2.0 times higher for trunk/extremity (p<0.01), and 3.5 times higher for orbit (p<0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for orbital, head and neck, pelvic, and trunk/extremity patients. Conclusions Proton radiation lowers integral dose and improves normal tissue sparing when compared to IMRT for pediatric RMS. Correlation with clinical outcomes is necessary once mature long-term toxicity data are available. PMID:25443861

A Flexible Nested Sodium and Proton Coil Array with Wideband Matching for Knee Cartilage MRI at 3 Tesla

PubMed Central

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Alon, Leeor; Chang, Gregory; Sodickson, Daniel K.; Regatte, Ravinder R.; Wiggins, Graham C.

2015-01-01

Purpose We describe a 6×2 channel sodium/proton array for knee MRI at 3 Tesla. Multi-element coil arrays are desirable because of well-known signal-to-noise ratio advantages over volume and single-element coils. However, low coil-tissue coupling that is characteristic of coils operating at low frequency can make the potential gains from a phased array difficult to realize. Methods The issue of low coil-tissue coupling in the developed six channel sodium receive array was addressed by implementing 1) a mechanically flexible former to minimize coil-to-tissue distance and reduce the overall diameter of the array and 2) a wideband matching scheme that counteracts preamplifier noise degradation caused by coil coupling and a high quality factor. The sodium array was complemented with a nested proton array to enable standard MRI. Results The wideband matching scheme and tight-fitting mechanical design contributed to greater than 30% central SNR gain on the sodium module over a mono-nuclear sodium birdcage coil, while the performance of the proton module was sufficient for clinical imaging. Conclusion We expect the strategies presented in this work to be generally relevant in high density receive arrays, particularly in x-nuclei or small animal applications, or in those where the array is distant from the targeted tissue. PMID:26502310

A cost-effective monitoring technique in particle therapy via uncollimated prompt gamma peak integration

NASA Astrophysics Data System (ADS)

Krimmer, J.; Angellier, G.; Balleyguier, L.; Dauvergne, D.; Freud, N.; Hérault, J.; Létang, J. M.; Mathez, H.; Pinto, M.; Testa, E.; Zoccarato, Y.

2017-04-01

For the purpose of detecting deviations from the prescribed treatment during particle therapy, the integrals of uncollimated prompt gamma-ray timing distributions are investigated. The intention is to provide information, with a simple and cost-effective setup, independent from monitoring devices of the beamline. Measurements have been performed with 65 MeV protons at a clinical cyclotron. Prompt gamma-rays emitted from the target are identified by means of time-of-flight. The proton range inside the PMMA target has been varied via a modulator wheel. The measured variation of the prompt gamma peak integrals as a function of the modulator position is consistent with simulations. With detectors covering a solid angle of 25 msr (corresponding to a diameter of 3-4 in. at a distance of 50 cm from the beam axis) and 108 incident protons, deviations of a few per cent in the prompt gamma-ray count rate can be detected. For the present configuration, this change in the count rate corresponds to a 3 mm change in the proton range in a PMMA target. Furthermore, simulation studies show that a combination of the signals from multiple detectors may be used to detect a misplacement of the target. A different combination of these signals results in a precise number of the detected prompt gamma rays, which is independent on the actual target position.

Pcetk: A pDynamo-based Toolkit for Protonation State Calculations in Proteins.

PubMed

Feliks, Mikolaj; Field, Martin J

2015-10-26

Pcetk (a pDynamo-based continuum electrostatic toolkit) is an open-source, object-oriented toolkit for the calculation of proton binding energetics in proteins. The toolkit is a module of the pDynamo software library, combining the versatility of the Python scripting language and the efficiency of the compiled languages, C and Cython. In the toolkit, we have connected pDynamo to the external Poisson-Boltzmann solver, extended-MEAD. Our goal was to provide a modern and extensible environment for the calculation of protonation states, electrostatic energies, titration curves, and other electrostatic-dependent properties of proteins. Pcetk is freely available under the CeCILL license, which is compatible with the GNU General Public License. The toolkit can be found on the Web at the address http://github.com/mfx9/pcetk. The calculation of protonation states in proteins requires a knowledge of pKa values of protonatable groups in aqueous solution. However, for some groups, such as protonatable ligands bound to protein, the pKa aq values are often difficult to obtain from experiment. As a complement to Pcetk, we revisit an earlier computational method for the estimation of pKa aq values that has an accuracy of ± 0.5 pKa-units or better. Finally, we verify the Pcetk module and the method for estimating pKa aq values with different model cases.

Artificial synapse network on inorganic proton conductor for neuromorphic systems.

PubMed

Zhu, Li Qiang; Wan, Chang Jin; Guo, Li Qiang; Shi, Yi; Wan, Qing

2014-01-01

The basic units in our brain are neurons, and each neuron has more than 1,000 synapse connections. Synapse is the basic structure for information transfer in an ever-changing manner, and short-term plasticity allows synapses to perform critical computational functions in neural circuits. Therefore, the major challenge for the hardware implementation of neuromorphic computation is to develop artificial synapse network. Here in-plane lateral-coupled oxide-based artificial synapse network coupled by proton neurotransmitters are self-assembled on glass substrates at room-temperature. A strong lateral modulation is observed due to the proton-related electrical-double-layer effect. Short-term plasticity behaviours, including paired-pulse facilitation, dynamic filtering and spatiotemporally correlated signal processing are mimicked. Such laterally coupled oxide-based protonic/electronic hybrid artificial synapse network proposed here is interesting for building future neuromorphic systems.

Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

NASA Astrophysics Data System (ADS)

Tang, Grace; Earl, Matthew A.; Yu, Cedric X.

2009-11-01

Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc™ deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to <=± 5°. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was delivered with a different dose rate, extra mode-up time (xMOT) was needed between the transitions of the successive sectors during delivery. On average, the delivery times of the CDR plans were approximately less than 1 min longer than the treatment times of the VDR plans, with an average of about 0.33 min of xMOT per sector transition. The results have shown that VDR may not be necessary for single-arc IMAT. Using variable angular spacing, VDR RapidArc plans can be implemented into the clinics that are not equipped with the new VDR-enabled machines without compromising the plan quality or treatment efficiency. With a prospective optimization approach using variable angular spacing, CDR delivery times can be further minimized while maintaining the high delivery efficiency of single-arc IMAT treatment.

Critical appraisal of RapidArc radiosurgery with flattening filter free photon beams for benign brain lesions in comparison to GammaKnife: a treatment planning study.

PubMed

Abacioglu, Ufuk; Ozen, Zeynep; Yilmaz, Meltem; Arifoglu, Alptekin; Gunhan, Basri; Kayalilar, Namik; Peker, Selcuk; Sengoz, Meric; Gurdalli, Salih; Cozzi, Luca

2014-05-21

To evaluate the role of RapidArc (RA) for stereotactic radiosurgery (SRS) of benign brain lesions in comparison to GammaKnife (GK) based technique. Twelve patients with vestibular schwannoma (VS, n = 6) or cavernous sinus meningioma (CSM, n = 6) were planned for both SRS using volumetric modulated arc therapy (VMAT) by RA. 104 MV flattening filter free photon beams with a maximum dose rate of 2400 MU/min were selected. Data were compared against plans optimised for GK. A single dose of 12.5 Gy was prescribed. The primary objective was to assess treatment plan quality. Secondary aim was to appraise treatment efficiency. For VS, comparing best GK vs. RA plans, homogeneity was 51.7 ± 3.5 vs. 6.4 ± 1.5%; Paddick conformity Index (PCI) resulted 0.81 ± 0.03 vs. 0.84 ± 0.04. Gradient index (PGI) was 2.7 ± 0.2 vs. 3.8 ± 0.6. Mean target dose was 17.1 ± 0.9 vs. 12.9 ± 0.1 Gy. For the brain stem, D(1cm3) was 5.1 ± 2.0 Gy vs 4.8 ± 1.6 Gy. For the ipsilateral cochlea, D(0.1cm3) was 1.7 ± 1.0 Gy vs. 1.8 ± 0.5 Gy. For CSM, homogeneity was 52.3 ± 2.4 vs. 12.4 ± 0.6; PCI: 0.86 ± 0.05 vs. 0.88 ± 0.05; PGI: 2.6 ± 0.1 vs. 3.8 ± 0.5; D(1cm3) to brain stem was 5.4 ± 2.8 Gy vs. 5.2 ± 2.8 Gy; D(0.1cm3) to ipsi-lateral optic nerve was 4.2 ± 2.1 vs. 2.1 ± 1.5 Gy; D(0.1cm3) to optic chiasm was 5.9 ± 3.1 vs. 4.5 ± 2.1 Gy. Treatment time was 53.7 ± 5.8 (64.9 ± 24.3) minutes for GK and 4.8 ± 1.3 (5.0 ± 0.7) minutes for RA for schwannomas (meningiomas). SRS with RA and FFF beams revealed to be adequate and comparable to GK in terms of target coverage, homogeneity, organs at risk sparing with some gain in terms of treatment efficiency.

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

Protonation-dependent conformational dynamics of the multidrug transporter EmrE

PubMed Central

Dastvan, Reza; Mishra, Smriti; Meiler, Jens; Mchaourab, Hassane S.

2016-01-01

The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1–3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient. PMID:26787875

Fundamental radiological and geometric performance of two types of proton beam modulated discrete scanning systems.

PubMed

Farr, J B; Dessy, F; De Wilde, O; Bietzer, O; Schönenberg, D

2013-07-01

The purpose of this investigation was to compare and contrast the measured fundamental properties of two new types of modulated proton scanning systems. This provides a basis for clinical expectations based on the scanned beam quality and a benchmark for computational models. Because the relatively small beam and fast scanning gave challenges to the characterization, a secondary purpose was to develop and apply new approaches where necessary to do so. The following performances of the proton scanning systems were investigated: beamlet alignment, static in-air beamlet size and shape, scanned in-air penumbra, scanned fluence map accuracy, geometric alignment of scanning system to isocenter, maximum field size, lateral and longitudinal field uniformity of a 1 l cubic uniform field, output stability over time, gantry angle invariance, monitoring system linearity, and reproducibility. A range of detectors was used: film, ionization chambers, lateral multielement and longitudinal multilayer ionization chambers, and a scintillation screen combined with a digital video camera. Characterization of the scanned fluence maps was performed with a software analysis tool. The resulting measurements and analysis indicated that the two types of delivery systems performed within specification for those aspects investigated. The significant differences were observed between the two types of scanning systems where one type exhibits a smaller spot size and associated penumbra than the other. The differential is minimum at maximum energy and increases inversely with decreasing energy. Additionally, the large spot system showed an increase in dose precision to a static target with layer rescanning whereas the small spot system did not. The measured results from the two types of modulated scanning types of system were consistent with their designs under the conditions tested. The most significant difference between the types of system was their proton spot size and associated resolution, factors of magnetic optics, and vacuum length. The need and benefit of mutielement detectors and high-resolution sensors was also shown. The use of a fluence map analytical software tool was particularly effective in characterizing the dynamic proton energy-layer scanning.

SU-C-207A-05: Feature Based Water Equivalent Path Length (WEPL) Determination for Proton Radiography by the Technique of Time Resolved Dose Measurement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, R; Jee, K; Sharp, G

Purpose: Studies show that WEPL can be determined from modulated dose rate functions (DRF). However, the previous calibration method based on statistics of the DRF is sensitive to energy mixing of protons due to scattering through different materials (termed as range mixing here), causing inaccuracies in the determination of WEPL. This study intends to explore time-domain features of the DRF to reduce the effect of range mixing in proton radiography (pRG) by this technique. Methods: An amorphous silicon flat panel (PaxScan™ 4030CB, Varian Medical Systems, Inc., Palo Alto, CA) was placed behind phantoms to measure DRFs from a proton beammore » modulated by a specially designed modulator wheel. The performance of two methods, the previously used method based on the root mean square (RMS) and the new approach based on time-domain features of the DRF, are compared for retrieving WEPL and RSP from pRG of a Gammex phantom. Results: Calibration by T{sub 80} (the time point for 80% of the major peak) was more robust to range mixing and produced WEPL with improved accuracy. The error of RSP was reduced from 8.2% to 1.7% for lung equivalent material, with the mean error for all other materials reduced from 1.2% to 0.7%. The mean error of the full width at half maximum (FWHM) of retrieved inserts was decreased from 25.85% to 5.89% for the RMS and T{sub 80} method respectively. Monte Carlo simulations in simplified cases also demonstrated that the T{sub 80} method is less sensitive to range mixing than the RMS method. Conclusion: WEPL images have been retrieved based on single flat panel measured DRFs, with inaccuracies reduced by exploiting time-domain features as the calibration parameter. The T{sub 80} method is validated to be less sensitive to range mixing and can thus retrieve the WEPL values in proximity of interfaces with improved numerical and spatial accuracy for proton radiography.« less

Dosimetric Comparison of Combined Intensity-Modulated Radiotherapy (IMRT) and Proton Therapy Versus IMRT Alone for Pelvic and Para-Aortic Radiotherapy in Gynecologic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berman Milby, Abigail; Both, Stefan, E-mail: both@uphs.upenn.edu; Ingram, Mark

2012-03-01

Purpose: To perform a dosimetric comparison of intensity-modulated radiotherapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT) to the para-aortic (PA) nodal region in women with locally advanced gynecologic malignancies. Methods and Materials: The CT treatment planning scans of 10 consecutive patients treated with IMRT to the pelvis and PA nodes were identified. The clinical target volume was defined by the primary tumor for patients with cervical cancer and by the vagina and paravaginal tissues for patients with endometrial cancer, in addition to the regional lymph nodes. The IMRT, PSPT, and IMPT plans were generated using themore » Eclipse Treatment Planning System and were analyzed for various dosimetric endpoints. Two groups of treatment plans including proton radiotherapy were created: IMRT to pelvic nodes with PSPT to PA nodes (PSPT/IMRT), and IMRT to pelvic nodes with IMPT to PA nodes (IMPT/IMRT). The IMRT and proton RT plans were optimized to deliver 50.4 Gy or Gy (relative biologic effectiveness [RBE)), respectively. Dose-volume histograms were analyzed for all of the organs at risk. The paired t test was used for all statistical comparison. Results: The small-bowel V{sub 20}, V{sub 30}, V{sub 35}, andV{sub 40} were reduced in PSPT/IMRT by 11%, 18%, 27%, and 43%, respectively (p < 0.01). Treatment with IMPT/IMRT demonstrated a 32% decrease in the small-bowel V{sub 20}. Treatment with PSPT/IMRT showed statistically significant reductions in the body V{sub 5-20}; IMPT/IMRT showed reductions in the body V{sub 5-15}. The dose received by half of both kidneys was reduced by PSPT/IMRT and by IMPT/IMRT. All plans maintained excellent coverage of the planning target volume. Conclusions: Compared with IMRT alone, PSPT/IMRT and IMPT/IMRT had a statistically significant decrease in dose to the small and large bowel and kidneys, while maintaining excellent planning target volume coverage. Further studies should be done to correlate the clinical significance of these findings.« less

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Kooy, Hanne M.; Heijmen, Ben J.M.

2015-06-01

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases.more » Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.« less

Mixed protonic and electronic conductors hybrid oxide synaptic transistors

NASA Astrophysics Data System (ADS)

Fu, Yang Ming; Zhu, Li Qiang; Wen, Juan; Xiao, Hui; Liu, Rui

2017-05-01

Mixed ionic and electronic conductor hybrid devices have attracted widespread attention in the field of brain-inspired neuromorphic systems. Here, mixed protonic and electronic conductor (MPEC) hybrid indium-tungsten-oxide (IWO) synaptic transistors gated by nanogranular phosphorosilicate glass (PSG) based electrolytes were obtained. Unique field-configurable proton self-modulation behaviors were observed on the MPEC hybrid transistor with extremely strong interfacial electric-double-layer effects. Temporally coupled synaptic plasticities were demonstrated on the MPEC hybrid IWO synaptic transistor, including depolarization/hyperpolarization, synaptic facilitation and depression, facilitation-stead/depression-stead behaviors, spiking rate dependent plasticity, and high-pass/low-pass synaptic filtering behaviors. MPEC hybrid synaptic transistors may find potential applications in neuron-inspired platforms.

Preliminary results on underground muon bundles observed in the Frejus proton-decay detector

NASA Technical Reports Server (NTRS)

Degrange, B.

1985-01-01

The proton-decay detector installed in the Modane Underground laboratory (4400 mwe) in the Frejus tunnel (French Alps) has recorded 80 880 single muon and 2 322 multi-muon events between March '84 and March '85 (6425 hours of active time). During this period, a part of this modular detector was running, while new modules were being mounted, so that the detector size has continuously increased. The final detector has been completed in May '85.

Studying Solar Wind Properties Around CIRs and Their Effects on GCR Modulation

NASA Astrophysics Data System (ADS)

Ghanbari, K.; Florinski, V. A.

2017-12-01

Corotating interaction region (CIR) events occur when a fast solar wind stream overtakes slow solar wind, forming a compression region ahead and a rarefaction region behind in the fast solar wind. Usually this phenomena occurs along with a crossing of heliospheric current sheet which is the surface separating solar magnetic fields of opposing polarities. In this work, the solar plasma data provided by the ACE science center are utilized to do a superposed epoch analysis on solar parameters including proton density, proton temperature, solar wind speed and solar magnetic field in order to study how the variations of these parameters affect the modulation of galactic cosmic rays. Magnetic fluctuation variances in different parts a of CIR are computed and analyzed using similar techniques in order to understand the cosmic-ray diffusive transport in these regions.

Dosimetric properties of a proton beamline dedicated to the treatment of ocular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

2014-01-15

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

Acid-Sensing Ion Channels Expression, Identity and Role in the Excitability of the Cochlear Afferent Neurons

PubMed Central

González-Garrido, Antonia; Vega, Rosario; Mercado, Francisco; López, Iván A.; Soto, Enrique

2015-01-01

Acid-sensing ion channels (ASICs) are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4) that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs). These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations) and N,N,N’,N’–tetrakis-(2-piridilmetil)-ethylenediamine increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2, and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b, and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs. PMID:26733809

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

DOE PAGES

Adams, T.; Adzic, P.; Ahuja, S.; ...

2016-04-11

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, T.; Adzic, P.; Ahuja, S.

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

MO-F-CAMPUS-T-02: Optimizing Orientations of Hundreds of Intensity-Modulated Beams to Treat Multiple Brain Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Dong, P; Larson, D

Purpose: To investigate a new modulated beam orientation optimization (MBOO) approach maximizing treatment planning quality for the state-of-the-art flattening filter free (FFF) beam that has enabled rapid treatments of multiple brain targets. Methods: MBOO selects and optimizes a large number of intensity-modulated beams (400 or more) from all accessible beam angles surrounding a patient’s skull. The optimization algorithm was implemented on a standalone system that interfaced with the 3D Dicom images and structure sets. A standard published data set that consisted of 1 to 12 metastatic brain tumor combinations was selected for MBOO planning. The planning results from various coplanarmore » and non-coplanar configurations via MBOO were then compared with the results obtained from a clinical volume modulated arc therapy (VMAT) delivery system (Truebeam RapidArc, Varian Oncology). Results: When planning a few number of targets (n<4), MBOO produced results equivalent to non-coplanar multi-arc VMAT planning in terms of target volume coverage and normal tissue sparing. For example, the 12-Gy and 4-Gy normal brain volumes for the 3-target plans differed by less than 1 mL ( 3.0 mLvs 3.8 mL; and 35.2 mL vs 36.3 mL, respectively) for MBOO versus VMAT. However, when planning a larger number of targets (n≥4), MBOO significantly reduced the dose to the normal brain as compared to VMAT, though the target volume coverage was equivalent. For example, the 12-Gy and 4-Gy normal brain volumes for the 12-target plans were 10.8 mL vs. 18.0 mL and 217.9 mL vs. 390.0 mL, respectively for the non-coplanar MBOO versus the non-coplanar VMAT treatment plans, yielding a reduction in volume of more than 60% for the case. Conclusion: MBOO is a unique approach for maximizing normal tissue sparing when treating a large number (n≥4) of brain tumors with FFF linear accelerators. Dr Ma and Dr Sahgal are currently on the board of international society of stereotactic radiosurgery. Dr Sahgal has received support for educational presentations from Elekta company.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scorsetti, Marta; Bignardi, Mario; Clivio, Alessandro

Purpose: A planning study was performed to evaluate RapidArc (RA), a volumetric modulated arc technique, on malignant pleural mesothelioma. The benchmark was conventional fixed-field intensity-modulated radiotherapy (IMRT). Methods and materials: The computed tomography data sets of 6 patients were included. The plans for IMRT with nine fixed beams were compared against double-modulated arcs with a single isocenter. All plans were optimized for 15-MV photon beams. The dose prescription was 54 Gy to the planning target volume. The planning objectives for the planning target volume were a minimal dose of >95% and maximal dose of <107%. For the organs at risk,more » the parameters were as follows: contralateral lung, percentage of volume receiving 5 Gy (V{sub 5Gy}) <60%, V{sub 20Gy} < 10%, mean <10.0 Gy; liver, V{sub 30Gy} <33%, mean <31 Gy; heart, V{sub 45Gy} <30%, V{sub 50Gy} <20%, dose received by 1% of the volume (D{sub 1%}) <60 Gy; contralateral kidney, V{sub 15Gy} <20%; spine, D{sub 1%} <45 Gy; esophagus, V{sub 55Gy} <30%; and spleen, V{sub 40Gy} <50%. The monitor units (MUs) and delivery time were scored to measure the treatment efficiency. The pretreatment portal dosimetry scored delivery to the calculation agreement with the Gamma Agreement Index. Results: RA and IMRT provided equivalent coverage and homogeneity. Both techniques fulfilled objectives on organs at risk with a tendency of RA to improve sparing. The conformity index was 1.9 {+-} 0.1 for RA and IMRT. The number of MU/2Gy was 734 {+-} 82 for RA and 2,195 {+-} 317 for IMRT. The planning vs. delivery agreement revealed a Gamma Agreement Index for IMRT of 96.0% {+-} 2.6% and for RA of 95.7% {+-} 1.5%. The treatment time was 3.7 {+-} 0.3min for RA and 13.4 {+-} 0.1min for IMRT. Conclusion: RA demonstrated compared with conventional IMRT, similar target coverage and better dose sparing to the organs at risks. The number of MUs and the time required to deliver a 2-Gy fraction were much lower for RA, allowing the possibility to incorporate this technique in the treatment options for mesothelioma patients.« less

Volumetric modulated arc radiotherapy for esophageal cancer.

PubMed

Vivekanandan, Nagarajan; Sriram, Padmanaban; Kumar, S A Syam; Bhuvaneswari, Narayanan; Saranya, Kamalakannan

2012-01-01

A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc (RA) against 3D conformal radiation therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT) techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA plans were generated with the aim to spare organs at risk (OAR) and healthy tissue while enforcing highly conformal target coverage. The planning objective was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans were evaluated based on target conformity and dose-volume histograms of organs at risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery time were also evaluated to measure the treatment efficiency. The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT. Target conformity improved with RA plans compared with IMRT. The mean lung dose was similar in all techniques. However, RA plans showed a reduction in the volume of the lung irradiated at V(₂₀Gy) and V(₃₀Gy) dose levels (range, 4.62-17.98%) compared with IMRT plans. The mean dose and D(₃₅%) of heart for the RA plans were better than the IMRT by 0.5-5.8%. Mean V(₁₀Gy) and integral dose to healthy tissue were almost similar in all techniques. But RA plans resulted in a reduced low-level dose bath (15-20 Gy) in the range of 14-16% compared with IMRT plans. The average MU needed to deliver the prescribed dose by RA technique was reduced by 20-25% compared with IMRT technique. The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time, whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-628: Predicted Risk of Post-Irradiation Cerebral Necrosis in Pediatric Brain Cancer Patients: A Treatment Planning Comparison of Proton Vs. Photon Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freund, D; Zhang, R; Sanders, M

Purpose: Post-irradiation cerebral necrosis (PICN) is a severe late effect that can Result from brain cancers treatment using radiation therapy. The purpose of this study was to compare the treatment plans and predicted risk of PICN after volumetric modulated arc therapy (VMAT) to the risk after passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT) in a cohort of pediatric patients. Methods: Thirteen pediatric patients with varying age and sex were selected for this study. A clinical treatment volume (CTV) was constructed for 8 glioma patients and 5 ependymoma patients. Prescribed dose was 54 Gy over 30 fractionsmore » to the planning volume. Dosimetric endpoints were compared between VMAT and proton plans. The normal tissue complication probability (NTCP) following VMAT and proton therapy planning was also calculated using PICN as the biological endpoint. Sensitivity tests were performed to determine if predicted risk of PICN was sensitive to positional errors, proton range errors and selection of risk models. Results: Both PSPT and IMPT plans resulted in a significant increase in the maximum dose and reduction in the total brain volume irradiated to low doses compared with the VMAT plans. The average ratios of NTCP between PSPT and VMAT were 0.56 and 0.38 for glioma and ependymoma patients respectively and the average ratios of NTCP between IMPT and VMAT were 0.67 and 0.68 for glioma and ependymoma plans respectively. Sensitivity test revealed that predicted ratios of risk were insensitive to range and positional errors but varied with risk model selection. Conclusion: Both PSPT and IMPT plans resulted in a decrease in the predictive risk of necrosis for the pediatric plans studied in this work. Sensitivity analysis upheld the qualitative findings of the risk models used in this study, however more accurate models that take into account dose and volume are needed.« less

Multifield optimization intensity modulated proton therapy for head and neck tumors: a translation to practice.

PubMed

Frank, Steven J; Cox, James D; Gillin, Michael; Mohan, Radhe; Garden, Adam S; Rosenthal, David I; Gunn, G Brandon; Weber, Randal S; Kies, Merrill S; Lewin, Jan S; Munsell, Mark F; Palmer, Matthew B; Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X Ronald

2014-07-15

We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment "spot by spot" and "layer by layer." Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-755: Timing Characteristics of Proton and Carbon Ion Treatments Using a Synchrotron and Modulated Scanning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, J; Li, Y; Huang, Z

2015-06-15

Purpose: The time required to deliver a treatment impacts not only the number of patients that can be treated each day but also the accuracy of delivery due to potential movements of patient tissues. Both macroscopic and microscopic timing characteristics of a beam delivery system were studied to examine their impacts on patient treatments. Methods: 35 patients were treated during a clinical trial to demonstrate safety and efficacy of a Siemens Iontris system prior to receiving approval from the Chinese Food and Drug Administration. The system has a variable cycle time and can provide proton beams from 48 to 221more » MeV/n and carbon ions from 86 to 430 MeV/n. A modulated scanning beam delivery technique is used where the beam remains stationary at each spot aiming location and is not turned off while the spot quickly moves from one aiming location to the next. The treatment log files for 28 of the trial patients were analyzed to determine several timing characteristics. Results: The average portal time per target dose was 172.5 s/Gy for protons and 150.7 s/Gy for carbon ions. The maximum delivery time for any portal was less than 300 s. The average dwell time per spot was 12 ms for protons and 3.0 ms for carbon ions. The number of aiming positions per energy layer varied from 1 to 258 for protons and 1 to 621 for carbon ions. The average spill time and cycle time per energy layer were 1.20 and 2.68 s for protons and 0.95 and 4.73 s for carbon ions respectively. For 3 of the patients, the beam was gated on and off to reduce the effects of respiration. Conclusion: For a typical target volume of 153 cc as used in this clinical trial, the portal delivery times were acceptable.« less

Experimental validation of beam quality correction factors for proton beams

NASA Astrophysics Data System (ADS)

Gomà, Carles; Hofstetter-Boillat, Bénédicte; Safai, Sairos; Vörös, Sándor

2015-04-01

This paper presents a method to experimentally validate the beam quality correction factors (kQ) tabulated in IAEA TRS-398 for proton beams and to determine the kQ of non-tabulated ionization chambers (based on the already tabulated values). The method is based exclusively on ionometry and it consists in comparing the reading of two ionization chambers under the same reference conditions in a proton beam quality Q and a reference beam quality 60Co. This allows one to experimentally determine the ratio between the kQ of the two ionization chambers. In this work, 7 different ionization chamber models were irradiated under the IAEA TRS-398 reference conditions for 60Co beams and proton beams. For the latter, the reference conditions for both modulated beams (spread-out Bragg peak field) and monoenergetic beams (pseudo-monoenergetic field) were studied. For monoenergetic beams, it was found that the experimental kQ values obtained for plane-parallel chambers are consistent with the values tabulated in IAEA TRS-398; whereas the kQ values obtained for cylindrical chambers are not consistent—being higher than the tabulated values. These results support the suggestion (of previous publications) that the IAEA TRS-398 reference conditions for monoenergetic proton beams should be revised so that the effective point of measurement of cylindrical ionization chambers is taken into account when positioning the reference point of the chamber at the reference depth. For modulated proton beams, the tabulated kQ values of all the ionization chambers studied in this work were found to be consistent with each other—except for the IBA FC65-G, whose experimental kQ value was found to be 0.6% lower than the tabulated one. The kQ of the PTW Advanced Markus chamber, which is not tabulated in IAEA TRS-398, was found to be 0.997 ± 0.042 (k = 2), based on the tabulated value of the PTW Markus chamber.

SU-E-T-586: Field Size Dependence of Output Factor for Uniform Scanning Proton Beams: A Comparison of TPS Calculation, Measurement and Monte Carlo Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Y; Singh, H; Islam, M

2014-06-01

Purpose: Output dependence on field size for uniform scanning beams, and the accuracy of treatment planning system (TPS) calculation are not well studied. The purpose of this work is to investigate the dependence of output on field size for uniform scanning beams and compare it among TPS calculation, measurements and Monte Carlo simulations. Methods: Field size dependence was studied using various field sizes between 2.5 cm diameter to 10 cm diameter. The field size factor was studied for a number of proton range and modulation combinations based on output at the center of spread out Bragg peak normalized to amore » 10 cm diameter field. Three methods were used and compared in this study: 1) TPS calculation, 2) ionization chamber measurement, and 3) Monte Carlos simulation. The XiO TPS (Electa, St. Louis) was used to calculate the output factor using a pencil beam algorithm; a pinpoint ionization chamber was used for measurements; and the Fluka code was used for Monte Carlo simulations. Results: The field size factor varied with proton beam parameters, such as range, modulation, and calibration depth, and could decrease over 10% from a 10 cm to 3 cm diameter field for a large range proton beam. The XiO TPS predicted the field size factor relatively well at large field size, but could differ from measurements by 5% or more for small field and large range beams. Monte Carlo simulations predicted the field size factor within 1.5% of measurements. Conclusion: Output factor can vary largely with field size, and needs to be accounted for accurate proton beam delivery. This is especially important for small field beams such as in stereotactic proton therapy, where the field size dependence is large and TPS calculation is inaccurate. Measurements or Monte Carlo simulations are recommended for output determination for such cases.« less

MO-FG-CAMPUS-TeP3-05: Limitations of the Dose Weighted LET Concept for Intensity Modulated Proton Therapy in the Distal Falloff Region and Beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moskvin, V; Pirlepesov, F; Farr, J

2016-06-15

Purpose: Dose-weighted linear energy transfer (dLET) has been shown to be useful for the analysis of late effects in proton therapy. This study presents the results of the testing of the dLET concept for intensity modulated proton therapy (IMPT) with a discrete spot scanning beam system without use of an aperture or compensator (AC). Methods: IMPT (no AC) and broad beams (BB) with (AC) were simulated in the TOPAS and FLUKA code systems. Information from the independently tested Monte Carlo Damage Simulation (MCDS) was integrated into the FLUKA code systems to account for spatial variations in the RBE for protonsmore » and other light ions using an endpoint of DNA double strand break (DSB) induction. Results: The proton spectra for IMPT beams at the depths beyond the distal edge contain a tail of high energy protons up to 100 MeV. The integral from the tail is compatible with the number of 5–8 MeV protons at the tip of the Bragg peak (BP). The dose averaged energy (dEav) decreases to 7 MeV at the tip of (BP) and then increases to about 15 MeV beyond the distal edge. Neutrons produced in the nozzle are two orders of magnitude higher for BB with AC than for IMPT in low energy part of the spectra. The dLET values beyond of the distal edge of the BP are 5 times larger for the IMPT than for BB with the AC. Contrarily, negligible differences are seen in the RBE estimates for IMPT and BB with AC beyond the distal edge of the BP. Conclusion: The analysis of late effects in IMPT with a spot scanning and double scattering or scanning techniques with AC may requires both dLET and RBE as quantitative parameters to characterize effects beyond the distal edge of the BP.« less

Pseudo-diode based on protonic/electronic hybrid oxide transistor

NASA Astrophysics Data System (ADS)

Fu, Yang Ming; Liu, Yang Hui; Zhu, Li Qiang; Xiao, Hui; Song, An Ran

2018-01-01

Current rectification behavior has been proved to be essential in modern electronics. Here, a pseudo-diode is proposed based on protonic/electronic hybrid indium-gallium-zinc oxide electric-double-layer (EDL) transistor. The oxide EDL transistors are fabricated by using phosphorous silicate glass (PSG) based proton conducting electrolyte as gate dielectric. A diode operation mode is established on the transistor, originating from field configurable proton fluxes within the PSG electrolyte. Current rectification ratios have been modulated to values ranged between ˜4 and ˜50 000 with gate electrode biased at voltages ranged between -0.7 V and 0.1 V. Interestingly, the proposed pseudo-diode also exhibits field reconfigurable threshold voltages. When the gate is biased at -0.5 V and 0.3 V, threshold voltages are set to ˜-1.3 V and -0.55 V, respectively. The proposed pseudo-diode may find potential applications in brain-inspired platforms and low-power portable systems.

Simulation of Spatial and Temporal Radiation Exposures for ISS in the South Atlantic Anomaly

NASA Technical Reports Server (NTRS)

Anderson, Brooke M.; Nealy, John E.; Luetke, Nathan J.; Sandridge, Christopher A.; Qualls, Garry D.

2004-01-01

The International Space Station (ISS) living areas receive the preponderance of ionizing radiation exposure from Galactic Cosmic Rays (GCR) and geomagnetically trapped protons. Practically all trapped proton exposure occurs when the ISS passes through the South Atlantic Anomaly (SAA) region. The fact that this region is in proximity to a trapping mirror point indicates that the proton flux is highly directional. The inherent shielding provided by the ISS structure is represented by a recently-developed CAD model of the current 11-A configuration. Using modeled environment and configuration, trapped proton exposures have been analytically estimated at selected target points within the Service and Lab Modules. The results indicate that the directional flux may lead to substantially different exposure characteristics than the more common analyses that assume an isotropic environment. Additionally, predictive capability of the computational procedure should allow sensitive validation with corresponding on-board directional dosimeters.

Proton-Controlled Organic Microlaser Switch.

PubMed

Gao, Zhenhua; Zhang, Wei; Yan, Yongli; Yi, Jun; Dong, Haiyun; Wang, Kang; Yao, Jiannian; Zhao, Yong Sheng

2018-05-25

Microscale laser switches have been playing irreplaceable roles in the development of photonic devices with high integration levels. However, it remains a challenge to switch the lasing wavelengths across a wide range due to relatively fixed energy bands in traditional semiconductors. Here, we report a strategy to switch the lasing wavelengths among multiple states based on a proton-controlled intramolecular charge-transfer (ICT) process in organic dye-doped flexible microsphere resonant cavities. The protonic acids can effectively bind onto the ICT molecules, which thus enhance the ICT strength of the dyes and lead to a red-shifted gain behavior. On this basis, the gain region was effectively modulated by using acids with different proton-donating ability, and as a result, laser switching among multiple wavelengths was achieved. The results will provide guidance for the rational design of miniaturized lasers with performances based on the characteristic of organic optoelectronic materials.

MICRODOSIMETRIC MEASUREMENT OF SECONDARY RADIATION IN THE PASSIVE SCATTERED PROTON THERAPY ROOM OF iTHEMBA LABS USING A TISSUE-EQUIVALENT PROPORTIONAL COUNTER.

PubMed

Chiriotti, S; Parisi, A; Vanhavere, F; De Saint-Hubert, M; Vandevoorde, C; Slabbert, J; Beukes, P; de Kock, E; Symons, J

2018-04-13

Measurements of the dose equivalent at different distances from the isocenter of the proton therapy center at iThemba LABS were previously performed with a tissue-equivalent proportional counter (TEPC). These measurements showed that the scattered radiation levels were one or two orders of magnitude higher in comparison to other passive scattering delivery systems. In order to reduce these radiation levels, additional shielding was installed shortly after the measurements were done. Therefore, the aim of this work is to quantify and assess the reduction of the secondary doses delivered in the proton therapy room at iThemba LABS after the installation of the additional shielding. This has been performed by measuring microdosimetric spectra with a TEPC at 11 locations around the isocenter when a clinical modulated beam of 200 MeV proton was impinging onto a water phantom placed at the isocenter.

Copper-Containing Nitrite Reductase Employing Proton-Coupled Spin-Exchanged Electron-Transfer and Multiproton Synchronized Transfer to Reduce Nitrite.

PubMed

Qin, Xin; Deng, Li; Hu, Caihong; Li, Li; Chen, Xiaohua

2017-10-20

The possible catalytic mechanism of the reduction of nitrite by copper-containing nitrite reductases (CuNiRs) is examined by using the M06 function according to two copper models, which include type-one copper (T1Cu) and type-two copper (T2Cu) sites. Examinations confirm that the protonation of two residues, His255 and Asp98, near the T2Cu site, can modulate the redox states of T1Cu and T2Cu, but cannot directly cause electron transfer from T1Cu to T2Cu. The electron hole remains at the T2Cu site when only one residue, His255 or Asp98, is protonated. However, the hole resides at the T1Cu site when both His255 and Asp98 are protonated. Then, the first protonation of nitrite takes place through indirect proton transfer from protonated His255 through the bridging H 2 O and Asp98 with three protons moving together, which cannot cause the cleavage of the HO-NO bond. Subsequently, the substrate is required to obtain another proton from reprotonated His255 through the bridging H 2 O. The reprotonation of nitrite induces the generation of nitric oxide (NO) and H 2 O at the T2Cu site through a special double-proton-coupled spin-exchanged electron-transfer mechanism with indirect proton transfer from His255 to the substrate, a beta-electron of T2Cu I shift to the NO cation, and the remaining alpha-electron changing spin direction at the same time. These results may provide useful information to better understand detailed proton-/electron-transfer reactions for the catalytic processes of CuNiR. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, R; Jee, K; Sharp, G

Purpose: Proton radiography, which images the patients with the same type of particles that they are to be treated with, is a promising approach for image guidance and range uncertainties reduction. This study aimed to realize quality proton radiography by measuring dose rate functions (DRF) in time domain using a single flat panel and retrieve water equivalent path length (WEPL) from them. Methods: An amorphous silicon flat panel (PaxScan™ 4030CB, Varian Medical Systems, Inc., Palo Alto, CA) was placed behind phantoms to measure DRFs from a proton beam modulated by the modulator wheel. To retrieve WEPL and RSP, calibration modelsmore » based on the intensity of DRFs only, root mean square (RMS) of DRFs only and the intensity weighted RMS were tested. The quality of obtained WEPL images (in terms of spatial resolution and level of details) and the accuracy of WEPL were compared. Results: RSPs for most of the Gammex phantom inserts were retrieved within ± 1% errors by calibration models based on the RMS and intensity weighted RMS. The mean percentage error for all inserts was reduced from 1.08% to 0.75% by matching intensity in the calibration model. In specific cases such as the insert with a titanium rod, the calibration model based on RMS only fails while the that based on intensity weighted RMS is still valid. The quality of retrieved WEPL images were significantly improved for calibration models including intensity matching. Conclusion: For the first time, a flat panel, which is readily available in the beamline for image guidance, was tested to acquire quality proton radiography with WEPL accurately retrieved from it. This technique is promising to be applied for image-guided proton therapy as well as patient specific RSP determination to reduce uncertainties of beam ranges.« less

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy

NASA Astrophysics Data System (ADS)

Hälg, R. A.; Besserer, J.; Boschung, M.; Mayer, S.; Lomax, A. J.; Schneider, U.

2014-05-01

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients.

PubMed

Ling, Ted C; Slater, Jerry M; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M; Patyal, Baldev; Slater, Jerry D; Yang, Gary Y

2014-12-05

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy.

PubMed

Hälg, R A; Besserer, J; Boschung, M; Mayer, S; Lomax, A J; Schneider, U

2014-05-21

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

PubMed Central

Ling, Ted C.; Slater, Jerry M.; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M.; Patyal, Baldev; Slater, Jerry D.; Yang, Gary Y.

2014-01-01

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients. PMID:25489937

Cosmonaut Dezhurov Talks With Flight Controllers

NASA Technical Reports Server (NTRS)

2001-01-01

Aboard the International Space Station (ISS), Cosmonaut and Expedition Three flight engineer Vladimir N. Dezhurov, representing Rosaviakosmos, talks with flight controllers from the Zvezda Service Module. Russian-built Zvezda is linked to the Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the Station, providing living quarters, a life support system, electrical power distribution, a data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.

International Space Station (ISS)

NASA Image and Video Library

2001-09-16

Aboard the International Space Station (ISS), Cosmonaut and Expedition Three flight engineer Vladimir N. Dezhurov, representing Rosaviakosmos, talks with flight controllers from the Zvezda Service Module. Russian-built Zvezda is linked to the Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the Station, providing living quarters, a life support system, electrical power distribution, a data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.

International Space Station (ISS)

NASA Image and Video Library

2001-12-12

Astronauts Frank L. Culbertson, Jr. (left), Expedition Three mission commander, and Daniel W. Bursch, Expedition Four flight engineer, work in the Russian Zvezda Service Module on the International Space Station (ISS). Zvezda is linked to the Russian built Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the Station, providing living quarters, a life support system, electrical power distribution, a data processing system, a flight control system, and a propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000 pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.

International Space Station (ISS)

NASA Image and Video Library

2001-03-30

Astronaut James S. Voss, Expedition Two flight engineer, performs an electronics task in the Russian Zvezda Service Module on the International Space Station (ISS). Zvezda is linked to the Russian-built Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity, the first U.S.-built component to the ISS. Zvezda (Russian word for star), the third component of the ISS and the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the station, providing living quarters, a life support system, electrical power distribution, a data processing system, a flight control system, and a propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.

International Space Station (ISS)

NASA Image and Video Library

2002-03-25

Cosmonaut Yury I. Onufrienko, Expedition Four mission commander, uses a communication system in the Russian Zvezda Service Module on the International Space Station (ISS). The Zvezda is linked to the Russian-built Functional Cargo Block (FGB) or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the station, providing living quarters, a life support system, electrical power distribution, a data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.

Binding Site Configurations Probe the Structure and Dynamics of the Zinc Finger of NEMO (NF-κB Essential Modulator).

PubMed

Godwin, Ryan C; Melvin, Ryan L; Gmeiner, William H; Salsbury, Freddie R

2017-01-31

Zinc-finger proteins are regulators of critical signaling pathways for various cellular functions, including apoptosis and oncogenesis. Here, we investigate how binding site protonation states and zinc coordination influence protein structure, dynamics, and ultimately function, as these pivotal regulatory proteins are increasingly important for protein engineering and therapeutic discovery. To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), as well as the role of zinc, we present results of 20 μs molecular dynamics trajectories, 5 μs for each of four active site configurations. Consistent with experimental evidence, the zinc ion is essential for mechanical stabilization of the functional, folded conformation. Hydrogen bond motifs are unique for deprotonated configurations yet overlap in protonated cases. Correlated motions and principal component analysis corroborate the similarity of the protonated configurations and highlight unique relationships of the zinc-bound configuration. We hypothesize a potential mechanism for zinc binding from results of the thiol configurations. The deprotonated, zinc-bound configuration alone predominantly maintains its tertiary structure throughout all 5 μs and alludes rare conformations potentially important for (im)proper zinc-finger-related protein-protein or protein-DNA interactions.

Performance of timing Resistive Plate Chambers with protons from 200 to 800 MeV

NASA Astrophysics Data System (ADS)

Machado, J.; Adamczewski-Musch, J.; Blanco, A.; Boretzky, K.; Cabanelas, P.; Cartegni, L.; Ferreira Marques, R.; Fonte, P.; Fruehauf, J.; Galaviz, D.; Heil, M.; Henriques, A.; . Ickert, G.; Körper, D.; Lopes, L.; Palka, M.; Pereira, A.; Rossi, D.; Simon, H.; Teubig, P.; Traxler, M.; Velho, P.; Altstadt, S.; Atar, L.; Aumann, T.; Bemmerer, D.; Caesar, C.; Charpy, A.; Elekes, Z.; Fiori, E.; Gasparic, I.; Gerbig, J.; Göbel, K.; Heftrich, T.; Heine, M.; Heinz, A.; Holl, M.; Ignatov, A.; Isaak, J.; Johansson, H.; Kelic-Heil, A.; Lederer, C.; Lindberg, S.; Löher, B.; Marganiec, J.; Martensson, M.; Nilsson, T.; Panin, V.; Paschalis, S.; Petri, M.; Plag, R.; Pohl, M.; Rastrepina, G.; Reifarth, R.; Reinhardt, T. P.; Röder, M.; Savran, D.; Scheit, H.; Schrock, P.; Silva, J.; Stach, D.; Strannerdahl, F.; Thies, R.; Wagner, A.; Wamers, F.; Weigand, M.

2015-01-01

A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic protons produced from a deuteron beam of varying energy (200 to 800 AMeV) in experiment S406 at GSI, Darmstadt, Germany. The aim of the experiment is to characterize the response of the prototype to protons in this energy range, which deposit from 1.75 to 6 times more energy than minimum ionizing particles. Each layer, with an active area of about 2000 × 500 mm2, is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C2H2F4 and 10% SF6. The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Results show an uniform efficiency close to 100% along with a timing resolution of around 60 ps on the entire 2000 × 500 mm2 area.

Space Shuttle drops down the SAA doses on ISS

NASA Astrophysics Data System (ADS)

Dachev, T. P.; Semkova, J.; Tomov, B.; Matviichuk, Yu.; Dimitrov, Pl.; Koleva, R.; Malchev, St.; Reitz, G.; Horneck, G.; De Angelis, G.; Häder, D.-P.; Petrov, V.; Shurshakov, V.; Benghin, V.; Chernykh, I.; Drobyshev, S.; Bankov, N. G.

2011-06-01

Long-term analysis of data from two radiation detection instruments on the International Space Station (ISS) shows that the docking of the Space Shuttle drops down the measured dose rates in the region of the South Atlantic Anomaly (SAA) by a factor of 1.5-3. Measurements either by the R3DE detector, which is outside the ISS at the EuTEF facility on the Columbus module behind a shielding of less than 0.45 g cm -2, and by the three detectors of the Liulin-5 particle telescope, which is inside the Russian PEARS module in the spherical tissue equivalent phantom behind much heavier shielding demonstrate that effect. Simultaneously the estimated averaged incident energies of the incoming protons rise up from about 30 to 45 MeV. The effect is explained by the additional shielding against the SAA 30-150 MeV protons, provided by the 78 tons Shuttle to the instruments inside and outside of the ISS. An additional reason is the ISS attitude change (performed for the Shuttle docking) leading to decreasing of dose rates in two of Liulin-5 detectors because of the East-West proton fluxes asymmetry in SAA. The Galactic Cosmic Rays dose rates are practically not affected.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Camingue, Pamela; Christian, Rochelle; Ng, Davin

The purpose of this study was to compare 4 different external beam radiation therapy treatment techniques for the treatment of T1-2, N0, M0 glottic cancers: traditional lateral beams with wedges (3D), 5-field intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy. Treatment plans in each technique were created for 10 patients using consistent planning parameters. The photon treatment plans were optimized using Philips Pinnacle{sub 3} v.9 and the IMRT and VMAT plans used the Direct Machine Parameter Optimization algorithm. The proton treatment plans were optimized using Varian Eclipse Proton v.8.9. The prescription used for each plan wasmore » 63 Gy in 28 fractions. The contours for spinal cord, right carotid artery, left carotid artery, and normal tissue were created with respect to the patient's bony anatomy so that proper comparisons of doses could be made with respect to volume. An example of the different isodose distributions will be shown. The data collection for comparison purposes includes: clinical treatment volume coverage, dose to spinal cord, dose to carotid arteries, and dose to normal tissue. Data comparisons will be displayed graphically showing the maximum, mean, median, and ranges of doses.« less

Proton Radiotherapy for Pediatric Bladder/Prostate Rhabdomyosarcoma: Clinical Outcomes and Dosimetry Compared to Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotter, Shane E.; Herrup, David A.; Friedmann, Alison

Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan wasmore » optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses.« less

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer.

PubMed

Wu, Chen-Ta; Motegi, Atsushi; Motegi, Kana; Hotta, Kenji; Kohno, Ryosuke; Tachibana, Hidenobu; Kumagai, Motoki; Nakamura, Naoki; Hojo, Hidehiro; Niho, Seiji; Goto, Koichi; Akimoto, Tetsuo

2016-08-10

To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Proposed linear energy transfer areal detector for protons using radiochromic film.

PubMed

Mayer, Rulon; Lin, Liyong; Fager, Marcus; Douglas, Dan; McDonough, James; Carabe, Alejandro

2015-04-01

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

Feasibility study of proton-based quality assurance of proton range compensator

NASA Astrophysics Data System (ADS)

Park, S.; Jeong, C.; Min, B. J.; Kwak, J.; Lee, J.; Cho, S.; Shin, D.; Lim, Y. K.; Park, S. Y.; Lee, S. B.

2013-06-01

All patient specific range compensators (RCs) are customized for achieving distal dose conformity of target volume in passively scattered proton therapy. Compensators are milled precisely using a computerized machine. In proton therapy, precision of the compensator is critical and quality assurance (QA) is required to protect normal tissues and organs from radiation damage. This study aims to evaluate the precision of proton-based quality assurance of range compensator. First, the geometry information of two compensators was extracted from the DICOM Radiotherapy (RT) plan. Next, RCs were irradiated on the EBT film individually by proton beam which is modulated to have a photon-like percent depth dose (PDD). Step phantoms were also irradiated on the EBT film to generate calibration curve which indicates relationship between optical density of irradiated film and perpendicular depth of compensator. Comparisons were made using the mean absolute difference (MAD) between coordinate information from DICOM RT and converted depth information from the EBT film. MAD over the whole region was 1.7, and 2.0 mm. However, MAD over the relatively flat regions on each compensator selected for comparison was within 1 mm. These results shows that proton-based quality assurance of range compensator is feasible and it is expected to achieve MAD over the whole region less than 1 mm with further correction about scattering effect of proton imaging.

Treatment planning optimisation in proton therapy

PubMed Central

McGowan, S E; Burnet, N G; Lomax, A J

2013-01-01

ABSTRACT. The goal of radiotherapy is to achieve uniform target coverage while sparing normal tissue. In proton therapy, the same sources of geometric uncertainty are present as in conventional radiotherapy. However, an important and fundamental difference in proton therapy is that protons have a finite range, highly dependent on the electron density of the material they are traversing, resulting in a steep dose gradient at the distal edge of the Bragg peak. Therefore, an accurate knowledge of the sources and magnitudes of the uncertainties affecting the proton range is essential for producing plans which are robust to these uncertainties. This review describes the current knowledge of the geometric uncertainties and discusses their impact on proton dose plans. The need for patient-specific validation is essential and in cases of complex intensity-modulated proton therapy plans the use of a planning target volume (PTV) may fail to ensure coverage of the target. In cases where a PTV cannot be used, other methods of quantifying plan quality have been investigated. A promising option is to incorporate uncertainties directly into the optimisation algorithm. A further development is the inclusion of robustness into a multicriteria optimisation framework, allowing a multi-objective Pareto optimisation function to balance robustness and conformity. The question remains as to whether adaptive therapy can become an integral part of a proton therapy, to allow re-optimisation during the course of a patient's treatment. The challenge of ensuring that plans are robust to range uncertainties in proton therapy remains, although these methods can provide practical solutions. PMID:23255545

High Temperature Protonic Conductors

NASA Technical Reports Server (NTRS)

Dynys, Fred; Berger, Marie-Helen; Sayir, Ali

2007-01-01

High Temperature Protonic Conductors (HTPC) with the perovskite structure are envisioned for electrochemical membrane applications such as H2 separation, H2 sensors and fuel cells. Successive membrane commercialization is dependent upon addressing issues with H2 permeation rate and environmental stability with CO2 and H2O. HTPC membranes are conventionally fabricated by solid-state sintering. Grain boundaries and the presence of intergranular second phases reduce the proton mobility by orders of magnitude than the bulk crystalline grain. To enhanced protonic mobility, alternative processing routes were evaluated. A laser melt modulation (LMM) process was utilized to fabricate bulk samples, while pulsed laser deposition (PLD) was utilized to fabricate thin film membranes . Sr3Ca(1+x)Nb(2-x)O9 and SrCe(1-x)Y(x)O3 bulk samples were fabricated by LMM. Thin film BaCe(0.85)Y(0.15)O3 membranes were fabricated by PLD on porous substrates. Electron microscopy with chemical mapping was done to characterize the resultant microstructures. High temperature protonic conduction was measured by impedance spectroscopy in wet air or H2 environments. The results demonstrate the advantage of thin film membranes to thick membranes but also reveal the negative impact of defects or nanoscale domains on protonic conductivity.

Measurements of Cosmic-Ray Proton and Helium Spectra from the BESS-Polar Long-Duration Balloon Flights Over Antarctica

NASA Technical Reports Server (NTRS)

Abe, K.; Fuke, H.; Haino, S.; Hams, T.; Hasegawa, M.; Horikoshi, A.; Itazaki, A.; Kim, K. C.; Kumazawa, T.; Kusumoto, A.;

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verburg, J; Bortfeld, T

Purpose: We present a new system to perform prompt gamma-ray spectroscopy during proton pencil-beam scanning treatments, which enables in vivo verification of the proton range. This system will be used for the first clinical studies of this technology. Methods: After successful pre-clinical testing of prompt gamma-ray spectroscopy, a full scale system for clinical studies is now being assembled. Prompt gamma-rays will be detected during patient treatment using an array of 8 detector modules arranged behind a tungsten collimator. Each detector module consists of a lanthanum(III) bromide scintillator, a photomultiplier tube, and custom electronics for stable high voltage supply and signalmore » amplification. A new real-time data acquisition and control system samples the signals from the detectors with analog-to-digital converters, analyses events of interest, and communicates with the beam delivery systems. The timing of the detected events was synchronized to the cyclotron radiofrequency and the pencil-beam delivery. Range verification is performed by matching measured energy- and timeresolved gamma-ray spectra to nuclear reaction models based on the clinical treatment plan. Experiments in phantoms were performed using clinical beams in order to assess the performance of the systems. Results: The experiments showed reliable real-time analysis of more than 10 million detector events per second. The individual detector modules acquired accurate energy- and time-resolved gamma-ray measurements at a rate of 1 million events per second, which is typical for beams delivered with a clinical dose rate. The data acquisition system successfully tracked the delivery of the scanned pencil-beams to determine the location of range deviations within the treatment field. Conclusion: A clinical system for proton range verification using prompt gamma-ray spectroscopy has been designed and is being prepared for use during patient treatments. We anticipate to start a first clinical study in the near future. This work was supported by the Federal Share of program income earned by Massachusetts; General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center.« less

SU-E-T-470: Beam Performance of the Radiance 330 Proton Therapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nazaryan, H; Nazaryan, V; Wang, F

2014-06-01

Purpose: The ProTom Radiance 330 proton radiotherapy system is a fully functional, compact proton radiotherapy system that provides advanced proton delivery capabilities. It supports three-dimensional beam scanning with energy and intensity modulation. A series of measurements have been conducted to characterize the beam performance of the first installation of the system at the McLaren Proton Therapy Center in Flint, Michigan. These measurements were part of the technical commissioning of the system. Select measurements and results are presented. Methods: The Radiance 330 proton beam energy range is 70–250 MeV for treatment, and up to 330 MeV for proton tomography and radiography.more » Its 3-D scanning capability, together with a small beam emittance and momentum spread, provides a highly efficient beam delivery. During the technical commissioning, treatment plans were created to deliver uniform maps at various energies to perform Gamma Index analysis. EBT3 Gafchromic films were irradiated using the Planned irradiation maps. Bragg Peak chamber was used to test the dynamic range during a scan in one layer for high (250 MeV) and Low (70 MeV) energies. The maximum and minimum range, range adjustment and modulation, distal dose falloff (80%–20%), pencil beam spot size, spot placement accuracy were also measured. The accuracy testing included acquiring images, image registration, receiving correction vectors and applying the corrections to the robotic patient positioner. Results: Gamma Index analysis of the Treatment Planning System (TPS) data vs. Measured data showed more than 90% of points within (3%, 3mm) for the maps created by the TPS. At Isocenter Beam Size (One sigma) < 3mm at highest energy (250 MeV) in air. Beam delivery was within 0.6 mm of the intended target at the entrance and the exit of the beam, through the phantom. Conclusion: The Radiance 330 Beam Performance Measurements have confirmed that the system operates as designed with excellent clinical performance specifications. Hovakim Nazaryan, Vahagn Nazaryan and Fuhua Wang are employees of ProTom International, Inc. who contributed to the development and completed the technical commissioning of the Radiance 330 proton therapy delivery system manufactured by ProTom International.« less

FoCa: a modular treatment planning system for proton radiotherapy with research and educational purposes

NASA Astrophysics Data System (ADS)

Sánchez-Parcerisa, D.; Kondrla, M.; Shaindlin, A.; Carabe, A.

2014-12-01

FoCa is an in-house modular treatment planning system, developed entirely in MATLAB, which includes forward dose calculation of proton radiotherapy plans in both active and passive modalities as well as a generic optimization suite for inverse treatment planning. The software has a dual education and research purpose. From the educational point of view, it can be an invaluable teaching tool for educating medical physicists, showing the insights of a treatment planning system from a well-known and widely accessible software platform. From the research point of view, its current and potential uses range from the fast calculation of any physical, radiobiological or clinical quantity in a patient CT geometry, to the development of new treatment modalities not yet available in commercial treatment planning systems. The physical models in FoCa were compared with the commissioning data from our institution and show an excellent agreement in depth dose distributions and longitudinal and transversal fluence profiles for both passive scattering and active scanning modalities. 3D dose distributions in phantom and patient geometries were compared with a commercial treatment planning system, yielding a gamma-index pass rate of above 94% (using FoCa’s most accurate algorithm) for all cases considered. Finally, the inverse treatment planning suite was used to produce the first prototype of intensity-modulated, passive-scattered proton therapy, using 13 passive scattering proton fields and multi-leaf modulation to produce a concave dose distribution on a cylindrical solid water phantom without any field-specific compensator.

Role of the Coronal Alfvén Speed in Modulating the Solar-wind Helium Abundance

NASA Astrophysics Data System (ADS)

Wang, Y.-M.

2016-12-01

The helium abundance He/H in the solar wind is relatively constant at ˜0.04 in high-speed streams, but varies in phase with the sunspot number in slow wind, from ˜0.01 at solar minimum to ˜0.04 at maximum. Suggested mechanisms for helium fractionation have included frictional coupling to protons and resonant interactions with high-frequency Alfvénic fluctuations. We compare He/H measurements during 1995-2015 with coronal parameters derived from source-surface extrapolations of photospheric field maps. We find that the near-Earth helium abundance is an increasing function of the magnetic field strength and Alfvén speed v A in the outer corona, while being only weakly correlated with the proton flux density. Throughout the solar cycle, fast wind is associated with short-term increases in v A near the source surface; resonance with Alfvén waves, with v A and the relative speed of α-particles and protons decreasing with increasing heliocentric distance, may then lead to enhanced He/H at 1 au. The modulation of helium in slow wind reflects the tendency for the associated coronal Alfvén speeds to rise steeply from sunspot minimum, when this wind is concentrated around the source-surface neutral line, to sunspot maximum, when the source-surface field attains its peak strengths. The helium abundance near the source surface may represent a balance between collisional decoupling from protons and Alfvén wave acceleration.

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yupeng; Niemela, Perttu; Siljamaki, Sami

2015-08-15

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology,more » are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Titt, U; Suzuki, K

Purpose: The PTCH is preparing the ocular proton beam nozzle for clinical use. Currently commissioning measurements are being performed using films, diodes and ionization chambers. In parallel, a Monte Carlo model of the beam line was created for integration into the automated Monte Carlo treatment plan computation system, MC{sup 2}. This work aims to compare Monte Carlo predictions to measured proton doses in order to validate the Monte Carlo model. Methods: A complete model of the double scattering ocular beam line has been created and is capable of simulating proton beams with a comprehensive set of beam modifying devices, includingmore » eleven different range modulator wheels. Simulations of doses in water were scored and compare to ion chamber measurements of depth doses, lateral dose profiles extracted from half beam block exposures of films, and diode measurements of lateral penumbrae at various depths. Results: All comparison resulted in an average relative entrance dose difference of less than 3% and peak dose difference of less than 2%. All range differences were smaller than 0.2 mm. The differences in the lateral beam profiles were smaller than 0.2 mm, and the differences in the penumbrae were all smaller than 0.4%. Conclusion: All available data shows excellent agreement of simulations and measurements. More measurements will have to be performed in order to completely and systematically validate the model. Besides simulating and measuring PDDs and lateral profiles of all remaining range modulator wheels, the absolute dosimetry factors in terms of number of source protons per monitor unit have to be determined.« less

Beyond Gaussians: a study of single spot modeling for scanning proton dose calculation

PubMed Central

Li, Yupeng; Zhu, Ronald X.; Sahoo, Narayan; Anand, Aman; Zhang, Xiaodong

2013-01-01

Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field-size effects on dose output. In the present study, we developed a pencil-beam algorithm for scanning-proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil-beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field-size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy. PMID:22297324

Successful delivery of adjuvant external beam radiotherapy for ependymoma in a patient with Ondine's curse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Mehee; Thoma, Miranda; Tolekidis, George

Ondine's curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine's curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred formore » radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97 mm Hg. He was diagnosed with Ondine's curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.« less

Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time adaptive tumor gating. Concerns about technique and preliminary clinical results.

PubMed

Llacer-Moscardo, Carmen; Riou, Olivier; Azria, David; Bedos, Ludovic; Ailleres, Norbert; Quenet, Francois; Rouanet, Philippe; Ychou, Marc; Fenoglietto, Pascal

2017-01-01

Motion management is a major challenge in abdominal SBRT. We present our study of SBRT for liver tumors using intrafraction motion review (IMR) allowing simultaneous KV information and MV delivery to synchronize the beam during gated RapidArc treatment. Between May 2012 and March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding 5 mm from the ITV. Dose prescription ranged from 40 to 50 Gy in 5-10 fractions. The prescribed dose and fractionation were chosen depending on hepatic function and dosimetric results. Thirty-four patients with a minimal follow-up of six months were analyzed for local control and toxicity. Accuracy for tumor repositioning was evaluated for the first ten patients. With a median follow-up of 13 months, the treatment was well tolerated and no patient presented RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3 patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver enzymes. In-field local control was 90.3% with 7 complete responses, 14 partial responses and 7 stabilisations. 3 patients evolved "in field". 12 patients had an intrahepatic progression "out of field". Mean intrafraction deviation of fiducials in the craneo-caudal direction was 0.91 mm (0-6 mm). The clinical tolerance and oncological outcomes were favorable when using image-guided liver SBRT with real-time adaptive tumor gating.

Protonic/electronic hybrid oxide transistor gated by chitosan and its full-swing low voltage inverter applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Jin Yu; Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201; Zhu, Li Qiang, E-mail: lqzhu@nimte.ac.cn

Modulation of charge carrier density in condensed materials based on ionic/electronic interaction has attracted much attention. Here, protonic/electronic hybrid indium-zinc-oxide (IZO) transistors gated by chitosan based electrolyte were obtained. The chitosan-based electrolyte illustrates a high proton conductivity and an extremely strong proton gating behavior. The transistor illustrates good electrical performances at a low operating voltage of ∼1.0 V such as on/off ratio of ∼3 × 10{sup 7}, subthreshold swing of ∼65 mV/dec, threshold voltage of ∼0.3 V, and mobility of ∼7 cm{sup 2}/V s. Good positive gate bias stress stabilities are obtained. Furthermore, a low voltage driven resistor-loaded inverter was built by using an IZO transistor inmore » series with a load resistor, exhibiting a linear relationship between the voltage gain and the supplied voltage. The inverter is also used for decreasing noises of input signals. The protonic/electronic hybrid IZO transistors have potential applications in biochemical sensors and portable electronics.« less

Coordination-chemistry control of proton conductivity in the iconic metal-organic framework material HKUST-1.

PubMed

Jeong, Nak Cheon; Samanta, Bappaditya; Lee, Chang Yeon; Farha, Omar K; Hupp, Joseph T

2012-01-11

HKUST-1, a metal-organic framework (MOF) material containing Cu(II)-paddlewheel-type nodes and 1,3,5-benzenetricarboxylate struts, features accessible Cu(II) sites to which solvent or other desired molecules can be intentionally coordinated. As part of a broader investigation of ionic conductivity in MOFs, we unexpectedly observed substantial proton conductivity with the "as synthesized" version of this material following sorption of methanol. Although HKUST-1 is neutral, coordinated water molecules are rendered sufficiently acidic by Cu(II) to contribute protons to pore-filling methanol molecules and thereby enhance the alternating-current conductivity. At ambient temperature, the chemical identities of the node-coordinated and pore-filling molecules can be independently varied, thus enabling the proton conductivity to be reversibly modulated. The proton conductivity of HKUST-1 was observed to increase by ~75-fold, for example, when node-coordinated acetonitrile molecules were replaced by water molecules. In contrast, the conductivity became almost immeasurably small when methanol was replaced by hexane as the pore-filling solvent. © 2011 American Chemical Society

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abe, K.; Itazaki, A.; Kusumoto, A.

The BESS-Polar Collaboration measured the energy spectra of cosmic-ray protons and helium during two long-duration balloon flights over Antarctica in 2004 December and 2007 December at substantially different levels of solar modulation. Proton and helium spectra probe the origin and propagation history of cosmic rays in the galaxy, and are essential to calculations of the expected spectra of cosmic-ray antiprotons, positrons, and electrons from interactions of primary cosmic-ray nuclei with the interstellar gas, and to calculations of atmospheric muons and neutrinos. We report absolute spectra at the top of the atmosphere for cosmic-ray protons in the kinetic energy range 0.2–160more » GeV and helium nuclei in the range 0.15–80 GeV/nucleon. The corresponding magnetic-rigidity ranges are 0.6–160 GV for protons and 1.1–160 GV for helium. These spectra are compared to measurements from previous BESS flights and from ATIC-2, PAMELA, and AMS-02. We also report the ratio of the proton and helium fluxes from 1.1 to 160 GV and compare this to the ratios from PAMELA and AMS-02.« less

Novel insights into the bioenergetics of mixed-acid fermentation: can hydrogen and proton cycles combine to help maintain a proton motive force?

PubMed

Trchounian, Armen; Gary Sawers, R

2014-01-01

Escherichia coli possesses four [NiFe]-hydrogenases that catalyze the reversible redox reaction of 2H(+) + 2e(-) ↔ H2. These enzymes together have the potential to form a hydrogen cycle across the membrane. Their activity, operational direction, and interaction with each other depend on the fermentation substrate and particularly pH. The enzymes producing H2 are likely able to translocate protons through the membrane. Moreover, the activity of some of these enzymes is dependent on the F0 F1 -ATPase, thus linking a proton cycle with the cycling of hydrogen. These two cycles are suggested to have a primary basic role in modulating the cell's energetics during mixed-acid fermentation, particularly in response to pH. Nevertheless, the mechanisms underlying the physical interactions between these enzyme complexes, as well as how this is controlled, are still not clearly understood. Here, we present a synopsis of the potential impact of proton-hydrogen cycling in fermentative bioenergetics. © 2013 International Union of Biochemistry and Molecular Biology.

Designing a range modulator wheel to spread-out the Bragg peak for a passive proton therapy facility

NASA Astrophysics Data System (ADS)

Jia, S. Bijan; Romano, F.; Cirrone, Giuseppe A. P.; Cuttone, G.; Hadizadeh, M. H.; Mowlavi, A. A.; Raffaele, L.

2016-01-01

In proton beam therapy, a Spread-Out Bragg peak (SOBP) is used to establish a uniform dose distribution in the target volume. In order to create a SOBP, several Bragg peaks of different ranges, corresponding to different entrance energies, with certain intensities (weights) should be combined each other. In a passive beam scattering system, the beam is usually extracted from a cyclotron at a constant energy throughout a treatment. Therefore, a SOBP is produced by a range modulator wheel, which is basically a rotating wheel with steps of variable thicknesses, or by using the ridge filters. In this study, we used the Geant4 toolkit to simulate a typical passive scattering beam line. In particular, the CATANA transport beam line of INFN Laboratori Nazionali del Sud (LNS) in Catania has been reproduced in this work. Some initial properties of the entrance beam have been checked by benchmarking simulations with experimental data. A class dedicated to the simulation of the wheel modulators has been implemented. It has been designed in order to be easily modified for simulating any desired modulator wheel and, hence, any suitable beam modulation. By using some auxiliary range-shifters, a set of pristine Bragg peaks was obtained from the simulations. A mathematical algorithm was developed, using the simulated pristine dose profiles as its input, to calculate the weight of each pristine peak, reproduce the SOBP, and finally generate a flat dose distribution. Therefore, once the designed modulator has been realized, it has been tested at CATANA facility, comparing the experimental data with the simulation results.

Dosimetric study of uniform scanning proton therapy planning for prostate cancer patients with a metal hip prosthesis, and comparison with volumetric‐modulated arc therapy

PubMed Central

Cheng, ChihYao; Zheng, Yuanshui; Hsi, Wen; Zeidan, Omar; Schreuder, Niek; Vargas, Carlos; Larson, Gary

2014-01-01

The main purposes of this study were to 1) investigate the dosimetric quality of uniform scanning proton therapy planning (USPT) for prostate cancer patients with a metal hip prosthesis, and 2) compare the dosimetric results of USPT with that of volumetric‐modulated arc therapy (VMAT). Proton plans for prostate cancer (four cases) were generated in XiO treatment planning system (TPS). The beam arrangement in each proton plan consisted of three fields (two oblique fields and one lateral or slightly angled field), and the proton beams passing through a metal hip prosthesis was avoided. Dose calculations in proton plans were performed using the pencil beam algorithm. From each proton plan, planning target volume (PTV) coverage value (i.e., relative volume of the PTV receiving the prescription dose of 79.2 CGE) was recorded. The VMAT prostate planning was done using two arcs in the Eclipse TPS utilizing 6 MV X‐rays, and beam entrance through metallic hip prosthesis was avoided. Dose computation in the VMAT plans was done using anisotropic analytical algorithm, and calculated VMAT plans were then normalized such that the PTV coverage in the VMAT plan was the same as in the proton plan of the corresponding case. The dose‐volume histograms of calculated treatment plans were used to evaluate the dosimetric quality of USPT and VMAT. In comparison to the proton plans, on average, the maximum and mean doses to the PTV were higher in the VMAT plans by 1.4% and 0.5%, respectively, whereas the minimum PTV dose was lower in the VMAT plans by 3.4%. The proton plans had lower (or better) average homogeneity index (HI) of 0.03 compared to the one for VMAT (HI = 0.04). The relative rectal volume exposed to radiation was lower in the proton plan, with an average absolute difference ranging from 0.1% to 32.6%. In contrast, using proton planning, the relative bladder volume exposed to radiation was higher at high‐dose region with an average absolute difference ranging from 0.4% to 0.8%, and lower at low‐ and medium‐dose regions with an average absolute difference ranging from 2.7% to 10.1%. The average mean dose to the rectum and bladder was lower in the proton plans by 45.1% and 22.0%, respectively, whereas the mean dose to femoral head was lower in VMAT plans by an average difference of 79.6%. In comparison to the VMAT, the proton planning produced lower equivalent uniform dose (EUD) for the rectum (43.7 CGE vs. 51.4 Gy) and higher EUD for the femoral head (16.7 CGE vs. 9.5 Gy), whereas both the VMAT and proton planning produced comparable EUDs for the prostate tumor (76.2 CGE vs. 76.8 Gy) and bladder (50.3 CGE vs. 51.1 Gy). The results presented in this study show that the combination of lateral and oblique fields in USPT planning could potentially provide dosimetric advantage over the VMAT for prostate cancer involving a metallic hip prosthesis. PACS number: 87.55.D‐, 87.55.ne, 87.55.dk PMID:24892333

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richter, H.T.; Brown, L.S.; Lanyi, J.K.

Because asp-85 is the acceptor of the retinal Schiff base proton during light-driven proton transport by bacteriorhodopsin, modulation of its pK{sub a} in the photocycle is to be expected. The complex titration of asp-85 in the unphotolyzed protein was suggested to reflect the dependence of this residue on the protonation state of another, unidentified group. from the pH dependencies of the rate constant for the thermal equilibration of retinal isomeric states (dark adaptation) and the deprotonation kinetics of the Schiff base during the photocycle in the E204Q and E204D mutants, we identify the residue as glu-204. The nature of itsmore » interaction with our recent finding that glu-204 is the origin of the proton released to the extracellular surface upon protonation of asp-85 during that transport. We propose, therefore, that the following series of events occur in the photocycle. Protonation of asp-85 in the proton equilibrium with the Schiff base of the photoisomerized retinal results in the dissociation of glu-204 and proton release to the extracellular surface upon protonation of asp-85 during the transport. We propose, therefore, that the following series of events occur in the photocycle. Protonation of asp-85 in the proton equilibrium with the Schiff base shifts toward complete proton transfer. This constitutes the first phase of the reprotonation switch because it excludes asp-85 as a donor in the reprotonation of the Schiff base that follows. The sequential structural changes of the protein that ensue, detected earlier by diffraction, are suggested to facilitate the change of the access of the Schiff base toward the cytoplasmic side at the second phase of the switch, and the lowering the pK{sub a} of asp-96, so as to make it a proton donor, as the third phase. 77 refs., 6 figs.« less

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites.

PubMed

Kainz, Kristofer; Firat, Selim; Wilson, J Frank; Schultz, Christopher; Siker, Malika; Wang, Andrew; Olson, Dan; Li, X Allen

2015-03-21

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.

The influence of nonstationarity of the solar activity and general solar field on modulation of cosmic rays

NASA Technical Reports Server (NTRS)

Zusmanovich, A. G.; Kryakunova, O. N.; Churunova, L. F.; Shvartsman, Y. E.

1985-01-01

A numerical model of the propagation of galactic cosmic rays in interplanetary space was constructed for the case when the modulation depth determined by the level of solar activity changed in time. Also the contribution of particle drift in the regular field was calculated, and the agreement with experimental data concerning the ratio of protons and electrons in two solar activity minima is shown.

International Space Station (ISS)

NASA Image and Video Library

1999-01-01

The International Space Station (ISS) is an unparalleled international scientific and technological cooperative venture that will usher in a new era of human space exploration and research and provide benefits to people on Earth. On-Orbit assembly began on November 20, 1998, with the launch of the first ISS component, Zarya, on a Russian Proton rocket. The Space Shuttle followed on December 4, 1998, carrying the U.S.-built Unity cornecting Module. Sixteen nations are participating in the ISS program: the United States, Canada, Japan, Russia, Brazil, Belgium, Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. The ISS will include six laboratories and be four times larger and more capable than any previous space station. The United States provides two laboratories (United States Laboratory and Centrifuge Accommodation Module) and a habitation module. There will be two Russian research modules, one Japanese laboratory, referred to as the Japanese Experiment Module (JEM), and one European Space Agency (ESA) laboratory called the Columbus Orbital Facility (COF). The station's internal volume will be roughly equivalent to the passenger cabin volume of two 747 jets. Over five years, a total of more than 40 space flights by at least three different vehicles - the Space Shuttle, the Russian Proton Rocket, and the Russian Soyuz rocket - will bring together more than 100 different station components and the ISS crew. Astronauts will perform many spacewalks and use new robotics and other technologies to assemble ISS components in space.

International Space Station Assembly

NASA Technical Reports Server (NTRS)

1999-01-01

The International Space Station (ISS) is an unparalleled international scientific and technological cooperative venture that will usher in a new era of human space exploration and research and provide benefits to people on Earth. On-Orbit assembly began on November 20, 1998, with the launch of the first ISS component, Zarya, on a Russian Proton rocket. The Space Shuttle followed on December 4, 1998, carrying the U.S.-built Unity cornecting Module. Sixteen nations are participating in the ISS program: the United States, Canada, Japan, Russia, Brazil, Belgium, Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. The ISS will include six laboratories and be four times larger and more capable than any previous space station. The United States provides two laboratories (United States Laboratory and Centrifuge Accommodation Module) and a habitation module. There will be two Russian research modules, one Japanese laboratory, referred to as the Japanese Experiment Module (JEM), and one European Space Agency (ESA) laboratory called the Columbus Orbital Facility (COF). The station's internal volume will be roughly equivalent to the passenger cabin volume of two 747 jets. Over five years, a total of more than 40 space flights by at least three different vehicles - the Space Shuttle, the Russian Proton Rocket, and the Russian Soyuz rocket - will bring together more than 100 different station components and the ISS crew. Astronauts will perform many spacewalks and use new robotics and other technologies to assemble ISS components in space.

SU-E-T-138: Dosimetric Verification For Volumetric Modulated Arc Therapy Cranio-Spinal Irradiation Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goksel, E; Bilge, H; Yildiz, Yarar

2014-06-01

Purpose: Dosimetric feasibility of cranio-spinal irradiation with volumetric modulated arc therapy (VMAT-CSI) technique in terms of dose distribution accuracy was investigated using a humanlike phantom. Methods: The OARs and PTV volumes for the Rando phantom were generated on supine CT images. Eclipse (version 8.6) TPS with AAA algorithm was used to create the treatment plan with VMAT-CSI technique. RapidArc plan consisted of cranial, upper spinal (US) and lower spinal (LS) regions that were optimized in the same plan. US field was overlapped by 3cm with cranial and LS fields. Three partial arcs for cranium and 1 full arc for eachmore » US and LS region were used. The VMAT-CSI dose distribution inside the Rando phantom was measured with thermoluminescent detectors (TLD) and film dosimetry, and was compared to the calculated doses of field junctions, target and OARs. TLDs were placed at 24 positions throughout the phantom. The measured TLD doses were compared to the calculated point doses. Planar doses for field junctions were verified with Gafchromic films. Films were analyzed in PTW Verisoft application software using gamma analysis method with the 4 mm distance to agreement (DTA) and 4% dose agreement criteria. Results: TLD readings demonstrated accurate dose delivery, with a median dose difference of -0.3% (range: -8% and 12%) when compared with calculated doses for the areas inside the treatment portal. The maximum dose difference was 12% higher in testicals that are outside the treatment region and 8% lower in lungs where the heterogeinity was higher. All planar dose verifications for field junctions passed the gamma analysis and measured planar dose distributions demonstrated average 97% agreement with calculated doses. Conclusion: The dosimetric data verified with TLD and film dosimetry shows that VMAT-CSI technique provides accurate dose distribution and can be delivered safely.« less

Kilovoltage Intrafraction Monitoring for Prostate Intensity Modulated Arc Therapy: First Clinical Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Jin Aun; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales; Booth, Jeremy T.

2012-12-01

Purpose: Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials: Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiringmore » kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced {>=}3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results: KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of {>=}3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions: KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.« less

SU-E-T-29: A Dosimetric Study of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, T; Lin, X; Yin, Y

Purpose: To compare the dosimetric differences among fixed field intensity-modulated radiotherapy (IMRT) and double-arc volumetricmodulated arc therapy (VMAT) plans with simultaneous integrated boost in rectal cancer. Methods: Ten patients with rectal cancer previously treated with IMRT were included in this analysis. For each patient, two treatment techniques were designed for each patient: the fixed 7 fields IMRT and double-arc VMAT with RapidArc technique. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB). The prescribed doses to the planning target volume of the subclinical disease (PTV1) and the gross disease (PTV2) were 45 Gy andmore » 55 Gy in 25 fractions, respectively. The dose distribution in the target, the dose to the organs at risk, total MU and the delivery time in two techniques were compared to explore the dosimetric differences. Results: For the target dose and homogeneity in PTV1 and PTV2, no statistically differences were observed in the two plans. VMAT plans showed a better conformity in PTV1. VMAT plans reduced the mean dose to bladder, small bowel, femur heads and iliac wings. For iliac wings, VMAT plans resulted in a statistically significant reduction in irradiated volume of 15 Gy, 20 Gy, 30 Gy but increased the 10 Gy irradiated volume. VMAT plans reduced the small bowel irradiated volume of 20 Gy and 30 Gy. Compared with IMRT plans, VMAT plans showed a significant reduction of monitor units by nearly 30% and reduced treatment time by an average of 70% Conclusion: Compared to IMRT plans, VMAT plans showed the similar target dose and reduced the dose of the organs at risk, especially for small bowel and iliac wings. For rectal cancer, VMAT with simultaneous integrated boost can be carried out with high quality and efficiency.« less

4D dose calculation and delivery with interplay effects between respiratory motion and uniform scanning proton beam

NASA Astrophysics Data System (ADS)

Zhao, Qingya

2011-12-01

Proton radiotherapy has advantages to deliver accurate high conformal radiation dose to the tumor while sparing the surrounding healthy tissue and critical structures. However, the treatment effectiveness is degraded greatly due to patient free breathing during treatment delivery. Motion compensation for proton radiotherapy is especially challenging as proton beam is more sensitive to the density change along the beam path. Tumor respiratory motion during treatment delivery will affect the proton dose distribution and the selection of optimized parameters for treatment planning, which has not been fully addressed yet in the existing approaches for proton dose calculation. The purpose of this dissertation is to develop an approach for more accurate dose delivery to a moving tumor in proton radiotherapy, i.e., 4D proton dose calculation and delivery, for the uniform scanning proton beam. A three-step approach has been carried out to achieve this goal. First, a solution for the proton output factor calculation which will convert the prescribed dose to machine deliverable monitor unit for proton dose delivery has been proposed and implemented. The novel sector integration method is accurate and time saving, which considers the various beam scanning patterns and treatment field parameters, such as aperture shape, aperture size, measuring position, beam range, and beam modulation. Second, tumor respiratory motion behavior has been statistically characterized and the results have been applied to advanced image guided radiation treatment. Different statistical analysis and correlation discovery approaches have been investigated. The internal / external motion correlation patterns have been simulated, analyzed, and applied in a new hybrid gated treatment to improve the target coverage. Third, a dose calculation method has been developed for 4D proton treatment planning which integrates the interplay effects of tumor respiratory motion patterns and proton beam delivery mechanism. These three steps provide an innovative integrated framework for accurate 4D proton dose calculation and treatment planning for a moving tumor, which extends the functionalities of existing 3D planning systems. In short, this dissertation work addresses a few important problems for effective proton radiotherapy to a moving target. The outcomes of the dissertation are very useful for motion compensation with advanced image guided proton treatment.

[Dosimetric comparing between protons beam and photons beam
for lung cancer radiotherapy: a meta-analysis].

PubMed

Tian, Guangwei; Li, Nan; Li, Guang

2013-05-01

The clinical evidences are not sufficient on the proton beam therapy of lung cancer for lacking of the RCTs on the comparing the proton with the photon beam in lung cancer radiotherapy. The aim of this study is to evaluate the dosimetry superiority of the proton beam and provide more valuable evidences to the clinical researches. Clinical trails of dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy were obtained from the Cochrane library, Pubmed, EMbase, CBM, CNKI, VIP, and Wan Fang databases. The data included in the study were evaluated and analyzed using the Cochrane Collaboration's RevMan 5.2 software. Six trails were included. Compared to photon therapy (three-dimensional conformal photon radiotherapy, 3D-CRT), the proton therapy had a significantly lower total lung Dmean (MD=-4.15, 95%CI: -5.56--2.74, P<0.001) and V20, V10, V5 (MD=-10.92, 95%CI: -13.23--8.62, P<0.001); The V20, V10, V5 significantly decreased in proton therapy group. Compared to photon therapy (intensity-modulated photon radiotherapy, IMRT), V20, V10, V5 were also significantly lowered in proton therapy group (MD=-3.70, 95%CI: -5.31--2.10, P<0.001; MD=-8.86, 95%CI: -10.74--6.98, P<0.001; MD=-20.13, 95%CI: -27.11--13.14, P<0.001); The esophagus Dmean was not lowered, while the heart Dmean decreased in proton therapy group. Comparing to photon beam radiotherapy (3D-CRT and IMRT), proton beam therapy is advantageous in dosimetry of the lung cancer radiotherapy and recommended for clinical applying.

Beam test of CSES silicon strip detector module

NASA Astrophysics Data System (ADS)

Zhang, Da-Li; Lu, Hong; Wang, Huan-Yu; Li, Xin-Qiao; Xu, Yan-Bing; An, Zheng-Hua; Yu, Xiao-xia; Wang, Hui; Shi, Feng; Wang, Ping; Zhao, Xiao-Yun

2017-05-01

The silicon-strip tracker of the China Seismo-Electromagnetic Satellite (CSES) consists of two double-sided silicon strip detectors (DSSDs) which provide incident particle tracking information. A low-noise analog ASIC VA140 was used in this study for DSSD signal readout. A beam test on the DSSD module was performed at the Beijing Test Beam Facility of the Beijing Electron Positron Collider (BEPC) using a 400-800 MeV/c proton beam. The pedestal analysis results, RMSE noise, gain correction, and intensity distribution of incident particles of the DSSD module are presented. Supported by the XXX Civil Space Programme

Controlling laser driven protons acceleration using a deformable mirror at a high repetition rate

NASA Astrophysics Data System (ADS)

Noaman-ul-Haq, M.; Sokollik, T.; Ahmed, H.; Braenzel, J.; Ehrentraut, L.; Mirzaie, M.; Yu, L.-L.; Sheng, Z. M.; Chen, L. M.; Schnürer, M.; Zhang, J.

2018-03-01

We present results from a proof-of-principle experiment to optimize laser driven protons acceleration by directly feeding back its spectral information to a deformable mirror (DM) controlled by evolutionary algorithms (EAs). By irradiating a stable high-repetition rate tape driven target with ultra-intense pulses of intensities ∼1020 W/ cm2, we optimize the maximum energy of the accelerated protons with a stability of less than ∼5% fluctuations near optimum value. Moreover, due to spatio-temporal development of the sheath field, modulations in the spectrum are also observed. Particularly, a prominent narrow peak is observed with a spread of ∼15% (FWHM) at low energy part of the spectrum. These results are helpful to develop high repetition rate optimization techniques required for laser-driven ion accelerators.

2J, 3J-HMBC: A New Long-Range Heteronuclear Shift Correlation Technique Capable of Differentiating 2JCH from 3JCH Correlations to Protonated Carbons

NASA Astrophysics Data System (ADS)

Krishnamurthy, V. V.; Russell, David J.; Hadden, Chad E.; Martin, Gary E.

2000-09-01

The development of a series of new, accordion-optimized long-range heteronuclear shift correlation techniques has been reported. A further derivative of the constant time variable delay introduced in the IMPEACH-MBC experiment, a STAR (Selectively Tailored Accordion F1 Refocusing) operator is described in the present report. Incorporation of the STAR operator with the capability of user-selected homonuclear modulation scaling as in the CIGAR-HMBC experiment, into a long-range heteronuclear shift correlation pulse sequence, 2J,3J-HMBC, affords for the first time in a proton-detected experiment the means of unequivocally differentiating two-bond (2JCH) from three-bond (3JCH) long-range correlations to protonated carbons.

Proposed linear energy transfer areal detector for protons using radiochromic film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, Rulon; Lin, Liyong; Fager, Marcus

2015-04-15

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured atmore » a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%–10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%–15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.« less

A fast optimization algorithm for multicriteria intensity modulated proton therapy planning.

PubMed

Chen, Wei; Craft, David; Madden, Thomas M; Zhang, Kewu; Kooy, Hanne M; Herman, Gabor T

2010-09-01

To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK'S interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

Characterization of >100 T magnetic fields associated with relativistic Weibel instability in laser-produced plasmas

NASA Astrophysics Data System (ADS)

Mishra, Rohini; Ruyer, Charles; Goede, Sebastian; Roedel, Christian; Gauthier, Maxence; Zeil, Karl; Schramm, Ulrich; Glenzer, Siegfried; Fiuza, Frederico

2016-10-01

Weibel-type instabilities can occur in weakly magnetized and anisotropic plasmas of relevance to a wide range of astrophysical and laboratory scenarios. It leads to the conversion of a significant fraction of the kinetic energy of the plasma into magnetic energy. We will present a detailed numerical study, using 2D and 3D PIC simulations of the Weibel instability in relativistic laser-solid interactions. In this case, the instability develops due to the counter-streaming of laser-heated electrons and the background return current. We show that the growth rate of the instability is maximized near the critical density region on the rear side of the expanded plasma, producing up to 400 MG magnetic fields for Hydrogen plasmas. We have found that this strong field can be directly probed by energetic protons accelerated in rear side of the plasma by Target Normal Sheath Acceleration (TNSA). This allows the experimental characterization of the instability from the analysis of the spatial modulation of the detected protons. Our numerical results are compared with recent laser experiments with Hydrogen jets and show good agreement with the proton modulations observed experimentally. This work was supported by the DOE Office of Science, Fusion Energy Science (FWP 100182).

Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study

NASA Astrophysics Data System (ADS)

Yepes, Pablo P.; Eley, John G.; Liu, Amy; Mirkovic, Dragan; Randeniya, Sharmalee; Titt, Uwe; Mohan, Radhe

2016-04-01

Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC. In this study, we present the validation of an efficient dose calculation algorithm for intensity modulated proton therapy, the fast dose calculator (FDC), based on a track-repeating technique. We validated the FDC algorithm for 23 patients, which included 7 brain, 6 head-and-neck, 5 lung, 1 spine, 1 pelvis and 3 prostate cases. For validation, we compared FDC-generated dose distributions with those from a full-fledged Monte Carlo based on GEANT4 (G4). We compared dose-volume-histograms, 3D-gamma-indices and analyzed a series of dosimetric indices. More than 99% of the voxels in the voxelized phantoms describing the patients have a gamma-index smaller than unity for the 2%/2 mm criteria. In addition the difference relative to the prescribed dose between the dosimetric indices calculated with FDC and G4 is less than 1%. FDC reduces the calculation times from 5 ms per proton to around 5 μs.

Development of the integrated control system for the microwave ion source of the PEFP 100-MeV proton accelerator

NASA Astrophysics Data System (ADS)

Song, Young-Gi; Seol, Kyung-Tae; Jang, Ji-Ho; Kwon, Hyeok-Jung; Cho, Yong-Sub

2012-07-01

The Proton Engineering Frontier Project (PEFP) 20-MeV proton linear accelerator is currently operating at the Korea Atomic Energy Research Institute (KAERI). The ion source of the 100-MeV proton linac needs at least a 100-hour operation time. To meet the goal, we have developed a microwave ion source that uses no filament. For the ion source, a remote control system has been developed by using experimental physics and the industrial control system (EPICS) software framework. The control system consists of a versa module europa (VME) and EPICS-based embedded applications running on a VxWorks real-time operating system. The main purpose of the control system is to control and monitor the operational variables of the components remotely and to protect operators from radiation exposure and the components from critical problems during beam extraction. We successfully performed the operation test of the control system to confirm the degree of safety during the hardware performance.

Research activities at the Loma Linda University and Proton Treatment Facility--an overview

NASA Technical Reports Server (NTRS)

Nelson, G. A.; Green, L. M.; Gridley, D. S.; Archambeau, J. O.; Slater, J. M.

2001-01-01

The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion-irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation.

Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study

PubMed Central

Mori, Yoshikazu; Ogawa, Kazuo; Warabi, Eiji; Yamamoto, Masahiro; Hirokawa, Takatsugu

2016-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity. The detailed binding mode of each ligand was then simulated by computational analysis. As a result, three amino acids (L518, F591 and L670) were newly identified as being involved in ligand binding and/or modulation of proton sensitivity. In addition, in silico docking simulation and a subsequent mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in a unique manner. These results provide novel insights into the binding mode of various vanilloids to the channel and will be helpful in developing a TRPV1 modulator. PMID:27606946

Modulation of p-Cyanophenylalanine Fluorescence by Amino Acid Side-chains and Rational Design of Fluorescence Probes of α-Helix Formation

PubMed Central

Taskent-Sezgin, Humeyra; Marek, Peter; Thomas, Rosanne; Goldberg, Daniel; Chung, Juah; Carrico, Isaac; Raleigh, Daniel P.

2011-01-01

p-Cyanophenylalanine is an extremely useful fluorescence probe of protein structure which can be recombinantly and chemically incorporated into proteins. The probe has been used to study protein folding, protein-membrane interactions, protein-peptide interactions and amyloid formation, however the factors that control its fluorescence are not fully understood. Hydrogen bonding to the cyano group is known to play a major role in modulating the fluorescence quantum yield, but the role of potential side-chain quenchers has not yet been elucidated. A systematic study on the effects of different side-chains on p-cyanophenylalanine fluorescence is reported. Tyr is found to have the largest effect followed by deprotonated His, Met, Cys, protonated His, Asn, Arg, and protonated Lys. Deprotonated amino groups are much more effective fluorescence quenchers than protonated amino groups. Free neutral imidazole and hydroxide ion are also effective quenchers of p-cyanophenylalanine fluorescence with Stern-Volmer constants of 39.8 M−1 and 22.1 M−1, respectively. The quenching of p-cyanophenylalanine fluorescence by specific side-chains is exploited to develop specific, high sensitivity, fluorescence probes of helix formation. The approach is demonstrated with Ala based peptides that contain a p-cyanophenylalanine-His or a p-cyanophenylalanine-Tyr pair located at positions i and i+4. The p-cyanophenylalanine-His pair is most useful when the His side-chain is deprotonated and is, thus, complimentary to Trp-His pair which is most sensitive when the His side-chain is protonated. PMID:20565125

ROLE OF THE CORONAL ALFVÉN SPEED IN MODULATING THE SOLAR-WIND HELIUM ABUNDANCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Y.-M., E-mail: yi.wang@nrl.navy.mil

The helium abundance He/H in the solar wind is relatively constant at ∼0.04 in high-speed streams, but varies in phase with the sunspot number in slow wind, from ∼0.01 at solar minimum to ∼0.04 at maximum. Suggested mechanisms for helium fractionation have included frictional coupling to protons and resonant interactions with high-frequency Alfvénic fluctuations. We compare He/H measurements during 1995–2015 with coronal parameters derived from source-surface extrapolations of photospheric field maps. We find that the near-Earth helium abundance is an increasing function of the magnetic field strength and Alfvén speed v {sub A} in the outer corona, while being onlymore » weakly correlated with the proton flux density. Throughout the solar cycle, fast wind is associated with short-term increases in v {sub A} near the source surface; resonance with Alfvén waves, with v {sub A} and the relative speed of α -particles and protons decreasing with increasing heliocentric distance, may then lead to enhanced He/H at 1 au. The modulation of helium in slow wind reflects the tendency for the associated coronal Alfvén speeds to rise steeply from sunspot minimum, when this wind is concentrated around the source-surface neutral line, to sunspot maximum, when the source-surface field attains its peak strengths. The helium abundance near the source surface may represent a balance between collisional decoupling from protons and Alfvén wave acceleration.« less

A light-powered bio-capacitor with nanochannel modulation.

PubMed

Rao, Siyuan; Lu, Shanfu; Guo, Zhibin; Li, Yuan; Chen, Deliang; Xiang, Yan

2014-09-03

An artificial bio-capacitor system is established, consisting of the proton-pump protein proteorhodopsin and a modified alumina nanochannel, inspired by the capacitor-like behavior of plasma membranes realized through the cooperation of ion-pump and ion-channel proteins. Capacitor-like features of this simplified system are realized and identified, and the photocurrent duration time can be modulated by nanochannel modification to obtain favorable square-wave currents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trimming algorithm of frequency modulation for CIAE-230 MeV proton superconducting synchrocyclotron model cavity

NASA Astrophysics Data System (ADS)

Li, Pengzhan; Zhang, Tianjue; Ji, Bin; Hou, Shigang; Guo, Juanjuan; Yin, Meng; Xing, Jiansheng; Lv, Yinlong; Guan, Fengping; Lin, Jun

2017-01-01

A new project, the 230 MeV proton superconducting synchrocyclotron for cancer therapy, was proposed at CIAE in 2013. A model cavity is designed to verify the frequency modulation trimming algorithm featuring a half-wave structure and eight sets of rotating blades for 1 kHz frequency modulation. Based on the electromagnetic (EM) field distribution analysis of the model cavity, the variable capacitor works as a function of time and the frequency can be written in Maclaurin series. Curve fitting is applied for theoretical frequency and original simulation frequency. The second-order fitting excels at the approximation given its minimum variance. Constant equivalent inductance is considered as an important condition in the calculation. The equivalent parameters of theoretical frequency can be achieved through this conversion. Then the trimming formula for rotor blade outer radius is found by discretization in time domain. Simulation verification has been performed and the results show that the calculation radius with minus 0.012 m yields an acceptable result. The trimming amendment in the time range of 0.328-0.4 ms helps to reduce the frequency error to 0.69% in Simulation C with an increment of 0.075 mm/0.001 ms, which is half of the error in Simulation A (constant radius in 0.328-0.4 ms). The verification confirms the feasibility of the trimming algorithm for synchrocyclotron frequency modulation.

Critical appraisal of RapidArc radiosurgery with flattening filter free photon beams for benign brain lesions in comparison to GammaKnife: a treatment planning study

PubMed Central

2014-01-01

Background To evaluate the role of RapidArc (RA) for stereotactic radiosurgery (SRS) of benign brain lesions in comparison to GammaKnife (GK) based technique. Methods Twelve patients with vestibular schwannoma (VS, n = 6) or cavernous sinus meningioma (CSM, n = 6) were planned for both SRS using volumetric modulated arc therapy (VMAT) by RA. 104 MV flattening filter free photon beams with a maximum dose rate of 2400 MU/min were selected. Data were compared against plans optimised for GK. A single dose of 12.5 Gy was prescribed. The primary objective was to assess treatment plan quality. Secondary aim was to appraise treatment efficiency. Results For VS, comparing best GK vs. RA plans, homogeneity was 51.7 ± 3.5 vs. 6.4 ± 1.5%; Paddick conformity Index (PCI) resulted 0.81 ± 0.03 vs. 0.84 ± 0.04. Gradient index (PGI) was 2.7 ± 0.2 vs. 3.8 ± 0.6. Mean target dose was 17.1 ± 0.9 vs. 12.9 ± 0.1 Gy. For the brain stem, D1cm3 was 5.1 ± 2.0 Gy vs 4.8 ± 1.6 Gy. For the ipsilateral cochlea, D0.1cm3 was 1.7 ± 1.0 Gy vs. 1.8 ± 0.5 Gy. For CSM, homogeneity was 52.3 ± 2.4 vs. 12.4 ± 0.6; PCI: 0.86 ± 0.05 vs. 0.88 ± 0.05; PGI: 2.6 ± 0.1 vs. 3.8 ± 0.5; D1cm3 to brain stem was 5.4 ± 2.8 Gy vs. 5.2 ± 2.8 Gy; D0.1cm3 to ipsi-lateral optic nerve was 4.2 ± 2.1 vs. 2.1 ± 1.5 Gy; D0.1cm3 to optic chiasm was 5.9 ± 3.1 vs. 4.5 ± 2.1 Gy. Treatment time was 53.7 ± 5.8 (64.9 ± 24.3) minutes for GK and 4.8 ± 1.3 (5.0 ± 0.7) minutes for RA for schwannomas (meningiomas). Conclusions SRS with RA and FFF beams revealed to be adequate and comparable to GK in terms of target coverage, homogeneity, organs at risk sparing with some gain in terms of treatment efficiency. PMID:24884967

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Samantha, E-mail: samantha.warren@oncology.ox.ac.uk; Partridge, Mike; Bolsi, Alessandra

Purpose: Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods andmore » Materials: For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV){sub 50Gy} or PTV{sub 62.5Gy} (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results: SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D{sub 98} was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D{sub 98} was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D{sub 98} was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D{sub 98} was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions: The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial.« less

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

PubMed Central

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J.; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

2016-01-01

Purpose Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods and Materials For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. PMID:27084641

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning.

PubMed

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A

2016-05-01

Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-T-146: Reference Dosimetry for Protons and Light-Ion Beams Based on Graphite Calorimetry.

PubMed

Rossomme, S; Palmans, H; Thomas, R; Lee, N; Bailey, M; Shipley, D; Al-Sulaiti, L; Cirrone, P; Romano, F; Kacperek, A; Bertrand, D; Vynckier, S

2012-06-01

The IAEA TRS-398 code of practice can be applied for the measurement of absorbed dose to water under reference conditions with an ionization chamber. For protons, the combined relative standard uncertainty on those measurements is less than 2% while for light-ion beams, it is considerably larger, i.e. 3.2%, mainly due to the higher uncertainty contributions for the water to air stopping power ration and the W air-value on the beam quality correction factors kQ,Q 0 . To decrease this uncertainty, a quantification of kQ,Q 0 is proposed using a primary standard level graphite calorimeter. This work includes numerical and experimental determinations of dose conversion factors to derive dose to water from graphite calorimetry. It also reports on the first experimental data obtained with the graphite calorimeter in proton, alpha and carbon ion beams. Firstly, the dose conversion has been calculated with by Geant4 Monte-Carlo simulations through the determination of the water to graphite stopping power ratio and the fluence correction factor. The latter factor was also derived by comparison of measured ionization curves in graphite and water. Secondly, kQ,Q 0 was obtained by comparison of the dose response of ionization chambers with that of the calorimeter. Stopping power ratios are found to vary by no more than 0.35% up to the Bragg peak, while fluence correction factors are shown to increase slightly above unity close to the Bragg peak. The comparison of the calorimeter with ionization chambers is currently under analysis. For the modulated proton beam, preliminary results on W air confirm the value recommended in TRS-398. Data in both the non-modulated proton and light-ion beams indicate higher values but further investigation of heat loss corrections is needed. The application of graphite calorimetry to proton, alpha and carbon ion beams has been demonstrated successfully. Other experimental campaigns will be held in 2012. This work is supported by the BioWin program of the Wallon Government. © 2012 American Association of Physicists in Medicine.

Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

NASA Astrophysics Data System (ADS)

Fontenot, Jonas David

External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only weakly on uncertainties in the risk model and inter-patient variations. Second cancer risks were sensitive to changes in the RBE of neutrons. However, the findings of the study were qualitatively consistent for all patient sizes and risk models considered, and for all neutron RBE values less than 100.

SU-F-T-116: Predicting IQ and the Risk of Hearing Loss Following Proton Versus Photon Radiotherapy for Pediatric Brain Tumor Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortin, D; Sharpe, M; Laperriere, N

Purpose: The increased sparing of normal tissues in intensity modulated proton therapy (IMPT) compared to photon intensity modulated radiotherapy (IMRT) in brain tumor treatments should translate into improved neurocognitive outcomes. Models were used to estimate the intelligence quotient (IQ) and the risk of hearing loss 5 years post radiotherapy and to compare outcomes of proton against photon in pediatric brain tumors. Methods: Patients who had received radical IMRT were randomly selected from our retrospective database: 10 cases each of craniopharyngioma, ependymoma and medulloblastoma, and 20 cases of glioma. The existing planning CT and contours were used to generate IMPT plans.more » The RBE-corrected dose to brain structures and cochleas were calculated for both IMPT and IMRT. A model was applied to estimate IQ using a Markov chain Monte Carlo technique. The reported incidence of hearing loss as a function of cochlear dose was used to estimate the rate of occurrence. Results: The average brain dose was less in all IMPT plans compared to IMRT: ranging from a 6.7% reduction (P=0.003) in the case of medulloblastoma to 38% (P=0.007) for craniopharyngioma. This dose reduction translated into a gain in IQ of 1.9 points on average for protons vs photons for the whole cohort at 5 years post-treatment (P=0.011). In terms of specific diseases, the gains in IQ ranged from 0.8 points for medulloblastoma, to 2.7 points for craniopharyngioma. Hearing loss probability was evaluated on a per-ear-basis and was found to be systematically less for proton versus photon: overall 2.9% versus 7.2% (P < 0.001). Conclusion: A novel method was developed to predict neurocognitive outcomes in pediatric brain tumor patients on a case-by-case basis. A modest gain in IQ was systematically observed for proton in all patients. Given the uncertainties within the model used and our reinterpretation, these gains may be underestimated.« less

Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Steven J., E-mail: sjfrank@mdanderson.org; Cox, James D.; Gillin, Michael

2014-07-15

Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effectmore » of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.« less

Inelastic dark matter with spin-dependent couplings to protons and large modulation fractions in DAMA

NASA Astrophysics Data System (ADS)

Scopel, Stefano; Yoon, Kook-Hyun

2016-02-01

We discuss a scenario where the DAMA modulation effect is explained by a Weakly Interacting Massive Particle (WIMP) which upscatters inelastically to a heavier state and predominantly couples to the spin of protons. In this scenario constraints from xenon and germanium targets are evaded dynamically, due to the suppression of the WIMP coupling to neutrons, while those from fluorine targets are evaded kinematically, because the minimal WIMP incoming speed required to trigger upscatters off fluorine exceeds the maximal WIMP velocity in the Galaxy, or is very close to it. In this scenario WIMP scatterings off sodium are usually sensitive to the large-speed tail of the WIMP velocity distribution and modulated fractions of the signal close to unity arise in a natural way. On the other hand, a halo-independent analysis with more conservative assumptions about the WIMP velocity distribution allows to extend the viable parameter space to configurations where large modulated fractions are not strictly necessary. We discuss large modulated fractions in the Maxwellian case showing that they imply a departure from the usual cosine time dependence of the expected signal in DAMA. However we explicitly show that the DAMA data is not sensitive to this distortion, both in time and frequency space, even in the extreme case of a 100 % modulated fraction. Moreover the same scenario provides an explanation of the maximum in the energy spectrum of the modulation amplitude detected by DAMA in terms of WIMPs whose minimal incoming speed matches the kinematic threshold for inelastic upscatters. For the elastic case the detection of such maximum suggests an inversion of the modulation phase below the present DAMA energy threshold, while this is not expected for inelastic scattering. This may allow to discriminate between the two scenarios in a future low-threshold analysis of the DAMA data.

Inelastic dark matter with spin-dependent couplings to protons and large modulation fractions in DAMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scopel, Stefano; Yoon, Kook-Hyun, E-mail: scopel@sogang.ac.kr, E-mail: koreasds@naver.com

2016-02-01

We discuss a scenario where the DAMA modulation effect is explained by a Weakly Interacting Massive Particle (WIMP) which upscatters inelastically to a heavier state and predominantly couples to the spin of protons. In this scenario constraints from xenon and germanium targets are evaded dynamically, due to the suppression of the WIMP coupling to neutrons, while those from fluorine targets are evaded kinematically, because the minimal WIMP incoming speed required to trigger upscatters off fluorine exceeds the maximal WIMP velocity in the Galaxy, or is very close to it. In this scenario WIMP scatterings off sodium are usually sensitive tomore » the large-speed tail of the WIMP velocity distribution and modulated fractions of the signal close to unity arise in a natural way. On the other hand, a halo-independent analysis with more conservative assumptions about the WIMP velocity distribution allows to extend the viable parameter space to configurations where large modulated fractions are not strictly necessary. We discuss large modulated fractions in the Maxwellian case showing that they imply a departure from the usual cosine time dependence of the expected signal in DAMA. However we explicitly show that the DAMA data is not sensitive to this distortion, both in time and frequency space, even in the extreme case of a 100 % modulated fraction. Moreover the same scenario provides an explanation of the maximum in the energy spectrum of the modulation amplitude detected by DAMA in terms of WIMPs whose minimal incoming speed matches the kinematic threshold for inelastic upscatters. For the elastic case the detection of such maximum suggests an inversion of the modulation phase below the present DAMA energy threshold, while this is not expected for inelastic scattering. This may allow to discriminate between the two scenarios in a future low-threshold analysis of the DAMA data.« less

Attempt to accelerate asymmetric species with unequal frequencies in RHIC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, C.; Luo, Y.; Marusic, A.

This report summarizes the beam studies on accelerating asymmetric beams with unequal frequencies, during the proton-Gold/Aluminum run in 2015. The experiment failed due to modulated beam-beam effects even though the beams were separated by at least 15 mm.

Gamma-ray spectrometer experiment, Apollo 17: NaI(T1) detector crystal activation

NASA Technical Reports Server (NTRS)

Trombka, J. I.; Schmadebeck, R. L.; Bielefeld, M.; Okelley, G. D.; Eldridge, J. S.; Northcutt, K. J.; Metzger, A. E.; Schonfeld, E.; Peterson, L. E.; Arnold, J. R.

1973-01-01

An attempt was made to obtain experimental data on proton induced activity and its effect on gamma ray spectral measurements. A NaI(T1) crystal flown in Apollo 17 command module was used for the experiment.

Assembling Resistive Plate Chambers for the PHENIX Detector

NASA Astrophysics Data System (ADS)

Drummond, Kirk

2009-10-01

A fast muon trigger for the Pioneering High Energy Nuclear Interaction eXperiment (PHENIX) will enable the study of flavor separated quark and anti-quark spin polarizations in the proton through the analysis of single spin asymmetries for W-boson production in proton-proton collisions. The Phenix experiment is capable of measuring high momentum muons at forward rapidity, but the current online trigger does not have sufficient rejection to sample rare leptons from W-decay at the highest luminosities at the Relativistic Heavy Ion Collider. This upgrade will enhance our ability to collect and analyze muons that decay from W-bosons produced in polarized proton-proton collisions. This upgrade is comprised of half-octants which encompass three different Resistive Plate Chamber (RPCs) modules that encase a sandwich of copper, mylar, gas gaps, and a signal plane. The summer of 2009 marked the start of this full production, with teams from many institutions contributing to the production in the assembly tent at Brookhaven National Lab. The North Arm Station 3 part of the upgrade is scheduled to be installed in the fall of 2009, and the remaining stations will be installed by the fall of 2011.

Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation.

PubMed

Tian, Jian; Zhao, WeiLing; Tian, Sisi; Slater, James M; Deng, Zhiyong; Gridley, Daila S

2011-11-01

The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.

Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

NASA Astrophysics Data System (ADS)

Islam, M. R.; Collums, T. L.; Zheng, Y.; Monson, J.; Benton, E. R.

2013-11-01

The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy-1 for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy-1 for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

NASA Astrophysics Data System (ADS)

Meyer, Juergen; Stewart, Robert D.; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-12-01

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Biological and dosimetric characterisation of spatially fractionated proton minibeams.

PubMed

Meyer, Juergen; Stewart, Robert D; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-11-21

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Voltage-gated Proton Channels

PubMed Central

DeCoursey, Thomas E.

2014-01-01

Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

Quantum entanglement and spin control in silicon nanocrystal.

PubMed

Berec, Vesna

2012-01-01

Selective coherence control and electrically mediated exchange coupling of single electron spin between triplet and singlet states using numerically derived optimal control of proton pulses is demonstrated. We obtained spatial confinement below size of the Bohr radius for proton spin chain FWHM. Precise manipulation of individual spins and polarization of electron spin states are analyzed via proton induced emission and controlled population of energy shells in pure (29)Si nanocrystal. Entangled quantum states of channeled proton trajectories are mapped in transverse and angular phase space of (29)Si <100> axial channel alignment in order to avoid transversal excitations. Proton density and proton energy as impact parameter functions are characterized in single particle density matrix via discretization of diagonal and nearest off-diagonal elements. We combined high field and low densities (1 MeV/92 nm) to create inseparable quantum state by superimposing the hyperpolarizationed proton spin chain with electron spin of (29)Si. Quantum discretization of density of states (DOS) was performed by the Monte Carlo simulation method using numerical solutions of proton equations of motion. Distribution of gaussian coherent states is obtained by continuous modulation of individual spin phase and amplitude. Obtained results allow precise engineering and faithful mapping of spin states. This would provide the effective quantum key distribution (QKD) and transmission of quantum information over remote distances between quantum memory centers for scalable quantum communication network. Furthermore, obtained results give insights in application of channeled protons subatomic microscopy as a complete versatile scanning-probe system capable of both quantum engineering of charged particle states and characterization of quantum states below diffraction limit linear and in-depth resolution.PACS NUMBERS: 03.65.Ud, 03.67.Bg, 61.85.+p, 67.30.hj.

Characteristics of trapped proton anisotropy at Space Station Freedom altitudes

NASA Technical Reports Server (NTRS)

Armstrong, T. W.; Colborn, B. L.; Watts, J. W.

1990-01-01

The ionizing radiation dose for spacecraft in low-Earth orbit (LEO) is produced mainly by protons trapped in the Earth's magnetic field. Current data bases describing this trapped radiation environment assume the protons to have an isotropic angular distribution, although the fluxes are actually highly anisotropic in LEO. The general nature of this directionality is understood theoretically and has been observed by several satellites. The anisotropy of the trapped proton exposure has not been an important practical consideration for most previous LEO missions because the random spacecraft orientation during passage through the radiation belt 'averages out' the anisotropy. Thus, in spite of the actual exposure anisotropy, cumulative radiation effects over many orbits can be predicted as if the environment were isotropic when the spacecraft orientation is variable during exposure. However, Space Station Freedom will be gravity gradient stabilized to reduce drag, and, due to this fixed orientation, the cumulative incident proton flux will remain anisotropic. The anisotropy could potentially influence several aspects of Space Station design and operation, such as the appropriate location for radiation sensitive components and experiments, location of workstations and sleeping quarters, and the design and placement of radiation monitors. Also, on-board mass could possible be utilized to counteract the anisotropy effects and reduce the dose exposure. Until recently only omnidirectional data bases for the trapped proton environment were available. However, a method to predict orbit-average, angular dependent ('vector') trapped proton flux spectra has been developed from the standard omnidirectional trapped proton data bases. This method was used to characterize the trapped proton anisotropy for the Space Station orbit (28.5 degree inclination, circular) in terms of its dependence on altitude, solar cycle modulation (solar minimum vs. solar maximum), shielding thickness, and radiation effect (silicon rad and rem dose).

Proton-pumping mechanism of cytochrome c oxidase: A kinetic master-equation approach

PubMed Central

Kim, Young C.; Hummer, Gerhard

2011-01-01

Cytochrome c oxidase (CcO) is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, CcO translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in CcO. Basic principles of the CcO proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the ative-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for CcO provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. PMID:21946020

Advances in radiotherapy techniques and delivery for non-small cell lung cancer: benefits of intensity-modulated radiation therapy, proton therapy, and stereotactic body radiation therapy

PubMed Central

Diwanji, Tejan P.; Mohindra, Pranshu; Vyfhuis, Melissa; Snider, James W.; Kalavagunta, Chaitanya; Mossahebi, Sina; Yu, Jen; Feigenberg, Steven

2017-01-01

The 21st century has seen several paradigm shifts in the treatment of non-small cell lung cancer (NSCLC) in early-stage inoperable disease, definitive locally advanced disease, and the postoperative setting. A key driver in improvement of local disease control has been the significant evolution of radiation therapy techniques in the last three decades, allowing for delivery of definitive radiation doses while limiting exposure of normal tissues. For patients with locally-advanced NSCLC, the advent of volumetric imaging techniques has allowed a shift from 2-dimensional approaches to 3-dimensional conformal radiation therapy (3DCRT). The next generation of 3DCRT, intensity-modulated radiation therapy and volumetric-modulated arc therapy (VMAT), have enabled even more conformal radiation delivery. Clinical evidence has shown that this can improve the quality of life for patients undergoing definitive management of lung cancer. In the early-stage setting, conventional fractionation led to poor outcomes. Evaluation of altered dose fractionation with the previously noted technology advances led to advent of stereotactic body radiation therapy (SBRT). This technique has dramatically improved local control and expanded treatment options for inoperable, early-stage patients. The recent development of proton therapy has opened new avenues for improving conformity and the therapeutic ratio. Evolution of newer proton therapy techniques, such as pencil-beam scanning (PBS), could improve tolerability and possibly allow reexamination of dose escalation. These new progresses, along with significant advances in systemic therapies, have improved survival for lung cancer patients across the spectrum of non-metastatic disease. They have also brought to light new challenges and avenues for further research and improvement. PMID:28529896

The regulation of the chloroplast proton motive force plays a key role for photosynthesis in fluctuating light.

PubMed

Armbruster, Ute; Correa Galvis, Viviana; Kunz, Hans-Henning; Strand, Deserah D

2017-06-01

Plants use sunlight as their primary energy source. During photosynthesis, absorbed light energy generates reducing power by driving electron transfer reactions. These are coupled to the transfer of protons into the thylakoid lumen, generating a proton motive force (pmf) required for ATP synthesis. Sudden alterations in light availability have to be met by regulatory mechanisms to avoid the over-accumulation of reactive intermediates and maximize energy efficiency. Here, the acidification of the lumen, as an intermediate product of photosynthesis, plays an important role by regulating photosynthesis in response to excitation energy levels. Recent findings reveal pmf regulation and the modulation of its composition as key determinants for efficient photosynthesis, plant growth, and survival in fluctuating light environments. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Transmission calculation and intensity suppression for a proton therapy system

NASA Astrophysics Data System (ADS)

Chen, Wei; Yang, Jun; Qin, Bin; Liang, ZhiKai; Chen, Qushan; Liu, Kaifeng; Li, Dong; Fan, Mingwu

2018-02-01

A proton therapy project HUST-PTF (HUST Proton Therapy Facility) based on a 250 MeV isochronous superconducting cyclotron is under development in Huazhong University of Science and Technology (HUST). In this paper we report the main design features of the beam line in HUST-PTF project. The energy selection system (ESS) for energy modulation is discussed in detail, including the collimators, momentum slit and transmission calculation. Due to significant difference among the transmissions of ESS for different energies, the intensity suppression scheme by defocusing beam at high energies on collimators in the beam line is proposed and discussed. Finally, the ratios of beam intensities between low and high energies are expected to be controlled within 10 to meet the clinical requirement, and the beam optics of each energy step after intensity suppression is studied respectively.

A simultaneous multi-slice selective J-resolved experiment for fully resolved scalar coupling information

NASA Astrophysics Data System (ADS)

Zeng, Qing; Lin, Liangjie; Chen, Jinyong; Lin, Yanqin; Barker, Peter B.; Chen, Zhong

2017-09-01

Proton-proton scalar coupling plays an important role in molecular structure elucidation. Many methods have been proposed for revealing scalar coupling networks involving chosen protons. However, determining all JHH values within a fully coupled network remains as a tedious process. Here, we propose a method termed as simultaneous multi-slice selective J-resolved spectroscopy (SMS-SEJRES) for simultaneously measuring JHH values out of all coupling networks in a sample within one experiment. In this work, gradient-encoded selective refocusing, PSYCHE decoupling and echo planar spectroscopic imaging (EPSI) detection module are adopted, resulting in different selective J-edited spectra extracted from different spatial positions. The proposed pulse sequence can facilitate the analysis of molecular structures. Therefore, it will interest scientists who would like to efficiently address the structural analysis of molecules.

Anesthetic diffusion through lipid membranes depends on the protonation rate.

PubMed

Pérez-Isidoro, Rosendo; Sierra-Valdez, F J; Ruiz-Suárez, J C

2014-12-18

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon.

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography.

PubMed

Wan, Qun; Parks, Jerry M; Hanson, B Leif; Fisher, Suzanne Zoe; Ostermann, Andreas; Schrader, Tobias E; Graham, David E; Coates, Leighton; Langan, Paul; Kovalevsky, Andrey

2015-10-06

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pKa values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD=pH+0.4) values. The general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pKa values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pKa of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. These findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen.

Proton Therapy At Siteman Cancer Center: The State Of The Art

NASA Astrophysics Data System (ADS)

Bloch, Charles

2011-06-01

Barnes-Jewish Hospital is on the verge of offering proton radiation therapy to its patients. Those treatments will be delivered from the first Monarch 250, a state-of-the-art cyclotron produced by Still River Systems, Inc., Littleton, MA. The accelerator is the world's first superconducting synchrocyclotron, with a field-strength of 10 tesla, providing the smallest accelerator for high-energy protons currently available. On May 14, 2010 it was announced that the first production unit had successfully extracted 250 MeV protons. That unit is scheduled for delivery to the Siteman Cancer Center, an NCI-designated Comprehensive Cancer Center at Washington University School of Medicine. At a weight of 20 tons and with a diameter of less than 2 meters the compact cyclotron will be mounted on a gantry, another first for proton therapy systems. The single-energy system includes 3 contoured scatterers and 14 different range modulators to provide 24 distinct beam delivery configurations. This allows proton fields up to 25 cm in diameter, with a maximum range from 5.5 to 32 cm and spread-out-Bragg-peak extent up to 20 cm. Monte Carlo simulations have been run using MCNPX to simulate the clinical beam properties. Those calculations have been used to commission a commercial treatment planning system prior to final clinical measurements. MCNPX was also used to calculate the neutron background generated by protons in the scattering system and patient. Additional details of the facility and current status will be presented.

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography

PubMed Central

Wan, Qun; Parks, Jerry M.; Hanson, B. Leif; Fisher, Suzanne Zoe; Ostermann, Andreas; Schrader, Tobias E.; Graham, David E.; Coates, Leighton; Langan, Paul; Kovalevsky, Andrey

2015-01-01

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pKa values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD = pH + 0.4) values. The general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pKa values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pKa of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. These findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen. PMID:26392527

Excited-State Proton Transfer on the Surface of a Therapeutic Protein, Protamine.

PubMed

Awasthi, Ankur A; Singh, Prabhat K

2017-11-16

Proton transfer reactions on biosurfaces play an important role in a myriad of biological processes. Herein, the excited-state proton transfer reaction of 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) has been investigated in the presence of an important therapeutic protein, Protamine (PrS), using ground-state absorption, steady-state, and detailed time-resolved emission measurements. HPTS forms a 1:1 complex with Protamine with a high association constant of 2.6 × 10 4 M -1 . The binding of HPTS with Protamine leads to a significant modulation in the ground-state prototropic equilibrium causing a downward shift of 1.1 unit in the acidity constant (pK a ). In contrast to a large number of reports of slow proton transfer of HPTS on biosurfaces, interestingly, HPTS registers a faster proton transfer event in the presence of Protamine as compared to that of even the bulk aqueous buffer medium. Furthermore, the dimensionality of the proton diffusion process is also significantly reduced on the surface of Protamine that is in contrast to the behavior of HPTS in the bulk aqueous buffer medium, where the proton diffusion process is three-dimensional. The effect of ionic strength on the binding of HPTS toward PrS suggests a predominant role of electrostatic interaction between anionic HPTS and cationic Protamine, which is further supported by molecular docking simulations which predict that the most preferable binding site for HPTS on the surface of Protamine is surrounded by multiple cationic arginine residues.

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Qun; Parks, Jerry M.; Hanson, B. Leif

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pK a values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD = pH + 0.4) values. Themore » general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pK a values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pK a of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. Lastly, these findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen.« less

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography

DOE PAGES

Wan, Qun; Parks, Jerry M.; Hanson, B. Leif; ...

2015-09-21

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pK a values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD = pH + 0.4) values. Themore » general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pK a values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pK a of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. Lastly, these findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen.« less

Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy.

PubMed

Shiraishi, Yutaka; Xu, Cai; Yang, Jinzhong; Komaki, Ritsuko; Lin, Steven H

2017-10-01

To compare heart and cardiac substructure radiation exposure using intensity-modulated radiotherapy (IMRT) vs. proton beam therapy (PBT) for patients with mid- to distal esophageal cancer who received chemoradiation therapy. We identified 727 esophageal cancer patients who received IMRT (n=477) or PBT (n=250) from March 2004 to December 2015. All patients were treated to 50.4Gy with IMRT or to 50.4 cobalt Gray equivalents with PBT. IMRT and PBT dose-volume histograms (DVHs) of the whole heart, atria, ventricles, and four coronary arteries were compared. For PBT patients, passive scattering proton therapy (PSPT; n=237) and intensity-modulated proton therapy (IMPT; n=13) DVHs were compared. Compared with IMRT, PBT resulted in significantly lower mean heart dose (MHD) and heart V5, V10, V20, V30, and V40as well as lower radiation exposure to the four chambers and four coronary arteries. Compared with PSPT, IMPT resulted in significantly lower heart V20, V30, and V40 but not MHD or heart V5 or V10. IMPT also resulted in significantly lower radiation doses to the left atrium, right atrium, left main coronary artery, and left circumflex artery, but not the left ventricle, right ventricle, left anterior descending artery, or right coronary artery. Factors associated with lower MHD included PBT (P<0.001), smaller planning target volume (PTV; P<0.001), and gastroesophageal junction (GEJ) tumor (P<0.001). Among PBT patients, factors associated with lower MHD included IMPT (P=0.038), beam arrangement other than AP/PA (P<0.001), smaller PTV (P<0.001), and GEJ tumor (P<0.001). In patients with mid- to distal esophageal cancer, PBT results in significantly lower radiation exposure to the whole heart and cardiac substructures than IMRT. Long-term studies are necessary to determine how this cardiac sparing effect impacts the development of coronary artery disease and other cardiac complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study.

PubMed

Welsh, James; Gomez, Daniel; Palmer, Matthew B; Riley, Beverly A; Mayankkumar, Amin V; Komaki, Ritsuko; Dong, Lei; Zhu, X Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L; Ajani, Jaffer A; Cox, James D

2011-12-01

We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution. Copyright © 2011 Elsevier Inc. All rights reserved.

Precise Measurements of the Cosmic Ray Antiproton Spectrum with BESS Including the Effects of Solar Modulation

NASA Technical Reports Server (NTRS)

Mitchell, J. W.; Abe, K.; Anraku, K.; Asaoka, Y.; Fujikawa, M.; Fuke, H.; Haino, S.; Hams, T.; Ikeda, N.; Imori, M.

2002-01-01

The Balloon Borne Experiment with a Superconducting Spectrometer (BESS) has measured the energy spectrum of cosmic-ray antiprotons between 0.18 and 4.20 GeV in eight flights between 1993 and 2002. Above about 1 GeV, models in which antiprotons are secondary products of the interactions of primary cosmic rays with the interstellar gas agree with the BESS antiproton spectrum. Below 1 GeV, the data show a possible excess antiproton flux compared to secondary model predictions, suggesting the presence of an additional source of antiprotons. The antiproton/proton ratios measured between 1993 and 1999, during the Sun's positive-polarity phase, are consistent with simple models of solar modulation. However, results from the 2000 flight, following the solar magnetic field reversal, show a sudden increase in the antiproton/proton ratio and tend to favor a charge-sign-dependent drift model. To extend BESS measurements to lower energies, an evolutionary instrument, BESS-Polar, is under construction for polar flight in 2004.

Real-Time Remote Monitoring of Temperature and Humidity Within a Proton Exchange Membrane Fuel Cell Using Flexible Sensors

PubMed Central

Kuo, Long-Sheng; Huang, Hao-Hsiu; Yang, Cheng-Hao; Chen, Ping-Hei

2011-01-01

This study developed portable, non-invasive flexible humidity and temperature microsensors and an in situ wireless sensing system for a proton exchange membrane fuel cell (PEMFC). The system integrated three parts: a flexible capacitive humidity microsensor, a flexible resistive temperature microsensor, and a radio frequency (RF) module for signal transmission. The results show that the capacitive humidity microsensor has a high sensitivity of 0.83 pF%RH−1 and the resistive temperature microsensor also exhibits a high sensitivity of 2.94 × 10−3 °C−1. The established RF module transmits the signals from the two microsensors. The transmission distance can reach 4 m and the response time is less than 0.25 s. The performance measurements demonstrate that the maximum power density of the fuel cell with and without these microsensors are 14.76 mW·cm−2 and 15.90 mW·cm−2, with only 7.17% power loss. PMID:22164099

Initial observations of cavitation-induced erosion of liquid metal spallation target vessels at the Spallation Neutron Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClintock, David A; Riemer, Bernie; Ferguson, Phillip D

2012-01-01

During operation of the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory the mechanical properties of the AISI 316L target module are altered by high-energy neutron and proton radiation. The interior surfaces of the target vessel are also damaged by cavitation-induced erosion, which results from repetitive rapid heating of the liquid mercury by high-energy proton beam pulses. Until recently no observations of cavitation-induced erosion were possible for conditions prototypical to the SNS. Post irradiation examination (PIE) of the first and second operational SNS targets was performed to gain insight into the radiation-induced changes in mechanical properties of the 316Lmore » target material and the extent of cavitation-induced erosion to the target vessel inner surfaces. Observations of cavitation-induced erosion of the first and second operational SNS target modules are presented here, including images of the target vessel interiors and specimens removed from the target beam-entrance regions.« less

Phase modulation in dipolar-coupled A 2 spin systems: effect of maximum state mixing in 1H NMR in vivo

NASA Astrophysics Data System (ADS)

Schröder, Leif; Schmitz, Christian; Bachert, Peter

2004-12-01

Coupling constants of nuclear spin systems can be determined from phase modulation of multiplet resonances. Strongly coupled systems such as citrate in prostatic tissue exhibit a more complex modulation than AX connectivities, because of substantial mixing of quantum states. An extreme limit is the coupling of n isochronous spins (A n system). It is observable only for directly connected spins like the methylene protons of creatine and phosphocreatine which experience residual dipolar coupling in intact muscle tissue in vivo. We will demonstrate that phase modulation of this "pseudo-strong" system is quite simple compared to those of AB systems. Theory predicts that the spin-echo experiment yields conditions as in the case of weak interactions, in particular, the phase modulation depends linearly on the line splitting and the echo time.

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

NASA Astrophysics Data System (ADS)

Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

2008-03-01

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

Temporal variations of the anomalous oxygen component

NASA Technical Reports Server (NTRS)

Cummings, A. C.; Webber, W. R.

1983-01-01

Data from the cosmic ray experiment on Voyagers 1 and 2 was used to examine anomalous oxygen in the time period from launch in 1977 to the end of 1981. Several time periods were found where large periodic (typically 26 day) temporal variations of the oxygen intensity between approximately 5 - 15 MeV/nuc are present. Variations in intensity by up to a factor of 10 are observed during these periods. Several characteristics of these variations indicate that they are not higher energy extensions of the low energy particle (approximately 1 MeV/nuc) increases found in many corotating interaction regions (CIR's). Many of these periodic temporal variations are correlated with similar, but much smaller, recurrent variations in the 75 MeV proton rate. Voyager 1 and Voyager 2 counting rates were compared to estimate the local radial gradient for both the protons and the oxygen. The proton gradients during periods of both maximum and minumum fluxes are consistent with the overall positive radial gradients reported by others from Pioneer and near-Earth observations, supporting the view that these variations are due to local modulation of a source outside the radial range of project measurements. In contrast, the oxygen gradients during periods of maximum proton flux differ in sign from those during minimum proton fluxes, suggesting that the origin of the oxygen variations is different from that of the protons.

SU-F-T-148: Are the Approximations in Analytic Semi-Empirical Dose Calculation Algorithms for Intensity Modulated Proton Therapy for Complex Heterogeneities of Head and Neck Clinically Significant?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yepes, P; UT MD Anderson Cancer Center, Houston, TX; Titt, U

2016-06-15

Purpose: Evaluate the differences in dose distributions between the proton analytic semi-empirical dose calculation algorithm used in the clinic and Monte Carlo calculations for a sample of 50 head-and-neck (H&N) patients and estimate the potential clinical significance of the differences. Methods: A cohort of 50 H&N patients, treated at the University of Texas Cancer Center with Intensity Modulated Proton Therapy (IMPT), were selected for evaluation of clinical significance of approximations in computed dose distributions. H&N site was selected because of the highly inhomogeneous nature of the anatomy. The Fast Dose Calculator (FDC), a fast track-repeating accelerated Monte Carlo algorithm formore » proton therapy, was utilized for the calculation of dose distributions delivered during treatment plans. Because of its short processing time, FDC allows for the processing of large cohorts of patients. FDC has been validated versus GEANT4, a full Monte Carlo system and measurements in water and for inhomogeneous phantoms. A gamma-index analysis, DVHs, EUDs, and TCP and NTCPs computed using published models were utilized to evaluate the differences between the Treatment Plan System (TPS) and FDC. Results: The Monte Carlo results systematically predict lower dose delivered in the target. The observed differences can be as large as 8 Gy, and should have a clinical impact. Gamma analysis also showed significant differences between both approaches, especially for the target volumes. Conclusion: Monte Carlo calculations with fast algorithms is practical and should be considered for the clinic, at least as a treatment plan verification tool.« less

Comparison of two hardware-based hit filtering methods for trackers in high-pileup environments

NASA Astrophysics Data System (ADS)

Gradin, J.; Mårtensson, M.; Brenner, R.

2018-04-01

As experiments in high energy physics aim to measure increasingly rare processes, the experiments continually strive to increase the expected signal yields. In the case of the High Luminosity upgrade of the LHC, the luminosity is raised by increasing the number of simultaneous proton-proton interactions, so-called pile-up. This increases the expected yields of signal and background processes alike. The signal is embedded in a large background of processes that mimic that of signal events. It is therefore imperative for the experiments to develop new triggering methods to effectively distinguish the interesting events from the background. We present a comparison of two methods for filtering detector hits to be used for triggering on particle tracks: one based on a pattern matching technique using Associative Memory (AM) chips and the other based on the Hough transform. Their efficiency and hit rejection are evaluated for proton-proton collisions with varying amounts of pile-up using a simulation of a generic silicon tracking detector. It is found that, while both methods are feasible options for a track trigger with single muon efficiencies around 98–99%, the AM based pattern matching produces a lower number of hit combinations with respect to the Hough transform whilst keeping more of the true signal hits. We also present the effect on the two methods of increasing the amount of support material in the detector and of introducing inefficiencies by deactivating detector modules. The increased support material has negligable effects on the efficiency for both methods, while dropping 5% (10%) of the available modules decreases the efficiency to about 95% (87%) for both methods, irrespective of the amount of pile-up.

Balloon measurements of cosmic ray muon spectra in the atmosphere along with those of primary protons and helium nuclei over midlatitude

NASA Astrophysics Data System (ADS)

Bellotti, R.; Cafagna, F.; Circella, M.; de Marzo, C. N.; Golden, R. L.; Stochaj, S. J.; de Pascale, M. P.; Morselli, A.; Picozza, P.; Stephens, S. A.; Hof, M.; Menn, W.; Simon, M.; Mitchell, J. W.; Ormes, J. F.; Streitmatter, R. E.; Finetti, N.; Grimani, C.; Papini, P.; Piccardi, S.; Spillantini, P.; Basini, G.; Ricci, M.

1999-09-01

We report here the measurements of the energy spectra of atmospheric muons and of the parent cosmic ray primary proton and helium nuclei in a single experiment. These were carried out using the MASS superconducting spectrometer in a balloon flight experiment in 1991. The relevance of these results to the atmospheric neutrino anomaly is emphasized. In particular, this approach allows uncertainties caused by the level of solar modulation, the geomagnetic cut-off of the primaries and possible experimental systematics, to be decoupled in the comparison of calculated fluxes of muons to measured muon fluxes. The muon observations cover the momentum and depth ranges of 0.3-40 GeV/c and 5-886 g/cm2, respectively. A comparison of these results with those obtained in a previous experiment by the same collaboration using a similar apparatus allows us to search for differences due to the different experimental conditions at low energy and to check for the overall normalization between the two measurements. The proton and helium primary measurements cover the rigidity range from 3 to 100 GV, in which both the solar modulation and the geomagnetic cut-off affect the energy spectra at low energies. From the observed low-energy helium spectrum, the geomagnetic transmission function at mid-latitude has been determined.

Solution of Heliospheric Propagation: Unveiling the Local Interstellar Spectra of Cosmic-ray Species

NASA Astrophysics Data System (ADS)

Boschini, M. J.; Della Torre, S.; Gervasi, M.; Grandi, D.; Jóhannesson, G.; Kachelriess, M.; La Vacca, G.; Masi, N.; Moskalenko, I. V.; Orlando, E.; Ostapchenko, S. S.; Pensotti, S.; Porter, T. A.; Quadrani, L.; Rancoita, P. G.; Rozza, D.; Tacconi, M.

2017-05-01

Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.

VizieR Online Data Catalog: Local interstellar spectra of cosmic-ray species (Boschini+, 2017)

NASA Astrophysics Data System (ADS)

Boschini, M. J.; Torre, S. D.; Gervasi, M.; Grandi, D.; Johannesson, G.; Kachelriess, M.; La Vacca, G.; Masi, N.; Moskalenko, I. V.; Orlando, E.; Ostapchenko, S. S.; Pensotti, S.; Porter, T. A.; Quadrani, L.; Rancoita, P. G.; Rozza, D.; Tacconi, M.

2017-11-01

Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range. (3 data files).

Solution of Heliospheric Propagation: Unveiling the Local Interstellar Spectra of Cosmic-ray Species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boschini, M. J.; Torre, S. Della; Gervasi, M.

2017-05-10

Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with themore » data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.« less

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

PubMed

Eekers, Daniëlle B P; Roelofs, Erik; Jelen, Urszula; Kirk, Maura; Granzier, Marlies; Ammazzalorso, Filippo; Ahn, Peter H; Janssens, Geert O R J; Hoebers, Frank J P; Friedmann, Tobias; Solberg, Timothy; Walsh, Sean; Troost, Esther G C; Kaanders, Johannes H A M; Lambin, Philippe

2016-12-01

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

WE-EF-303-10: Single- Detector Proton Radiography as a Portal Imaging Equivalent for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doolan, P; Bentefour, E; Testa, M

2015-06-15

Purpose: In proton therapy, patient alignment is of critical importance due to the sensitivity of the proton range to tissue heterogeneities. Traditionally proton radiography is used for verification of the water-equivalent path length (WEPL), which dictates the depth protons reach. In this work we propose its use for alignment. Additionally, many new proton centers have cone-beam computed tomography in place of beamline X-ray imaging and so proton radiography offers a unique patient alignment verification similar to portal imaging in photon therapy. Method: Proton radiographs of a CIRS head phantom were acquired using the Beam Imaging System (BIS) (IBA, Louvain-la-Neuve) inmore » a horizontal beamline. A scattered beam was produced using a small, dedicated, range modulator (RM) wheel fabricated out of aluminum. The RM wheel was rotated slowly (20 sec/rev) using a stepper motor to compensate for the frame rate of the BIS (120 ms). Dose rate functions (DRFs) over two RM wheel rotations were acquired. Calibration was made with known thicknesses of homogeneous solid water. For each pixel the time width, skewness and kurtosis of the DRFs were computed. The time width was used to compute the object WEPL. In the heterogeneous phantom, the excess skewness and excess kurtosis (i.e. difference from homogeneous cases) were computed and assessed for suitability for patient set up. Results: The technique allowed for the simultaneous production of images that can be used for WEPL verification, showing few internal details, and excess skewness and kurtosis images that can be used for soft tissue alignment. These latter images highlight areas where range mixing has occurred, correlating with phantom heterogeneities. Conclusion: The excess skewness and kurtosis images contain details that are not visible in the WET images. These images, unique to the time-resolved proton radiographic method, could be used for patient set up according to soft tissues.« less

An Empirical Modification of the Force Field Approach to Describe the Modulation of Galactic Cosmic Rays Close to Earth in a Broad Range of Rigidities

NASA Astrophysics Data System (ADS)

Gieseler, J.; Heber, B.; Herbst, K.

2017-11-01

On their way through the heliosphere, galactic cosmic rays (GCRs) are modulated by various effects before they can be detected at Earth. This process can be described by the Parker equation, which calculates the phase space distribution of GCRs depending on the main modulation processes: convection, drifts, diffusion, and adiabatic energy changes. A first-order approximation of this equation is the force field approach, reducing it to a one-parameter dependency, the solar modulation potential ϕ. Utilizing this approach, it is possible to reconstruct ϕ from ground-based and spacecraft measurements. However, it has been shown previously that ϕ depends not only on the local interstellar spectrum (LIS) but also on the energy range of interest. We have investigated this energy dependence further, using published proton intensity spectra obtained by PAMELA and heavier nuclei measurements from IMP-8 and ACE/CRIS. Our results show severe limitations at lower energies including a strong dependence on the solar magnetic epoch. Based on these findings, we will outline a new tool to describe GCR proton spectra in the energy range from a few hundred MeV to tens of GeV over the last solar cycles. In order to show the importance of our modification, we calculate the global production rates of the cosmogenic radionuclide 10Be which is a proxy for the solar activity ranging back thousands of years.

Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

PubMed Central

Brady, Roscoe O; McCarthy, Julie M; Prescot, Andrew P; Jensen, J Eric; Cooper, Alissa J; Cohen, Bruce M; Renshaw, Perry F; Ongür, Dost

2017-01-01

Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition. PMID:23634979

Mars surface radiation exposure for solar maximum conditions and 1989 solar proton events

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Nealy, John E.

1992-01-01

The Langley heavy-ion/nucleon transport code, HZETRN, and the high-energy nucleon transport code, BRYNTRN, are used to predict the propagation of galactic cosmic rays (GCR's) and solar flare protons through the carbon dioxide atmosphere of Mars. Particle fluences and the resulting doses are estimated on the surface of Mars for GCR's during solar maximum conditions and the Aug., Sep., and Oct. 1989 solar proton events. These results extend previously calculated surface estimates for GCR's at solar minimum conditions and the Feb. 1956, Nov. 1960, and Aug. 1972 solar proton events. Surface doses are estimated with both a low-density and a high-density carbon dioxide model of the atmosphere for altitudes of 0, 4, 8, and 12 km above the surface. A solar modulation function is incorporated to estimate the GCR dose variation between solar minimum and maximum conditions over the 11-year solar cycle. By using current Mars mission scenarios, doses to the skin, eye, and blood-forming organs are predicted for short- and long-duration stay times on the Martian surface throughout the solar cycle.

Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy.

PubMed

Spugnini, Enrico P; Citro, Gennaro; Fais, Stefano

2010-05-08

The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.

Two-dimensional dosimetry of radiotherapeutical proton beams using thermoluminescence foils.

PubMed

Czopyk, L; Klosowski, M; Olko, P; Swakon, J; Waligorski, M P R; Kajdrowicz, T; Cuttone, G; Cirrone, G A P; Di Rosa, F

2007-01-01

In modern radiation therapy such as intensity modulated radiation therapy or proton therapy, one is able to cover the target volume with improved dose conformation and to spare surrounding tissue with help of modern measurement techniques. Novel thermoluminescence dosimetry (TLD) foils, developed from the hot-pressed mixture of LiF:Mg,Cu,P (MCP TL) powder and ethylene-tetrafluoroethylene (ETFE) copolymer, have been applied for 2-D dosimetry of radiotherapeutical proton beams at INFN Catania and IFJ Krakow. A TLD reader with 70 mm heating plate and CCD camera was used to read the 2-D emission pattern of irradiated foils. The absorbed dose profiles were evaluated, taking into account correction factors specific for TLD such as dose and energy response. TLD foils were applied for measuring of dose distributions within an eye phantom and compared with predictions obtained from the MCNPX code and Eclipse Ocular Proton Planning (Varian Medical Systems) clinical radiotherapy planning system. We demonstrate the possibility of measuring 2-D dose distributions with point resolution of about 0.5 x 0.5 mm(2).

Water equivalent path length measurement in proton radiotherapy using time resolved diode dosimetry

PubMed Central

Gottschalk, B.; Tang, S.; Bentefour, E. H.; Cascio, E. W.; Prieels, D.; Lu, H.-M.

2011-01-01

Purpose: To verify water equivalent path length (WEPL) before treatment in proton radiotherapy using time resolved in vivo diode dosimetry. Methods: Using a passively scattered range modulated proton beam, the output of a diode driving a fast current-to-voltage amplifier is recorded at a number of depths in a water tank. At each depth, a burst of overlapping single proton pulses is observed. The rms duration of the burst is computed and the resulting data set is fitted with a cubic polynomial. Results: When the diode is subsequently set to an arbitrary depth and the polynomial is used as a calibration curve, the “unknown” depth is determined within 0.3 mm rms. Conclusions: A diode or a diode array, placed (for instance) in the rectum in conjunction with a rectal balloon, can potentially determine the WEPL at that point, just prior to treatment, with submillimeter accuracy, allowing the beam energy to be adjusted. The associated unwanted dose is about 0.2% of a typical single fraction treatment dose. PMID:21626963

Deep Proton Writing for the rapid prototyping of polymer micro-components for optical interconnects and optofluidics

NASA Astrophysics Data System (ADS)

Van Erps, Jürgen; Vervaeke, Michael; Ottevaere, Heidi; Hermanne, Alex; Thienpont, Hugo

2013-07-01

The use of photonics in data communication and numerous other industrial applications brought plenty of prospects for innovation and opened up different unexplored market opportunities. This is a major driving force for the fabrication of micro-optical and micro-mechanical structures and their accurate alignment and integration into opto-mechanical modules and systems. To this end, we present Deep Proton Writing (DPW) as a powerful rapid prototyping technology for such micro-components. The DPW process consists of bombarding polymer samples (PMMA or SU-8) with swift protons, which results after chemical processing steps in high-quality micro-optical components. One of the strengths of the DPW micro-fabrication technology is the ability to fabricate monolithic building blocks that include micro-optical and mechanical functionalities which can be precisely integrated into more complex photonic systems. In this paper we comment on how we shifted from using 8.3 to 16.5 MeV protons for DPW and give some examples of micro-optical and micro-mechanical components recently fabricated through DPW, targeting applications in optical interconnections and in optofluidics.

High energy proton induced radiation damage of rare earth permanent magnet quadrupoles

NASA Astrophysics Data System (ADS)

Schanz, M.; Endres, M.; Löwe, K.; Lienig, T.; Deppert, O.; Lang, P. M.; Varentsov, D.; Hoffmann, D. H. H.; Gutfleisch, O.

2017-12-01

Permanent magnet quadrupoles (PMQs) are an alternative to common electromagnetic quadrupoles especially for fixed rigidity beam transport scenarios at particle accelerators. Using those magnets for experimental setups can result in certain scenarios, in which a PMQ itself may be exposed to a large amount of primary and secondary particles with a broad energy spectrum, interacting with the magnetic material and affecting its magnetic properties. One specific scenario is proton microscopy, where a proton beam traverses an object and a collimator in which a part of the beam is scattered and deflected into PMQs used as part of a diagnostic system. During the commissioning of the PRIOR (Proton Microscope for Facility for Antiproton and Ion Research) high energy proton microscope facility prototype at Gesellschaft für Schwerionenforschung in 2014, a significant reduction of the image quality was observed which was partially attributed to the demagnetization of the used PMQ lenses and the corresponding decrease of the field quality. In order to study this phenomenon, Monte Carlo simulations were carried out and spare units manufactured from the same magnetic material—single wedges and a fully assembled PMQ module—were deliberately irradiated by a 3.6 GeV intense proton beam. The performed investigations have shown that in proton radiography applications the above described scattering may result in a high irradiation dose in the PMQ magnets. This did not only decrease the overall magnetic strength of the PMQs but also caused a significant degradation of the field quality of an assembled PMQ module by increasing the parasitic multipole field harmonics which effectively makes PMQs impractical for proton radiography applications or similar scenarios.

Electrocatalysis-induced elasticity modulation in a superionic proton conductor probed by band-excitation atomic force microscopy.

PubMed

Papandrew, A B; Li, Q; Okatan, M B; Jesse, S; Hartnett, C; Kalinin, S V; Vasudevan, R K

2015-12-21

Variable temperature band-excitation atomic force microscopy in conjunction with I-V spectroscopy was used to investigate the crystalline superionic proton conductor CsHSO4 during proton exchange induced by a Pt-coated conductive scanning probe. At a sample temperature of 150 °C and under an applied bias <1 V, reduction currents of up to 1 nA were observed. Simultaneously, we show that the electrochemical reactions are accompanied by a reversible decrease in the elastic modulus of CsHSO4, as seen by a contact resonance shift, and find evidence for superplasticity during scanning. These effects were not observed in the room-temperature phase of CsHSO4 or in the case of catalytically inactive conductive probes, proving the utility of this technique for monitoring electrochemical processes on the nanoscale, as well as the use of local contact stiffness as a sensitive indicator of electrochemical reactions.

Anesthetic Diffusion Through Lipid Membranes Depends on the Protonation Rate

PubMed Central

Pérez-Isidoro, Rosendo; Sierra-Valdez, F. J.; Ruiz-Suárez, J. C.

2014-01-01

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon. PMID:25520016

Evidence that protons act as neurotransmitters at vestibular hair cell-calyx afferent synapses.

PubMed

Highstein, Stephen M; Holstein, Gay R; Mann, Mary Anne; Rabbitt, Richard D

2014-04-08

Present data support the conclusion that protons serve as an important neurotransmitter to convey excitatory stimuli from inner ear type I vestibular hair cells to postsynaptic calyx nerve terminals. Time-resolved pH imaging revealed stimulus-evoked extrusion of protons from hair cells and a subsequent buildup of [H(+)] within the confined chalice-shaped synaptic cleft (ΔpH ∼ -0.2). Whole-cell voltage-clamp recordings revealed a concomitant nonquantal excitatory postsynaptic current in the calyx terminal that was causally modulated by cleft acidification. The time course of [H(+)] buildup limits the speed of this intercellular signaling mechanism, but for tonic signals such as gravity, protonergic transmission offers a significant metabolic advantage over quantal excitatory postsynaptic currents--an advantage that may have driven the proliferation of postsynaptic calyx terminals in the inner ear vestibular organs of contemporary amniotes.

The Node 1 (or Unity) Module for the International Space Station

NASA Technical Reports Server (NTRS)

1997-01-01

This photograph, taken by the Boeing Company, shows Node 1 (also called Unity), the first U.S. Module for the International Space Station (ISS), with its hatch door installed. The Node 1, or Unity, serves as a cornecting passageway to Space Station modules and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian-built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

Rational design of a colorimetric pH sensor from a soluble retinoic acid chaperone.

PubMed

Berbasova, Tetyana; Nosrati, Meisam; Vasileiou, Chrysoula; Wang, Wenjing; Lee, Kin Sing Stephen; Yapici, Ipek; Geiger, James H; Borhan, Babak

2013-10-30

Reengineering of cellular retinoic acid binding protein II (CRABPII) to be capable of binding retinal as a protonated Schiff base is described. Through rational alterations of the binding pocket, electrostatic perturbations of the embedded retinylidene chromophore that favor delocalization of the iminium charge lead to exquisite control in the regulation of chromophoric absorption properties, spanning the visible spectrum (474-640 nm). The pKa of the retinylidene protonated Schiff base was modulated from 2.4 to 8.1, giving rise to a set of proteins of varying colors and pH sensitivities. These proteins were used to demonstrate a concentration-independent, ratiometric pH sensor.

A 62-MeV Proton Beam for the Treatment of Ocular Melanoma at Laboratori Nazionali del Sud-INFN

NASA Astrophysics Data System (ADS)

Cirrone, G. A. P.; Cuttone, G.; Lojacono, P. A.; Lo Nigro, S.; Mongelli, V.; Patti, I. V.; Privitera, G.; Raffaele, L.; Rifuggiato, D.; Sabini, M. G.; Salamone, V.; Spatola, C.; Valastro, L. M.

2004-06-01

At the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) in Catania, Italy, the first Italian protontherapy facility, named Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA) has been built in collaboration with the University of Catania. It is based on the use of the 62-MeV proton beam delivered by the K=800 Superconducting Cyclotron installed and working at INFN-LNS since 1995. The facility is mainly devoted to the treatment of ocular diseases like uveal melanoma. A beam treatment line in air has been assembled together with a dedicated positioning patient system. The facility has been in operation since the beginning of 2002 and 66 patients have been successfully treated up to now. The main features of CATANA together with the clinical and dosimetric features will be extensively described; particularly, the proton beam line, that has been entirely built at LNS, with all its elements, the experimental transversal and depth dose distributions of the 62-MeV proton beam obtained for a final collimator of 25-mm diameter and the experimental depth dose distributions of a modulated proton beam obtained for the same final collimator. Finally, the clinical results over 1 yr of treatments, describing the features of the treated diseases will be reported.

Design, construction and tests of a 3 GHz proton linac booster (LIBO) for cancer therapy

NASA Astrophysics Data System (ADS)

Berra, Paolo

2007-12-01

In the last ten years the use of proton beams in radiation therapy has become a clinical tool for treatment of deep-seated tumours. LIBO is a RF compact and low cost proton linear accelerator (SCL type) for hadrontherapy. It is conceived by TERA Foundation as a 3 GHz Linac Booster, to be mounted downstream of an existing cyclotron in order to boost the energy of the proton beam up to 200 MeV, needed for deep treatment (~25 cm) in the human body. With this solution it is possible to transform a low energy commercial cyclotron, normally used for eye melanoma therapy, isotope production and nuclear physics research, into an accelerator for deep-seated tumours. A prototype module of LIBO has been built and successfully tested with full RF power at CERN and with proton beam at INFN Laboratori Nazionali del Sud (LNS) in Catania, within an international collaboration between TERA Foundation, CERN, the Universities and INFN groups of Milan and Naples. The mid-term aim of the project is the technology transfer of the accumulated know-how to a consortium of companies and to bring this novel medical tool to hospitals. The design, construction and tests of the LIBO prototype are described in detail.

Splash albedo protons between 4 and 315 MeV at high and low geomagnetic latitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wenzel, K.; Stone, E.C.; Vogt, R.E.

1975-09-01

The differential energy spectrum of splash albedo protons has been measured at high geomagnetic latitude near Fort Churchill, Manitoba, at three periods of the solar cycle in 1966, and 1969 and at low latitude near Palestine, Texas, in 1967 by using a balloon-borne solid state detector telescope. We observed splash albedo proton fluxes between 4 and 315 MeV of 81plus-or-minus11, 70plus-or-minus11, and 48plus-or-minus8 protons/(m$sup 2$s sr) at high latitude in 1966, 1967, and 1969 and of 37plus-or-minus9 protons/(m$sup 2$s sr) at low latitude in 1967. The decreases from 1966 to 1969 are due to solar modulation of the cosmic raymore » parent nuclei. The albedo spectrum shows a similar shape for both latitudes. The difference in intensity can be explained by different local geomagnetic cutoffs; i.e., a significant contribution to the splash albedo flux arises from primary particles with rigidity below 4.5 GV. The splash albedo flux near Fort Churchill is consistent with corresponding fluxes previously reported near 53degree--55degreeN. The flux below 100 MeV near Palestine is significantly lower than that reported by Verma (1967).« less

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

STS-88 Onboard Photograph - The Unity Module and the Zarya

NASA Technical Reports Server (NTRS)

1998-01-01

This photograph taken during the STS-88 mission, shows the cornected Zarya (top with solar wings) and the Unity Module after having been released from the Orbiter Endeavour's cargo bay. The Unity (also called Node 1), the first U.S. Module for the International Space Station (ISS), is a six-sided connector to which all future U.S. Station modules will attach and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

STS-88 Onboard Photograph - Unity and Zarya Modules

NASA Technical Reports Server (NTRS)

1998-01-01

This photograph, taken during the STS-88 mission, shows the cornected Unity Module or Node 1 and Zarya or the Functional Cargo Block (FGB) after having been released from the Orbiter Endeavour's cargo bay. The Unity (also called Node 1), the first U.S. Module for the International Space Station (ISS), is a six-sided connector to which all future U.S. Station modules will attach. It was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity Module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

The potential of intensity-modulated proton radiotherapy to reduce swallowing dysfunction in the treatment of head and neck cancer: A planning comparative study.

PubMed

van der Laan, Hans Paul; van de Water, Tara A; van Herpt, Heleen E; Christianen, Miranda E M C; Bijl, Hendrik P; Korevaar, Erik W; Rasch, Coen R; van 't Veld, Aart A; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A

2013-04-01

Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction. Still the risk is high. The aim of this study was to determine the potential of swallowing-sparing (SW) intensity-modulated proton therapy (IMPT) in head and neck cancer (HNC) for reducing the risk of swallowing dysfunction relative to currently used photon therapy. Twenty-five patients with oropharyngeal (n = 21) and hypopharyngeal (n = 4) cancer received primary radiotherapy, including bilateral neck irradiation, using standard (ST) intensity-modulated photon therapy (IMRT). Prophylactic (54 Gy) and therapeutic (70 Gy) target volumes were defined. The dose to the parotid and submandibular glands was reduced as much as possible. Four additional radiotherapy plans were created for each patient: SW-IMRT, ST-IMPT, 3-beam SW-IMPT (3B-SW-IMPT) and 7-beam SW-IMPT (7B-SW-IMPT). All plans were optimized similarly, with additional attempts to spare the swallowing organs at risk (SWOARs) in the SW plans. Probabilities of swallowing dysfunction were calculated with recently developed predictive models. All plans complied with standard HNC radiotherapy objectives. The mean parotid gland doses were similar for the ST and SW photon plans, but clearly lower in all IMPT plans (ipsilateral parotid gland ST-IMRT: 46 Gy, 7B-SW-IMPT: 29 Gy). The mean dose in the SWOARs was lowest with SW-IMPT, in particular with 7B-SW-IMPT (supraglottic larynx ST-IMRT: 60 Gy, 7B-SW-IMPT: 40 Gy). The observed dose reductions to the SWOARs translated into substantial overall reductions in normal tissue complication risks for different swallowing dysfunction endpoints. Compared with ST-IMRT, the risk of physician-rated grade 2-4 swallowing dysfunction was reduced on average by 8.8% (95% CI 6.5-11.1%) with SW-IMRT, and by 17.2% (95% CI: 12.7-21.7%) with 7B-SW-IMPT. SWOAR-sparing with proton therapy has the potential to substantially reduce the risk of swallowing dysfunction compared to similar treatment with photons.

Modulation of lens cell adhesion molecules by particle beams

NASA Technical Reports Server (NTRS)

McNamara, M. P.; Bjornstad, K. A.; Chang, P. Y.; Chou, W.; Lockett, S. J.; Blakely, E. A.

2001-01-01

Cell adhesion molecules (CAMs) are proteins which anchor cells to each other and to the extracellular matrix (ECM), but whose functions also include signal transduction, differentiation, and apoptosis. We are testing a hypothesis that particle radiations modulate CAM expression and this contributes to radiation-induced lens opacification. We observed dose-dependent changes in the expression of beta 1-integrin and ICAM-1 in exponentially-growing and confluent cells of a differentiating human lens epithelial cell model after exposure to particle beams. Human lens epithelial (HLE) cells, less than 10 passages after their initial culture from fetal tissue, were grown on bovine corneal endothelial cell-derived ECM in medium containing 15% fetal bovine serum and supplemented with 5 ng/ml basic fibroblast growth factor (FGF-2). Multiple cell populations at three different stages of differentiation were prepared for experiment: cells in exponential growth, and cells at 5 and 10 days post-confluence. The differentiation status of cells was characterized morphologically by digital image analysis, and biochemically by Western blotting using lens epithelial and fiber cell-specific markers. Cultures were irradiated with single doses (4, 8 or 12 Gy) of 55 MeV protons and, along with unirradiated control samples, were fixed using -20 degrees C methanol at 6 hours after exposure. Replicate experiments and similar experiments with helium ions are in progress. The intracellular localization of beta 1-integrin and ICAM-1 was detected by immunofluorescence using monoclonal antibodies specific for each CAM. Cells known to express each CAM were also processed as positive controls. Both exponentially-growing and confluent, differentiating cells demonstrated a dramatic proton-dose-dependent modulation (upregulation for exponential cells, downregulation for confluent cells) and a change in the intracellular distribution of the beta 1-integrin, compared to unirradiated controls. In contrast, there was a dose-dependent increase in ICAM-1 immunofluorescence in confluent, but not exponentially-growing cells. These results suggest that proton irradiation downregulates beta 1-integrin and upregulates ICAM-1, potentially contributing to cell death or to aberrant differentiation via modulation of anchorage and/or signal transduction functions. Quantification of the expression levels of the CAMs by Western analysis is in progress.

SU-E-T-326: Dosimetric Impact of Beam Energies and Jaw Tracking On Intracranial Tumors Using RapidArc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ali, I

2015-06-15

Purpose: To determine the dosimetric impact of jaw tracking and beam energies on dose conformity and normal-brain-tissue doses for intracranial tumors using VMAT (RapidArc). Methods: Seven patients with 1–2 and three patients with 4–6 intracranial tumors were planned using RapidArc for Varian TrueBeam STx machine with beam energies 6MV-FFF (Flattening-Filter-Free), 8MV, 10MV, and 10MV-FFF. The prescription dose ranged from 14–23Gy. Between 2 and 8 arcs were used with the following geometries: 2 full coplanar arcs and the non-coplanar half arcs. Plans were optimized (jaw tracking ON) with a high priority to Normal-Tissue-Objective and normal-brain-tissue. Plans were calculated on 1mm gridmore » size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plans for the 6MV-FFF were also optimized without jaw tracking (No-JT) for comparison. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4Gy, V8Gy and V12Gy, and integral dose. Results: The average PCI ± standard deviation was 0.76±0.21 and 0.76±0.22 for 6MV-FFF and 10 MV-FFF, respectively. The average ratio in normal brain tissue volume (reported as follows V4,V8,V12) were (1.12±0.07,1.12±0.07,1.14±0.04), (1.12±0.08,1.12±0.09,1.13±0.06), (1.19±0.10,1.18±0.10,1.20±0.04), and (1.04±0.03,1.03±0.03,1.03±0.04) for 8MV/6MV-FFF, 10MV-FFF/6MV-FFF, 10MV/6MV-FFF, 6MV-FFF No-JT/6MV-FFF, respectively. Statistically significant differences in normal-brain-tissue for V4, V8, and V12 were observed in all cases for the different energies (p-values <0.05). V4 data shows significant differences in JT vs. No-JT (p=0.04), however no difference was found for V8 and V12. Brain tissue sparing from best to worst occurred in this order 6MV-FFF, 6MV-FFF no-JT, 10MV-FFF, 8MV, and 10MV. The average ratio of integral brain dose was 1.05±0.04 (p=0.21), 1.04±0.05 (p=0.33), 1.09±0.06 (p=0.04), and 1.02±0.06 (p=0.61) for 8MV/6MV-FFF, 10MV-FFF/6MV-FFF, 10MV/6MV-FFF, and 6MV-FFF No-JT/6MV-FFF, respectively. Conclusion: Normal brain tissue and integral dose improved using the lower energy and FFF beams, though plan conformity showed energy independence.« less

Evaluating Intensity Modulated Proton Therapy relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in CSI in Growing Pediatric Patients

PubMed Central

Giantsoudi, Drosoula; Seco, Joao; Eaton, Bree R.; Simeone, F. Joseph; Kooy, Hanne; Yock, Torunn I.; Tarbell, Nancy J; DeLaney, Thomas F.; Adams, Judith; Paganetti, Harald; MacDonald, Shannon M.

2017-01-01

Purpose At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aim to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. Methods Five plans were generated for medulloblastoma patients, previously treated with CSI PS proton radiation therapy (PRT): (a) single posterior-anterior (PA) PS field covering the WVB (PS-PA-WVB), (b) single PA PS field including only the thecal sac in the target volume (PS-PA-VBS), (c) single PA IMPT field covering the WVB (IMPT-PA-WVB), (d) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS) and (e) two posterior-oblique (−35°, 35°) IMPT fields, target volume including thecal sac only (IMPT2F-VBS). For all cases, 23.4Gy(RBE) was prescribed to 95% of the spinal canal. Dose, LET and variable-RBE-weighted dose distributions were calculated for all plans using the TOPAS Monte Carlo system. Results IMPT VBS techniques spared efficiently the anterior vertebral bodies (AVB), even when accounting for potential higher variable RBE predicted by linear energy transfer (LET) distributions. Assuming RBE=1.1, V10Gy(RBE) decreased from 100% for the WVB techniques to 59.5–76.8% for the cervical, 29.9–34.6% for the thoracic and 20.6–25.1% for the lumbar, and V20Gy(RBE) decreased from 99.0% to 17.8–20.0% for the cervical, 7.2–7.6% for the thoracic and 4.0–4.6% for the lumbar AVB when IMPT VBS techniques were applied. Corresponding values for the PS VBS technique were higher. Conclusions Advanced proton techniques may sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with CNS tumors requiring CSI. This holds even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children. PMID:28587051

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients.

PubMed

Giantsoudi, Drosoula; Seco, Joao; Eaton, Bree R; Simeone, F Joseph; Kooy, Hanne; Yock, Torunn I; Tarbell, Nancy J; DeLaney, Thomas F; Adams, Judith; Paganetti, Harald; MacDonald, Shannon M

2017-05-01

At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boehling, Nicholas S.; Grosshans, David R., E-mail: dgrossha@mdanderson.org; Bluett, Jaques B.

Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV)more » coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk-Operator }, 34.4%{sup Asterisk-Operator }) were recorded with the use of proton therapy. ({sup Asterisk-Operator }Differences were significant based on Friedman's test with Bonferroni-Dunn correction, {alpha} = 0.05) Conclusions: The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.« less

Effects of unsaturated fatty acids on the kinetics of voltage‐gated proton channels heterologously expressed in cultured cells

PubMed Central

Kawanabe, Akira

2016-01-01

Key points Arachidonic acid (AA) greatly enhances the activity of the voltage‐gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear.In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells.The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage‐dependence of activation.Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms.Application of phospholipase A2, which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Abstract Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage‐gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside‐out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current–voltage relationship. In monomeric channels lacking the coiled‐coil region of the channel protein, the shift in the current–voltage relationship was diminished but activation and deactivation remained accelerated. Studies with several AA derivatives showed that double bonds and hydrophilic head groups are essential for the effect of AA, although charge was not important. The application of phospholipase A2 (PLA2), which generates AA from cell membrane phospholipids, stimulated mHv1 activity to a similar extent as direct application of ∼20 μm AA, suggesting that endogenous AA may regulate Hv channel activity. PMID:26563684

Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Romaine C., E-mail: rnichols@floridaproton.org; Huh, Soon N.; Prado, Karl L.

2012-05-01

Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of themore » target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.« less

Protons offer reduced normal-tissue exposure for patients receiving postoperative radiotherapy for resected pancreatic head cancer.

PubMed

Nichols, Romaine C; Huh, Soon N; Prado, Karl L; Yi, Byong Y; Sharma, Navesh K; Ho, Meng W; Hoppe, Bradford S; Mendenhall, Nancy P; Li, Zuofeng; Regine, William F

2012-05-01

To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting. Copyright © 2012 Elsevier Inc. All rights reserved.

Ion dynamics during the parametric instabilities of a left-hand polarized Alfvén wave in a proton-electron-alpha plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Xinliang; Lu, Quanming; Hao, Yufei

2014-01-01

The parametric instabilities of an Alfvén wave in a proton-electron plasma system are found to have great influence on proton dynamics, where part of the protons can be accelerated through the Landau resonance with the excited ion acoustic waves, and a beam component along the background magnetic field is formed. In this paper, with a one-dimensional hybrid simulation model, we investigate the evolution of the parametric instabilities of a monochromatic left-hand polarized Alfvén wave in a proton-electron-alpha plasma with a low beta. When the drift velocity between the protons and alpha particles is sufficiently large, the wave numbers of themore » backward daughter Alfvén waves can be cascaded toward higher values due to the modulational instability during the nonlinear evolution of the parametric instabilities, and the alpha particles are resonantly heated in both the parallel and perpendicular direction by the backward waves. On the other hand, when the drift velocity of alpha particles is small, the alpha particles are heated in the linear growth stage of the parametric instabilities due to the Landau resonance with the excited ion acoustic waves. Therefore, the heating occurs only in the parallel direction, and there is no obvious heating in the perpendicular direction. The relevance of our results to the preferential heating of heavy ions observed in the solar wind within 0.3 AU is also discussed in this paper.« less

SU-F-T-212: A Comparison of Treatment Strategies for Intracranial Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamberton, T; Slater, J; Wroe, A

2016-06-15

Purpose: Stereotactic radiosurgery is an effective and noninvasive treatment for intracranial lesions that uses highly focused radiation beams in a single treatment fraction. The purpose of this study is to investigate the dosimetric differences between the treatment brain metastasis with a proton beam vs. intensity modulated radiation therapy (IMRT). Methods: Ten separate brain metastasis targets where chosen and treatment plans were created for each, using three different strategies: custom proton beam shaping devices, standardized proton beam shaping devices, and IMRT. Each plan was required to satisfy set parameters for providing adequate coverage and minimizing risk to adjacent tissues. The effectivenessmore » of each plan was calculated by comparing the homogeneity index, conformity index, and V12 for each target using a paired one tailed T-test (α=0.05). Specific comparison of the conformity indices was also made using a subcategory containing targets with volume>1cc. Results: There was no significant difference between the homogeneity indices of the three plans (p>0.05), showing that each plan has the capability of adequately covering the targets. There was a statistically significant difference (p<0.01) between the conformity indices of the custom and the standard proton plan, as with the custom proton and IMRT (p<0.01), with custom proton showing stronger conformity to the target in both cases. There was also a statistical difference between the V12 of all three plans (Custom v. Standardized: p=0.02, Custom v. IMRT: p<0.01, Standardized v. IMRT: p<0.01) with custom proton supplying the lowest dose to surrounding tissues. For large targets (volume>1cc) there was no statistical difference between the proton plans and the IMRT treatment for the conformity index. Conclusion: A custom proton plan is the recommended treatment explored in this study as it is the most reliable way of effectively treating the target while sparing the maximum amount of normal tissue.« less

Investigation of time-resolved proton radiography using x-ray flat-panel imaging system

NASA Astrophysics Data System (ADS)

Jee, K.-W.; Zhang, R.; Bentefour, E. H.; Doolan, P. J.; Cascio, E.; Sharp, G.; Flanz, J.; Lu, H.-M.

2017-03-01

Proton beam therapy benefits from the Bragg peak and delivers highly conformal dose distributions. However, the location of the end-of-range is subject to uncertainties related to the accuracy of the relative proton stopping power estimates and thereby the water-equivalent path length (WEPL) along the beam. To remedy the range uncertainty, an in vivo measurement of the WEPL through the patient, i.e. a proton-range radiograph, is highly desirable. Towards that goal, we have explored a novel method of proton radiography based on the time-resolved dose measured by a flat panel imager (FPI). A 226 MeV pencil beam and a custom-designed range modulator wheel (MW) were used to create a time-varying broad beam. The proton imaging technique used exploits this time dependency by looking at the dose rate at the imager as a function of time. This dose rate function (DRF) has a unique time-varying dose pattern at each depth of penetration. A relatively slow rotation of the MW (0.2 revolutions per second) and a fast image acquisition (30 frames per second, ~33 ms sampling) provided a sufficient temporal resolution for each DRF. Along with the high output of the CsI:Tl scintillator, imaging with pixel binning (2  ×  2) generated high signal-to-noise data at a very low radiation dose (~0.1 cGy). Proton radiographs of a head phantom and a Gammex CT calibration phantom were taken with various configurations. The results of the phantom measurements show that the FPI can generate low noise and high spatial resolution proton radiographs. The WEPL values of the CT tissue surrogate inserts show that the measured relative stopping powers are accurate to ~2%. The panel did not show any noticeable radiation damage after the accumulative dose of approximately 3831 cGy. In summary, we have successfully demonstrated a highly practical method of generating proton radiography using an x-ray flat panel imager.

Investigation of time-resolved proton radiography using x-ray flat-panel imaging system.

PubMed

Jee, K-W; Zhang, R; Bentefour, E H; Doolan, P J; Cascio, E; Sharp, G; Flanz, J; Lu, H-M

2017-03-07

Proton beam therapy benefits from the Bragg peak and delivers highly conformal dose distributions. However, the location of the end-of-range is subject to uncertainties related to the accuracy of the relative proton stopping power estimates and thereby the water-equivalent path length (WEPL) along the beam. To remedy the range uncertainty, an in vivo measurement of the WEPL through the patient, i.e. a proton-range radiograph, is highly desirable. Towards that goal, we have explored a novel method of proton radiography based on the time-resolved dose measured by a flat panel imager (FPI). A 226 MeV pencil beam and a custom-designed range modulator wheel (MW) were used to create a time-varying broad beam. The proton imaging technique used exploits this time dependency by looking at the dose rate at the imager as a function of time. This dose rate function (DRF) has a unique time-varying dose pattern at each depth of penetration. A relatively slow rotation of the MW (0.2 revolutions per second) and a fast image acquisition (30 frames per second, ~33 ms sampling) provided a sufficient temporal resolution for each DRF. Along with the high output of the CsI:Tl scintillator, imaging with pixel binning (2  ×  2) generated high signal-to-noise data at a very low radiation dose (~0.1 cGy). Proton radiographs of a head phantom and a Gammex CT calibration phantom were taken with various configurations. The results of the phantom measurements show that the FPI can generate low noise and high spatial resolution proton radiographs. The WEPL values of the CT tissue surrogate inserts show that the measured relative stopping powers are accurate to ~2%. The panel did not show any noticeable radiation damage after the accumulative dose of approximately 3831 cGy. In summary, we have successfully demonstrated a highly practical method of generating proton radiography using an x-ray flat panel imager.

Acoustic time-of-flight for proton range verification in water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Kevin C.; Avery, Stephen, E-mail: Stephen.A

2016-09-15

Purpose: Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. Methods: Gaussian-like proton pulses with 17 μs widths and instantaneous currents of 480 nA (5.6 × 10{sup 7} protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom,more » and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. Results: A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 10{sup 7} protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%–90% rise time of 11 μs. Simulation and experiment arrival times agreed well, and the observed 2.4 μs delay between simulation and experiment is attributed to the difference between the hydrophone’s acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (−2.0,  0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = − 4.5 mm and standard deviation = 2.0 mm. Conclusions: Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam’s position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 μs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.« less

Effects of Proton and Combined Proton and (56)Fe Radiation on the Hippocampus.

PubMed

Raber, Jacob; Allen, Antiño R; Sharma, Sourabh; Allen, Barrett; Rosi, Susanna; Olsen, Reid H J; Davis, Matthew J; Eiwaz, Massarra; Fike, John R; Nelson, Gregory A

2016-01-01

The space radiation environment contains protons and (56)Fe, which could pose a significant hazard to space flight crews during and after missions. The space environment involves complex radiation exposures, thus, the effects of a dose of protons might be modulated by a dose of heavy-ion radiation. The brain, and particularly the hippocampus, may be susceptible to space radiation-induced changes. In this study, we first determined the dose-response effect of proton radiation (150 MeV) on hippocampus-dependent cognition 1 and 3 months after exposure. Based on those results, we subsequently exposed mice to protons alone (150 MeV, 0.1 Gy), (56)Fe alone (600 MeV/n, 0.5 Gy) or combined proton and (56)Fe radiations (protons first) with the two exposures separated by 24 h. At one month postirradiation, all animal groups showed novel object recognition. However, at three months postirradiation, mice exposed to either protons or combined proton and (56)Fe radiations showed impaired novel object recognition, which was not observed in mice irradiated with (56)Fe alone. The mechanisms in these impairments might involve inflammation. In mice irradiated with protons alone or (56)Fe alone three months earlier, there was a negative correlation between a measure of novel object recognition and the number of newly born activated microglia in the dentate gyrus. Next, cytokine and chemokine levels were assessed in the hippocampus. At one month after exposure the levels of IL-12 were higher in mice exposed to combined radiations compared with sham-irradiated mice, while the levels of IFN-γ were lower in mice exposed to (56)Fe radiation alone or combined radiations. In addition, IL-4 levels were lower in (56)Fe-irradiated mice compared with proton-irradiated mice and TNF-α levels were lower in proton-irradiated mice than in mice receiving combined radiations. At three months after exposure, macrophage-derived chemokine (MDC) and eotaxin levels were lower in mice receiving combined radiations. The levels of MDC and eotaxin correlated and the levels of MDC, but not eotaxin, correlated with the percentage of newly born activated microglia in the blades of the dentate gyrus. Finally, hippocampal IL-6 levels were higher in mice receiving combined radiations compared with mice receiving (56)Fe radiation alone. These data demonstrate the sensitivity of novel object recognition for detecting cognitive injury three months after exposure to proton radiation alone, and combined exposure to proton and (56)Fe radiations, and that newly-born activated microglia and inflammation might be involved in this injury.

Acoustic time-of-flight for proton range verification in water.

PubMed

Jones, Kevin C; Vander Stappen, François; Sehgal, Chandra M; Avery, Stephen

2016-09-01

Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. Gaussian-like proton pulses with 17 μs widths and instantaneous currents of 480 nA (5.6 × 10(7) protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom, and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 10(7) protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%-90% rise time of 11 μs. Simulation and experiment arrival times agreed well, and the observed 2.4 μs delay between simulation and experiment is attributed to the difference between the hydrophone's acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (-2.0,  0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = - 4.5 mm and standard deviation = 2.0 mm. Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam's position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 μs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

PubMed Central

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm3, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

SU-E-T-764: Track Repeating Algorithm for Proton Therapy Applied to Intensity Modulated Proton Therapy for Head-And-Neck Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yepes, P; Mirkovic, D; Mohan, R

Purpose: To determine the suitability of fast Monte Carlo techniques for dose calculation in particle therapy based on track-repeating algorithm for Intensity Modulated Proton Therapy, IMPT. The application of this technique will make possible detailed retrospective studies of large cohort of patients, which may lead to a better determination of Relative Biological Effects from the analysis of patient data. Methods: A cohort of six head-and-neck patients treated at the University of Texas MD Anderson Cancer Center with IMPT were utilized. The dose distributions were calculated with the standard Treatment Plan System, TPS, MCNPX, GEANT4 and FDC, a fast track-repeating algorithmmore » for proton therapy for the verification and the patient plans. FDC is based on a GEANT4 database of trajectories of protons in a water. The obtained dose distributions were compared to each other utilizing the g-index criteria for 3mm-3% and 2mm-2%, for the maximum spatial and dose differences. The γ-index was calculated for voxels with a dose at least 10% of the maximum delivered dose. Dose Volume Histograms are also calculated for the various dose distributions. Results: Good agreement between GEANT4 and FDC is found with less than 1% of the voxels with a γ-index larger than 1 for 2 mm-2%. The agreement between MCNPX with FDC is within the requirements of clinical standards, even though it is slightly worse than the comparison with GEANT4.The comparison with TPS yielded larger differences, what is also to be expected because pencil beam algorithm do not always performed well in highly inhomogeneous areas like head-and-neck. Conclusion: The good agreement between a track-repeating algorithm and a full Monte Carlo for a large cohort of patients and a challenging, site like head-and-neck, opens the path to systematic and detailed studies of large cohorts, which may yield better understanding of biological effects.« less

The Node 1 (or Unity) Module for the International Space Station

NASA Technical Reports Server (NTRS)

1997-01-01

This photograph, taken by the Boeing Company,shows Boeing technicians preparing to install one of six hatches or doors to the Node 1 (also called Unity), the first U.S. Module for the International Space Station (ISS). The Node 1, or Unity, serves as a cornecting passageway to Space Station modules and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian-built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

The Node 1 (or Unity) Module for the International Space Station

NASA Technical Reports Server (NTRS)

1997-01-01

This photograph, taken by the Boeing Company, shows Boeing technicians preparing to install one of six hatches or doors to the Node 1 (also called Unity), the first U.S. Module for the International Space Station (ISS). The Node 1, or Unity, serves as a cornecting passageway to Space Station modules and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian-built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

The effects of gamma-ray irradiation on organic materials of different conjugation lengths

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Taylor, Edward W.

2009-08-01

The radiation resistance of organic electro-optic and optoelectronic materials of different conjugation lengths for space applications is receiving increased attention. Earlier investigation reported that guest-host (G-H) poled polymer EO modulator devices composed of a phenyltetraene bridge-type chromophore in amorphous polycarbonate (CLD/APC) did not exhibit a decrease in EO response (i.e., an increase in modulation-switching voltage- Vπ) following irradiation by low dose [10-160 krad(Si)] 60Co gamma-rays. In this work, the post-irradiation responses of 60Co gamma-rays on CLD1/APC thin films are examined by various chemical and spectroscopic methods including: a solubility test, thin-layer chromatography, proton nuclear magnetic resonance spectroscopy, UV-vis absorption, and infra-red absorption. The results indicate that CLD1 and APC did not decompose under gamma-ray irradiation at dose levels ranging from 66-274 krad(Si) and from 61-154 krad(Si), respectively which support the previously reported data. A comparison with an in situ proton irradiated DRI/PMMA material is also presented.

Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

PubMed

Unkelbach, Jan; Chan, Timothy C Y; Bortfeld, Thomas

2007-05-21

Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches--although conceptually different--yield very similar results on a qualitative level.

Reengineering cyt b562 for hydrogen production: A facile route to artificial hydrogenases.

PubMed

Sommer, Dayn Joseph; Vaughn, Michael David; Clark, Brett Colby; Tomlin, John; Roy, Anindya; Ghirlanda, Giovanna

2016-05-01

Bioinspired, protein-based molecular catalysts utilizing base metals at the active are emerging as a promising avenue to sustainable hydrogen production. The protein matrix modulates the intrinsic reactivity of organometallic active sites by tuning second-sphere and long-range interactions. Here, we show that swapping Co-Protoporphyrin IX for Fe-Protoporphyrin IX in cytochrome b562 results in an efficient catalyst for photoinduced proton reduction to molecular hydrogen. Further, the activity of wild type Co-cyt b562 can be modulated by a factor of 2.5 by exchanging the coordinating methionine with alanine or aspartic acid. The observed turnover numbers (TON) range between 125 and 305, and correlate well with the redox potential of the Co-cyt b562 mutants. The photosensitized system catalyzes proton reduction with high efficiency even under an aerobic atmosphere, implicating its use for biotechnological applications. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. Copyright © 2015 Elsevier B.V. All rights reserved.

Probabilistic Assessment of Radiation Risk for Astronauts in Space Missions

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; DeAngelis, Giovanni; Cucinotta, Francis A.

2009-01-01

Accurate predictions of the health risks to astronauts from space radiation exposure are necessary for enabling future lunar and Mars missions. Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons, (less than 100 MeV); and galactic cosmic rays (GCR), which include protons and heavy ions of higher energies. While the expected frequency of SPEs is strongly influenced by the solar activity cycle, SPE occurrences themselves are random in nature. A solar modulation model has been developed for the temporal characterization of the GCR environment, which is represented by the deceleration potential, phi. The risk of radiation exposure from SPEs during extra-vehicular activities (EVAs) or in lightly shielded vehicles is a major concern for radiation protection, including determining the shielding and operational requirements for astronauts and hardware. To support the probabilistic risk assessment for EVAs, which would be up to 15% of crew time on lunar missions, we estimated the probability of SPE occurrence as a function of time within a solar cycle using a nonhomogeneous Poisson model to fit the historical database of measurements of protons with energy > 30 MeV, (phi)30. The resultant organ doses and dose equivalents, as well as effective whole body doses for acute and cancer risk estimations are analyzed for a conceptual habitat module and a lunar rover during defined space mission periods. This probabilistic approach to radiation risk assessment from SPE and GCR is in support of mission design and operational planning to manage radiation risks for space exploration.

Observations of the SAA radiation distribution by Liulin-E094 instrument on ISS

NASA Astrophysics Data System (ADS)

Dachev, Tsvetan; Atwell, William; Semones, Edward; Tomov, Borislav; Reddell, Brandon

Space radiation measurements were made on the International Space Station (ISS) with the Bulgarian Liulin-E094 instrument, which contains 4 Mobile Dosimetry Units (MDU), and the NASA Tissue Equivalent Proportional Counter (TEPC) during the time period May 11-July 26, 2001. In the time span 11-27 May 2001 four MDUs were placed at fixed locations: one unit (MDU #1) in the ISS "Unity" Node-1 and three (MDU #2-#4) units were located in the US Laboratory module. The MDU #2 and the TEPC were located in the US Laboratory module Human Research Facility (rack #1, port side). In this paper we discuss the flight observed asymmetries in different detectors on the ascending and descending parts of the ISS orbits. The differences are described by the shielding differences generated by different geometry between the predominating eastward drifting protons and the orientation and placement of the MDUs within the ISS. Shielding distributions were generated for the combined ISS and detector shielding models. The AP8MAX and AE8MAX trapped radiation models were used to compute the daily absorbed dose for the five detectors and are compared with the flight measurements. In addition, the trapped proton incident spectra inside of ISS were calculated using calibration curve of MDU obtained during the tests with protons at the Louvain-la-Neuve cyclotron facility. The energy of incident spectra maximums were analyzed against L value for the individual passes through the South Atlantic Anomaly.

In-treatment tests for the monitoring of proton and carbon-ion therapy with a large area PET system at CNAO

NASA Astrophysics Data System (ADS)

Rosso, V.; Battistoni, G.; Belcari, N.; Camarlinghi, N.; Ciocca, M.; Collini, F.; Ferretti, S.; Kraan, A. C.; Lucenò, S.; Molinelli, S.; Pullia, M.; Sportelli, G.; Zaccaro, E.; Del Guerra, A.

2016-07-01

One of the most promising new radiotherapy techniques makes use of charged particles like protons and carbon ions, rather than photons. At present, there are more than 50 particle therapy centers operating worldwide, and many new centers are being constructed. Positron Emission Tomography (PET) is considered a well-established non-invasive technique to monitor range and delivered dose in patients treated with particle therapy. Nuclear interactions of the charged hadrons with the patient tissue lead to the production of β+ emitting isotopes (mainly 15O and 11C), that decay with a short lifetime producing a positron. The two 511 keV annihilation photons can be detected with a PET detector. In-beam PET is particularly interesting because it could allow monitoring the ions range also during dose delivery. A large area dual head PET prototype was built and tested. The system is based on an upgraded version of the previously developed DoPET prototype. Each head covers now 15×15 cm2 and is composed by 9 (3×3) independent modules. Each module consists of a 23×23 LYSO crystal matrix (2 mm pitch) coupled to H8500 PMT and is readout by custom front-end and a FPGA based data acquisition electronics. Data taken at the CNAO treatment facility in Pavia with proton and carbon beams impinging on heterogeneous phantoms demonstrate the DoPET capability to detect the presence of a small air cavity in the phantom.

HelMod in the Works: From Direct Observations to the Local Interstellar Spectrum of Cosmic-Ray Electrons

NASA Astrophysics Data System (ADS)

Boschini, M. J.; Della Torre, S.; Gervasi, M.; Grandi, D.; Jóhannesson, G.; La Vacca, G.; Masi, N.; Moskalenko, I. V.; Pensotti, S.; Porter, T. A.; Quadrani, L.; Rancoita, P. G.; Rozza, D.; Tacconi, M.

2018-02-01

The local interstellar spectrum (LIS) of cosmic-ray (CR) electrons for the energy range 1 MeV to 1 TeV is derived using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HELMOD, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HELMOD, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The optimized HelMod parameters are then used to adjust GALPROP parameters to predict a refined LIS with the procedure repeated subject to a convergence criterion. The parameter optimization uses an extensive data set of proton spectra from 1997 to 2015. The proposed CR electron LIS accommodates both the low-energy interstellar spectra measured by Voyager 1 as well as the high-energy observations by PAMELA and AMS-02 that are made deep in the heliosphere; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The interstellar and heliospheric propagation parameters derived in this study agree well with our earlier results for CR protons, helium nuclei, and anti-protons propagation and LIS obtained in the same framework.

Poster - 40: Treatment Verification of a 3D-printed Eye Phantom for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunning, Chelsea; Lindsay, Clay; Unick, Nick

Purpose: Ocular melanoma is a form of eye cancer which is often treated using proton therapy. The benefit of the steep proton dose gradient can only be leveraged for accurate patient eye alignment. A treatment-planning program was written to plan on a 3D-printed anatomical eye-phantom, which was then irradiated to demonstrate the feasibility of verifying in vivo dosimetry for proton therapy using PET imaging. Methods: A 3D CAD eye model with critical organs was designed and voxelized into the Monte-Carlo transport code FLUKA. Proton dose and PET isotope production were simulated for a treatment plan of a test tumour, generatedmore » by a 2D treatment-planning program developed using NumPy and proton range tables. Next, a plastic eye-phantom was 3D-printed from the CAD model, irradiated at the TRIUMF Proton Therapy facility, and imaged using a PET scanner. Results: The treatment-planning program prediction of the range setting and modulator wheel was verified in FLUKA to treat the tumour with at least 90% dose coverage for both tissue and plastic. An axial isotope distribution of the PET isotopes was simulated in FLUKA and converted to PET scan counts. Meanwhile, the 3D-printed eye-phantom successfully yielded a PET signal. Conclusions: The 2D treatment-planning program can predict required parameters to sufficiently treat an eye tumour, which was experimentally verified using commercial 3D-printing hardware to manufacture eye-phantoms. Comparison between the simulated and measured PET isotope distribution could provide a more realistic test of eye alignment, and a variation of the method using radiographic film is being developed.« less

Results of a multicentric in silico clinical trial (ROCOCO): comparing radiotherapy with photons and protons for non-small cell lung cancer.

PubMed

Roelofs, Erik; Engelsman, Martijn; Rasch, Coen; Persoon, Lucas; Qamhiyeh, Sima; de Ruysscher, Dirk; Verhaegen, Frank; Pijls-Johannesma, Madelon; Lambin, Philippe

2012-01-01

This multicentric in silico trial compares photon and proton radiotherapy for non-small cell lung cancer patients. The hypothesis is that proton radiotherapy decreases the dose and the volume of irradiated normal tissues even when escalating to the maximum tolerable dose of one or more of the organs at risk (OAR). Twenty-five patients, stage IA-IIIB, were prospectively included. On 4D F18-labeled fluorodeoxyglucose-positron emission tomography-computed tomography scans, the gross tumor, clinical and planning target volumes, and OAR were delineated. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) photon and passive scattered conformal proton therapy (PSPT) plans were created to give 70 Gy to the tumor in 35 fractions. Dose (de-)escalation was performed by rescaling to the maximum tolerable dose. Protons resulted in the lowest dose to the OAR, while keeping the dose to the target at 70 Gy. The integral dose (ID) was higher for 3DCRT (59%) and IMRT (43%) than for PSPT. The mean lung dose reduced from 18.9 Gy for 3DCRT and 16.4 Gy for IMRT to 13.5 Gy for PSPT. For 10 patients, escalation to 87 Gy was possible for all 3 modalities. The mean lung dose and ID were 40 and 65% higher for photons than for protons, respectively. The treatment planning results of the Radiation Oncology Collaborative Comparison trial show a reduction of ID and the dose to the OAR when treating with protons instead of photons, even with dose escalation. This shows that PSPT is able to give a high tumor dose, while keeping the OAR dose lower than with the photon modalities.

The University of Texas M.D. Anderson Cancer Center Proton Therapy Facility

NASA Astrophysics Data System (ADS)

Smith, Alfred; Newhauser, Wayne; Latinkic, Mitchell; Hay, Amy; McMaken, Bruce; Styles, John; Cox, James

2003-08-01

The University of Texas M.D. Anderson Cancer Center (MDACC), in partnership with Sanders Morris Harris Inc., a Texas-based investment banking firm, and The Styles Company, a developer and manager of hospitals and healthcare facilities, is building a proton therapy facility near the MDACC main complex at the Texas Medical Center in Houston, Texas USA. The MDACC Proton Therapy Center will be a freestanding, investor-owned radiation oncology center offering state-of-the-art proton beam therapy. The facility will have four treatment rooms: three rooms will have rotating, isocentric gantries and the fourth treatment room will have capabilities for both large and small field (e.g. ocular melanoma) treatments using horizontal beam lines. There will be an additional horizontal beam room dedicated to physics research and development, radiation biology research, and outside users who wish to conduct experiments using proton beams. The first two gantries will each be initially equipped with a passive scattering nozzle while the third gantry will have a magnetically swept pencil beam scanning nozzle. The latter will include enhancements to the treatment control system that will allow for the delivery of proton intensity modulation treatments. The proton accelerator will be a 250 MeV zero-gradient synchrotron with a slow extraction system. The facility is expected to open for patient treatments in the autumn of 2005. It is anticipated that 675 patients will be treated during the first full year of operation, while full capacity, reached in the fifth year of operation, will be approximately 3,400 patients per year. Treatments will be given up to 2-shifts per day and 6 days per week.

Feasibility Study of Glass Dosimeter for In Vivo Measurement: Dosimetric Characterization and Clinical Application in Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rah, Jeong-Eun; Oh, Do Hoon; Kim, Jong Won

Purpose: To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. Methods and Materials: The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with amore » varying separation between the target volume and the surface of 6 patients. Results and Discussion: Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatment planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. Conclusion: It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry.« less

Feasibility study of glass dosimeter for in vivo measurement: dosimetric characterization and clinical application in proton beams.

PubMed

Rah, Jeong-Eun; Oh, Do Hoon; Kim, Jong Won; Kim, Dae-Hyun; Suh, Tae-Suk; Ji, Young Hoon; Shin, Dongho; Lee, Se Byeong; Kim, Dae Yong; Park, Sung Yong

2012-10-01

To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with a varying separation between the target volume and the surface of 6 patients. Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatment planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry. Copyright © 2012 Elsevier Inc. All rights reserved.

Shocklike soliton because of an impinge of protons and electrons solar particles with Venus ionosphere

NASA Astrophysics Data System (ADS)

Moslem, W. M.; Rezk, S.; Abdelsalam, U. M.; El-Labany, S. K.

2018-04-01

This paper introduces an investigation of shocklike soliton or small amplitude Double Layers (DLs) in a collisionless plasma, consisting of positive and negative ions, nonthermal electrons, as well as solar wind streaming protons and electrons. Gardner equation is derived and its shocklike soliton solution is obtained. The model is employed to recognize a possible nonlinear wave at Venus ionosphere. The results indicate that the number densities and velocities of the streaming particles play crucial role to determine the polarity and characteristic features (amplitude and width) of the shocklike soliton waves. An electron streaming speed modifies a negative shocklike wave profile, while an ion streaming speed modulates a positive shocklike wave characteristic.

Development of a center for light ion therapy and accurate tumor diagnostics at karolinska institutet and hospital

NASA Astrophysics Data System (ADS)

Brahme, Anders; Lind, Bengt K.

2002-04-01

Radiation therapy is today in a state of very rapid development with new intensity modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumors of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new center for ion therapy and tumor diagnostics in Stockholm is to develop radiobiologically optimized 3-dimensional pencil beam scanning techniques. Beside the "classical" approaches using low ionization density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose high-precision "boost" treatment with carbon or oxygen ions during one week preceding the final treatment with conventional radiations in the referring hospital. The rationale behind these approaches is to reduce the high ionization density dose to the normal tissue stroma inside the tumor and to ensure a microscopically uniform dose delivery. The principal idea of the center is to closely integrate ion therapy into the clinical routine and research of a large radiotherapy department. The light ion therapy center will therefore be combined with advanced tumor diagnostics including MR and PET-CT imaging to facilitate efficient high-precision high-dose boost treatment of remitted patients. The possibility to do 3D tumor diagnostics and 3D dose delivery verification with the same PET camera will be the ultimate step in high quality adaptive radiation therapy where alterations in the delivered dose can be corrected by subsequent treatments

Proton modulation of recombinant GABAA receptors: influence of GABA concentration and the β subunit TM2–TM3 domain

PubMed Central

Wilkins, Megan E; Hosie, Alastair M; Smart, Trevor G

2005-01-01

Regulation of GABAA receptors by extracellular pH exhibits a dependence on the receptor subunit composition. To date, the molecular mechanism responsible for the modulation of GABAA receptors at alkaline pH has remained elusive. We report here that the GABA-activated current can be potentiated at pH 8.4 for both αβ and αβγ subunit-containing receptors, but only at GABA concentrations below the EC40. Site-specific mutagenesis revealed that a single lysine residue, K279 in the β subunit TM2–TM3 linker, was critically important for alkaline pH to modulate the function of both α1β2 and α1β2γ2 receptors. The ability of low concentrations of GABA to reveal different pH titration profiles for GABAA receptors was also examined at acidic pH. At pH 6.4, GABA activation of αβγ receptors was enhanced at low GABA concentrations. This effect was ablated by the mutation H267A in the β subunit. Decreasing the pH further to 5.4 inhibited GABA responses via αβγ receptors, whereas those responses recorded from αβ receptors were potentiated. Inserting homologous β subunit residues into the γ2 subunit to recreate, in αβγ receptors, the proton modulatory profile of αβ receptors, established that in the presence of β2H267, the mutation γ2T294K was necessary to potentiate the GABA response at pH 5.4. This residue, T294, is homologous to K279 in the β subunit and suggests that a lysine at this position is an important residue for mediating the allosteric effects of both acidic and alkaline pH changes, rather than forming a direct site for protonation within the GABAA receptor. PMID:15946973

A thermo-physical analysis of the proton pump vacuolar-ATPase: the constructal approach.

PubMed

Lucia, Umberto; Ponzetto, Antonio; Deisboeck, Thomas S

2014-10-24

Pumping protons across a membrane was a critical step at the origin of life on earth, and it is still performed in all living organisms, including in human cells. Proton pumping is paramount to keep normal cells alive, e.g. for lysosomal digestion and for preparing peptides for immune recognition, but it goes awry in cancer cells. They acidify their microenvironment hence membrane voltage is lowered, which in turn induces cell proliferation, a hallmark of cancer. Proton pumping is achieved by means of rotary motors, namely vacuolar ATPases (V-ATPase), which are present at many of the multiple cellular interfaces. Therefore, we undertook an examination of the thermodynamic properties of V-ATPases. The principal result is that the V-ATPase-mediated control of the cell membrane potential and the related and consequent environmental pH can potentially represent a valuable support strategy for anticancer therapies. A constructal theory approach is used as a new viewpoint to study how V-ATPase can be modulated for therapeutic purposes. In particular, V-ATPase can be regulated by using external fields, such as electromagnetic fields, and a theoretical approach has been introduced to quantify the appropriate field strength and frequency for this new adjuvant therapeutic strategy.

Protective effects of dietary antioxidants on proton total-body irradiation-mediated hematopoietic cell and animal survival.

PubMed

Wambi, Chris O; Sanzari, Jenine K; Sayers, Carly M; Nuth, Manunya; Zhou, Zhaozong; Davis, James; Finnberg, Niklas; Lewis-Wambi, Joan S; Ware, Jeffrey H; El-Deiry, Wafik S; Kennedy, Ann R

2009-08-01

Abstract Dietary antioxidants have radioprotective effects after gamma-radiation exposure that limit hematopoietic cell depletion and improve animal survival. The purpose of this study was to determine whether a dietary supplement consisting of l-selenomethionine, vitamin C, vitamin E succinate, alpha-lipoic acid and N-acetyl cysteine could improve survival of mice after proton total-body irradiation (TBI). Antioxidants significantly increased 30-day survival of mice only when given after irradiation at a dose less than the calculated LD(50/30); for these data, the dose-modifying factor (DMF) was 1.6. Pretreatment of animals with antioxidants resulted in significantly higher serum total white blood cell, polymorphonuclear cell and lymphocyte cell counts at 4 h after 1 Gy but not 7.2 Gy proton TBI. Antioxidants significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGFbeta1 and increased bone marrow cell counts and spleen mass after TBI. Maintenance of the antioxidant diet resulted in improved recovery of peripheral leukocytes and platelets after sublethal and potentially lethal TBI. Taken together, oral supplementation with antioxidants appears to be an effective approach for radioprotection of hematopoietic cells and improvement of animal survival after proton TBI.

SU-E-T-105: Development of 3D Dose Verification System for Volumetric Modulated Arc Therapy Using Improved Polyacrylamide-Based Gel Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, K; Fujimoto, S; Akagi, Y

2014-06-01

Purpose: The aim of this dosimetric study was to develop 3D dose verification system for volumetric modulated arc therapy (VMAT) using polyacrylamide-based gel (PAGAT) dosimeter improved the sensitivity by magnesium chloride (MgCl{sub 2}). Methods: PAGAT gel containing MgCl{sub 2} as a sensitizer was prepared in this study. Methacrylic-acid-based gel (MAGAT) was also prepared to compare the dosimetric characteristics with PAGAT gel. The cylindrical glass vials (4 cm diameter, 12 cm length) filled with each polymer gel were irradiated with 6 MV photon beam using Novalis Tx linear accelerator (Varian/BrainLAB). The irradiated polymer gel dosimeters were scanned with Signa 1.5 Tmore » MRI system (GE), and dose calibration curves were obtained using T{sub 2} relaxation rate (R{sub 2} = 1/T{sub 2}). Dose rate (100-600 MU min{sup −1}) and fractionation (1-8 fractions) were varied. In addition, a cubic acrylic phantom (10 × 10 × 10 cm{sup 3}) filled with improved PAGAT gel inserted into the IMRT phantom (IBA) was irradiated with VMAT (RapidArc). C-shape structure was used for the VMAT planning by the Varian Eclipse treatment planning system (TPS). The dose comparison of TPS and measurements with the polymer gel dosimeter was accomplished by the gamma index analysis, overlaying the dose profiles for a set of data on selected planes using in-house developed software. Results: Dose rate and fractionation dependence of improved PAGAT gel were smaller than MAGAT gel. A high similarity was found by overlaying the dose profiles measured with improved PAGAT gel dosimeter and the TPS dose, and the mean pass rate of the gamma index analysis using 3%/3 mm criteria was achieved 90% on orthogonal planes for VMAT using improved PAGAT gel dosimeter. Conclusion: In-house developed 3D dose verification system using improved polyacrylamide-based gel dosimeter had a potential as an effective tool for VMAT QA.« less

SU-F-T-388: Comparison of Biophysical Indices in Hippocampal-Avoidance Whole Brain VMAT and IMRT Radiation Therapy Treatment Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kendall, E; Ahmad, S; Algan, O

2016-06-15

Purpose: To compare biophysical indices of Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) treatment plans for whole brain radiation therapy following the NRG-CC001 protocol. Methods: In this retrospective study, a total of fifteen patients were planned with Varian Eclipse Treatment Planning System using VMAT (RapidArc) and IMRT techniques. The planning target volume (PTV) was defined as the whole brain volume excluding a uniform three-dimensional 5mm expansion of the hippocampus volume. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 95% of the target volume receiving 100% of themore » prescribed dose. The NRG Oncology protocol guidelines were followed for contouring and dose-volume constraints. A single radiation oncologist evaluated all treatment plans. Calculations of statistical significance were performed using Student’s paired t-test. Results: All VMAT and IMRT plans met the NRG-CC001 protocol dose-volume criteria. The average equivalent uniform dose (EUD) for the PTV for VMAT vs. IMRT was respectively (19.05±0.33 Gy vs. 19.38±0.47 Gy) for α/β of 2 Gy and (19.47±0.30 Gy vs. 19.84±0.42 Gy) for α/β of 10 Gy. For the PTV, the average mean and maximum doses were 2% and 5% lower in VMAT plans than in IMRT plans, respectively. The average EUD and the normal tissue complication probability (NTCP) for the hippocampus in VMAT vs. IMRT plans were (15.28±1.35 Gy vs. 15.65±0.99 Gy, p=0.18) and (0.305±0.012 Gy vs. 0.308±0.008 Gy, p=0.192), respectively. The average EUD and NTCP for the optic chiasm were both 2% higher in VMAT than in IMRT plans. Conclusion: Though statistically insignificant, VMAT plans indicate a lower hippocampus EUD than IMRT plans. Also, a small variation in NTCP was found between plans.« less

SU-E-T-269: Quality Assurance of Spine Volumetric Modulated Arc Therapy with Flattening Filter Free Beams Using Gafchromic EBT3 Films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Y; Cho, B; Kwak, J

2014-06-01

Purpose: We implemented the Gafchromic film-based patient specific QA of volumetric modulated arc therapy (VMAT) with flattening-filter free (FFF) beams for spine metastases and validated the accuracy of fast arc delivery. Methods: EBT3 films and a homemade cylindrical QA phantom were employed for dosimetric verification of VMATs. For 14 FFF VMAT plans (10 with 10-MV FFF beams and 4 with 6-MV FFF beams), the doses were recalculated on the phantom and delivered by a TrueBeam STx accelerator equipped with a high-definition 120 leaf MLC. The EBT3 films were scanned using an Epson 10000XL scanner through the FilmQA Pro software. Allmore » the irradiated film images were converted to dose map using a calibration response curve. The resulting dose map of film measurement was compared with treatment plan and evaluated using gamma analysis with dose tolerance of 2% within 2 mm. In addition, the point-dose measurement in the phantom using an ion chamber was evaluated as a reference in a ratio of measured and planned doses. Results: The gamma pass rates averaged over all FFF plans for composite-field measurements were 96.0 ± 3.6% (88.9%–99.5%). When adopting a tolerance level of 3% - 3 mm, the gamma pass rates were improved with the ranges from 98% to 100%. In addition, dose profiles and dose distributions showed that spinal cord was protected by the rapid dose fall-off and by delivering the treatment with high precision. In point-dose measurements, the average differences between the measured and planned doses were 0.5% ± 1.0% of the prescription dose. Conclusion: We demonstrated that Gafchromic EBT3 film would be an effective patient-specific QA tool, especially for VMAT of spine SBRT with treatment of small fields and highly gradient dose distributions. The results of film QA verified that the dosimetric accuracy of spine SBRT utilizing RapidArc with FFF beams in our institution is reliable.« less

Prostate volumetric‐modulated arc therapy: dosimetry and radiobiological model variation between the single‐arc and double‐arc technique

PubMed Central

Jiang, Runqing

2013-01-01

This study investigates the dosimetry and radiobiological model variation when a second photon arc was added to prostate volumetric‐modulated arc therapy (VMAT) using the single‐arc technique. Dosimetry and radiobiological model comparison between the single‐arc and double‐arc prostate VMAT plans were performed on five patients with prostate volumes ranging from 29−68.1 cm3. The prescription dose was 78 Gy/39 fractions and the photon beam energy was 6 MV. Dose‐volume histogram, mean and maximum dose of targets (planning and clinical target volume) and normal tissues (rectum, bladder and femoral heads), dose‐volume criteria in the treatment plan (D99% of PTV; D30%,D50%,V17Gy and V35Gy of rectum and bladder; D5% of femoral heads), and dose profiles along the vertical and horizontal axis crossing the isocenter were determined using the single‐arc and double‐arc VMAT technique. For comparison, the monitor unit based on the RapidArc delivery method, prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman‐Burman‐Kutcher algorithm were calculated. It was found that though the double‐arc technique required almost double the treatment time than the single‐arc, the double‐arc plan provided a better rectal and bladder dose‐volume criteria by shifting the delivered dose in the patient from the anterior–posterior direction to the lateral. As the femoral head was less radiosensitive than the rectum and bladder, the double‐arc technique resulted in a prostate VMAT plan with better prostate coverage and rectal dose‐volume criteria compared to the single‐arc. The prostate TCP of the double‐arc plan was found slightly increased (0.16%) compared to the single‐arc. Therefore, when the rectal dose‐volume criteria are very difficult to achieve in a single‐arc prostate VMAT plan, it is worthwhile to consider the double‐arc technique. PACS number: 87.55.D‐, 87.55.dk, 87.55.K‐, 87.55.Qr

SU-C-207A-01: A Novel Maximum Likelihood Method for High-Resolution Proton Radiography/proton CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins-Fekete, C; Centre Hospitalier University de Quebec, Quebec, QC; Mass General Hospital

2016-06-15

Purpose: Multiple Coulomb scattering is the largest contributor to blurring in proton imaging. Here we tested a maximum likelihood least squares estimator (MLLSE) to improve the spatial resolution of proton radiography (pRad) and proton computed tomography (pCT). Methods: The object is discretized into voxels and the average relative stopping power through voxel columns defined from the source to the detector pixels is optimized such that it maximizes the likelihood of the proton energy loss. The length spent by individual protons in each column is calculated through an optimized cubic spline estimate. pRad images were first produced using Geant4 simulations. Anmore » anthropomorphic head phantom and the Catphan line-pair module for 3-D spatial resolution were studied and resulting images were analyzed. Both parallel and conical beam have been investigated for simulated pRad acquisition. Then, experimental data of a pediatric head phantom (CIRS) were acquired using a recently completed experimental pCT scanner. Specific filters were applied on proton angle and energy loss data to remove proton histories that underwent nuclear interactions. The MTF10% (lp/mm) was used to evaluate and compare spatial resolution. Results: Numerical simulations showed improvement in the pRad spatial resolution for the parallel (2.75 to 6.71 lp/cm) and conical beam (3.08 to 5.83 lp/cm) reconstructed with the MLLSE compared to averaging detector pixel signals. For full tomographic reconstruction, the improved pRad were used as input into a simultaneous algebraic reconstruction algorithm. The Catphan pCT reconstruction based on the MLLSE-enhanced projection showed spatial resolution improvement for the parallel (2.83 to 5.86 lp/cm) and conical beam (3.03 to 5.15 lp/cm). The anthropomorphic head pCT displayed important contrast gains in high-gradient regions. Experimental results also demonstrated significant improvement in spatial resolution of the pediatric head radiography. Conclusion: The proposed MLLSE shows promising potential to increase the spatial resolution (up to 244%) in proton imaging.« less

Protonation-modulated localization of excess electrons in histidine aqueous solutions revealed by ab initio molecular dynamics simulations: anion-centered versus cation-centered localization.

PubMed

Gao, Liang; Bu, Yuxiang

2017-05-31

In this work, we present an ab initio molecular dynamics simulation study on the interaction of an excess electron (EE) with histidine in its aqueous solution. Two different configurations of histidine (imidazole group protonated or not) are considered to reflect its different existing forms in neutral or slightly acidic surroundings. The simulation results indicate that localizations of EEs in different aqueous histidine solutions are quite different and are strongly affected by protonation of the side chain imidazole group and are thus pH-controlled. In neutral aqueous histidine solution, an EE localizes onto the carboxyl anionic group of the amino acid backbone after a relatively lengthy diffuse state, performing just like in an aliphatic amino acid solution. But in weakly acidic solution in which the side chain imidazole group is protonated, an EE undergoes a short lifetime diffuse state and finally localizes on the protonated imidazole group. We carefully examine these two different localization dynamics processes and analyze the competition between different dominating groups in their corresponding electron localization mechanisms. To explain the difference, we investigate the frontier molecular orbitals of these two systems and find that their energy levels and compositions are important to determine these differences. These findings can provide helpful information to understand the interaction mechanisms of low energy EEs with amino acids and even oligopeptides, especially with aromatic rings.

The role of merged interaction regions and drafts in the heliospheric modulation of cosmic rays beyond 20 AU - A computer simulation

NASA Technical Reports Server (NTRS)

Potgieter, M. S.; Le Roux, J. A.; Burlaga, L. F.; Mcdonald, F. B.

1993-01-01

Voyager 2 magnetic field measurements are used to simulate merged interaction and rarefaction regions (MIRs and RRs) for 1985-1989 via numerical solutions of the time-dependent, axially symmetric transport equation of cosmic rays in the heliosphere, together with the concurrent use of the wavy neutral sheet as a time-dependent drift parameter. This drift approach was found to be more successful, because it was able to reproduce the intensity levels, the factor modulation, and latitudinal gradients for 1 GeV protons at 23 AU.

Advances in radiation oncology for the management of oropharyngeal tumors.

PubMed

Gunn, G Brandon; Frank, Steven J

2013-08-01

The major benefits of modern radiation therapy (eg, intensity-modulated [x-ray] radiation therapy [IMRT]) for oropharyngeal cancer are reduced xerostomia and better quality of life. Intensity-modulated proton therapy may provide additional advantages over IMRT by reducing radiation beam-path toxicities. Several acute and late treatment-related toxicities and symptom constellations must be kept in mind when designing and comparing future treatment strategies, particularly because currently most patients with oropharyngeal carcinoma present with human papillomavirus-positive disease and are expected to have a high probability of long-term survival after treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

In Vivo Assessment of Neurotransmitters and Modulators with Magnetic Resonance Spectroscopy: Application to Schizophrenia

PubMed Central

Wijtenburg, S. Andrea; Yang, Shaolin; Fischer, Bernard A.; Rowland, Laura M.

2015-01-01

In vivo measurement of neurotransmitters and modulators is now feasible with advanced proton magnetic resonance spectroscopy (1H-MRS) techniques. This review provides a basic tutorial of MRS, describes the methods available to measure brain glutamate, glutamine, γ-aminobutyric acid, glutathione, N-acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3Tesla or higher, and summarizes the neurochemical findings in schizophrenia. Overall, 1H-MRS holds great promise for producing biomarkers that can serve as treatment targets, prediction of disease onset, or illness exacerbation in schizophrenia and other brain diseases. PMID:25614132

Revisit of cosmic ray antiprotons from dark matter annihilation with updated constraints on the background model from AMS-02 and collider data

NASA Astrophysics Data System (ADS)

Cui, Ming-Yang; Pan, Xu; Yuan, Qiang; Fan, Yi-Zhong; Zong, Hong-Shi

2018-06-01

We study the cosmic ray antiprotons with updated constraints on the propagation, proton injection, and solar modulation parameters based on the newest AMS-02 data near the Earth and Voyager data in the local interstellar space, and on the cross section of antiproton production due to proton-proton collisions based on new collider data. We use a Bayesian approach to properly consider the uncertainties of the model predictions of both the background and the dark matter (DM) annihilation components of antiprotons. We find that including an extra component of antiprotons from the annihilation of DM particles into a pair of quarks can improve the fit to the AMS-02 antiproton data considerably. The favored mass of DM particles is about 60~100 GeV, and the annihilation cross section is just at the level of the thermal production of DM (langleσvrangle ~ O(10‑26) cm3 s‑1).

The BESS Program

NASA Technical Reports Server (NTRS)

Mitchell, J. W.; Abe, K.; Anraku, K.; Fuke, H.; Haino, S.; Hams, T.; Imori, M.; Itazaki, A.; Izumi, K.; Kumazawa, T.

2004-01-01

In nine flights between 1993 and 2002, the Balloon Borne Experiment with a Superconducting Spectrometer (BESS) has measured the energy spectrum of cosmic-ray antiprotons between 0.18 and 4.20 GeV, and the spectra of protons and helium to several hundred GeV. BESS has also placed stringent upper limits on the existence of antihelium and antiduterons. Above about 1 GeV, models in which antiprotons are secondary products of the interactions of primary cosmic rays with the ISM agree with the BESS spectrum. Below 1 GeV, BESS data suggest the presence of an additional source of antiprotons. The antiproton/proton ratios measured between 1993 and 1999, during the Sun's positive-polarity phase, are consistent with simple models of solar modulation. Results from the 2000 flight, following the solar magnetic field reversal, show a sudden increase in the antiproton/proton ratio and tend to favor a charge-sign-dependent drift model. To extend BESS measurements to lower energies, a new instrument, BESS-Polar, is under construction for a flight from Antarctica in 2004.

Non-catalytic hydrogenation of VO2 in acid solution.

PubMed

Chen, Yuliang; Wang, Zhaowu; Chen, Shi; Ren, Hui; Wang, Liangxin; Zhang, Guobin; Lu, Yalin; Jiang, Jun; Zou, Chongwen; Luo, Yi

2018-02-26

Hydrogenation is an effective way to tune the property of metal oxides. It can conventionally be performed by doping hydrogen into solid materials with noble-metal catalysis, high-temperature/pressure annealing treatment, or high-energy proton implantation in vacuum condition. Acid solution naturally provides a rich proton source, but it should cause corrosion rather than hydrogenation to metal oxides. Here we report a facile approach to hydrogenate monoclinic vanadium dioxide (VO 2 ) in acid solution at ambient condition by placing a small piece of low workfunction metal (Al, Cu, Ag, Zn, or Fe) on VO 2 surface. It is found that the attachment of a tiny metal particle (~1.0 mm) can lead to the complete hydrogenation of an entire wafer-size VO 2 (>2 inch). Moreover, with the right choice of the metal a two-step insulator-metal-insulator phase modulation can even be achieved. An electron-proton co-doping mechanism has been proposed and verified by the first-principles calculations.

Generic FPGA-Based Platform for Distributed IO in Proton Therapy Patient Safety Interlock System

NASA Astrophysics Data System (ADS)

Eichin, Michael; Carmona, Pablo Fernandez; Johansen, Ernst; Grossmann, Martin; Mayor, Alexandre; Erhardt, Daniel; Gomperts, Alexander; Regele, Harald; Bula, Christian; Sidler, Christof

2017-06-01

At the Paul Scherrer Institute (PSI) in Switzerland, cancer patients are treated with protons. Proton therapy at PSI has a long history and started in the 1980s. More than 30 years later, a new gantry has recently been installed in the existing facility. This new machine has been delivered by an industry partner. A big challenge is the integration of the vendor's safety system into the existing PSI environment. Different interface standards and the complexity of the system made it necessary to find a technical solution connecting an industry system to the existing PSI infrastructure. A novel very flexible distributed IO system based on field-programmable gate array (FPGA) technology was developed, supporting many different IO interface standards and high-speed communication links connecting the device to a PSI standard versa module eurocard-bus input output controller. This paper summarizes the features of the hardware technology, the FPGA framework with its high-speed communication link protocol, and presents our first measurement results.

Emission switching of 4,6-diphenylpyrimidones: solvent and solid state effects.

PubMed

Adjaye-Mensah, Edward; Gonzalez, Walter G; Bussé, David R; Captain, Burjor; Miksovska, Jaroslava; Wilson, James N

2012-08-30

The photophysics of 1-ethyl-4,6-bis(4-methoxyphenyl)-2(1H)-pyrimidone (1) and 1-ethyl-4,6-bis(4-(dimethylamino)phenyl)-2(1H)-pyrimidone (2) were investigated to determine the mechanisms of emission switching in response to protonation. UV-vis and steady state emission spectroscopy of the protonated and unprotonated forms across a range of solvents reveal the polarity dependence of the vertical excitation energies. Emission lifetimes and quantum yields show the solvent dependency of the excited states. Emission enhancements were observed in polyethylene glycol solutions and in the solid state (both thin film and single crystal), demonstrating the role of intramolecular rotation in thermal relaxation of the excited states. TD-DFT calculations provide insights into the excited state geometries and the role of intramolecular charge transfer. The collected data show that emission of diphenylpyrimidones can be modulated by four factors, including the identity of the electron-donating auxochrome, protonation state, solvent polarity, and viscosity.

COMPARISON OF RESPONSE OF PASSIVE DOSIMETRY SYSTEMS IN SCANNING PROTON RADIOTHERAPY-A STUDY USING PAEDIATRIC ANTHROPOMORPHIC PHANTOMS.

PubMed

Kneževic, Ž; Ambrozova, I; Domingo, C; De Saint-Hubert, M; Majer, M; Martínez-Rovira, I; Miljanic, S; Mojzeszek, N; Porwol, P; Ploc, O; Romero-Expósito, M; Stolarczyk, L; Trinkl, S; Harrison, R M; Olko, P

2017-11-18

Proton beam therapy has advantages in comparison to conventional photon radiotherapy due to the physical properties of proton beams (e.g. sharp distal fall off, adjustable range and modulation). In proton therapy, there is the possibility of sparing healthy tissue close to the target volume. This is especially important when tumours are located next to critical organs and while treating cancer in paediatric patients. On the other hand, the interactions of protons with matter result in the production of secondary radiation, mostly neutrons and gamma radiation, which deposit their energy at a distance from the target. The aim of this study was to compare the response of different passive dosimetry systems in mixed radiation field induced by proton pencil beam inside anthropomorphic phantoms representing 5 and 10 years old children. Doses were measured in different organs with thermoluminescent (MTS-7, MTS-6 and MCP-N), radiophotoluminescent (GD-352 M and GD-302M), bubble and poly-allyl-diglycol carbonate (PADC) track detectors. Results show that RPL detectors are the less sensitive for neutrons than LiF TLDs and can be applied for in-phantom dosimetry of gamma component. Neutron doses determined using track detectors, bubble detectors and pairs of MTS-7/MTS-6 are consistent within the uncertainty range. This is the first study dealing with measurements on child anthropomorphic phantoms irradiated by a pencil scanning beam technique. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SU-F-T-178: Optimized Design of a Diamond Detector Specifically Dedicated to the Dose Distribution Measurements in Clinical Proton Pencil Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moignier, C; Pomorski, M; Agelou, M

2016-06-15

Purpose: In proton-therapy, pencil beam scanning (PBS) dosimetry presents a real challenge due to the small size of the beam (about 3 to 8 mm in FWHM), the pulsed high dose rate (up to 100 Gy/s) and the proton energy variation (about 30 MeV to 250 MeV). In the framework of French INSERM DEDIPRO project, a specifically dedicated single crystal diamond dosimeter (SCDDo) was developed with the objective of obtaining accurate measurements of the dose distribution in PBS modality. Methods: Monte Carlo simulations with MCNPX were performed. A small proton beam of 5 mm in FWHM was simulated as wellmore » as diamond devices with various size, thickness and holder composition. The calculated doses-to-diamond were compared with the doses-to-water in order to reduce the perturbation effects. Monte-Carlo simulations lead to an optimized SCDDo design for small proton beams dosimetry. Following the optimized design, SCDDos were mounted in water-equivalent holders with electrical connection adapted to standard electrometer. First, SCDDos performances (stability, repeatability, signal-to-background ratio…) were evaluated with conventional photon beams. Then, characterizations (dose linearity, dose rate dependence…) with wide proton beams were performed at proton-therapy center (IC-CPO) from Curie Institute (France) with the passive proton delivery technique, in order to confirm dosimetric requirements. Finally, depth-dose distributions were measured in a water tank, for native and modulated Bragg Peaks with the collimator of 12 cm, and compared to a commercial PPC05 parallel-plate ionization chamber reference detector. Lateral-dose profiles were also measured with the collimator of 5 mm, and compared to a commercial SFD diode. Results: The results show that SCDDo design does not disturb the dose distributions. Conclusion: The experimental dose distributions with the SCDDo are in good agreement with the commercial detectors and no energy dependence was observed with this device configuration.« less

Ion recombination and polarity correction factors for a plane-parallel ionization chamber in a proton scanning beam.

PubMed

Liszka, Małgorzata; Stolarczyk, Liliana; Kłodowska, Magdalena; Kozera, Anna; Krzempek, Dawid; Mojżeszek, Natalia; Pędracka, Anna; Waligórski, Michael Patrick Russell; Olko, Paweł

2018-01-01

To evaluate the effect on charge collection in the ionization chamber (IC) in proton pencil beam scanning (PBS), where the local dose rate may exceed the dose rates encountered in conventional MV therapy by up to three orders of magnitude. We measured values of the ion recombination (k s ) and polarity (k pol ) correction factors in water, for a plane-parallel Markus TM23343 IC, using the cyclotron-based Proteus-235 therapy system with an active proton PBS of energies 30-230 MeV. Values of k s were determined from extrapolation of the saturation curve and the Two-Voltage Method (TVM), for planar fields. We compared our experimental results with those obtained from theoretical calculations. The PBS dose rates were estimated by combining direct IC measurements with results of simulations performed using the FLUKA MC code. Values of k s were also determined by the TVM for uniformly irradiated volumes over different ranges and modulation depths of the proton PBS, with or without range shifter. By measuring charge collection efficiency versus applied IC voltage, we confirmed that, with respect to ion recombination, our proton PBS represents a continuous beam. For a given chamber parameter, e.g., nominal voltage, the value of k s depends on the energy and the dose rate of the proton PBS, reaching c. 0.5% for the TVM, at the dose rate of 13.4 Gy/s. For uniformly irradiated regular volumes, the k s value was significantly smaller, within 0.2% or 0.3% for irradiations with or without range shifter, respectively. Within measurement uncertainty, the average value of k pol , for the Markus TM23343 IC, was close to unity over the whole investigated range of clinical proton beam energies. While no polarity effect was observed for the Markus TM23343 IC in our pencil scanning proton beam system, the effect of volume recombination cannot be ignored. © 2017 American Association of Physicists in Medicine.

Range verification for eye proton therapy based on proton-induced x-ray emissions from implanted metal markers

NASA Astrophysics Data System (ADS)

La Rosa, Vanessa; Kacperek, Andrzej; Royle, Gary; Gibson, Adam

2014-06-01

Metal fiducial markers are often implanted on the back of the eye before proton therapy to improve target localization and reduce patient setup errors. We aim to detect characteristic x-ray emissions from metal targets during proton therapy to verify the treatment range accuracy. Initially gold was chosen for its biocompatibility properties. Proton-induced x-ray emissions (PIXE) from a 15 mm diameter gold marker were detected at different penetration depths of a 59 MeV proton beam at the CATANA proton facility at INFN-LNS (Italy). The Monte Carlo code Geant4 was used to reproduce the experiment and to investigate the effect of different size markers, materials, and the response to both mono-energetic and fully modulated beams. The intensity of the emitted x-rays decreases with decreasing proton energy and thus decreases with depth. If we assume the range to be the depth at which the dose is reduced to 10% of its maximum value and we define the residual range as the distance between the marker and the range of the beam, then the minimum residual range which can be detected with 95% confidence level is the depth at which the PIXE peak is equal to 1.96 σbkg, which is the standard variation of the background noise. With our system and experimental setup this value is 3 mm, when 20 GyE are delivered to a gold marker of 15 mm diameter. Results from silver are more promising. Even when a 5 mm diameter silver marker is placed at a depth equal to the range, the PIXE peak is 2.1 σbkg. Although these quantitative results are dependent on the experimental setup used in this research study, they demonstrate that the real-time analysis of the PIXE emitted by fiducial metal markers can be used to derive beam range. Further analysis are needed to demonstrate the feasibility of the technique in a clinical setup.

TU-G-BRCD-01: Will the High Cost of Proton Therapy Facilities Limit the Availability of Proton Therapy Treatment?

PubMed

Maughan, R

2012-06-01

The potential dose distribution advantages associated with proton therapy, and particularly with pencil beam scanning (PBS) techniques, have lead to considerable interest in this modality in recent years. However, the large capital expenditure necessary for such a project requires careful financial consideration and business planning. The complexity of the beam delivery systems impacts the capital expenditure and the PBS only systems presently being advocated can reduce these costs. Also several manufacturers are considering "one-room" facilities as less expensive alternatives to multi-room facilities. This presentation includes a brief introduction to beam delivery options (passive scattering, uniform and modulated scanning) and some of the new technologies proposed for providing less expensive proton therapy systems. Based on current experience, data on proton therapy center start-up costs, running costs and the financial challenges associated with making this highly conformal therapy more widely available will be discussed. Issues associated with proton therapy implementation that are key to project success include strong project management, vendor cooperation and collaboration, staff recruitment and training. Time management during facility start up is a major concern, particularly in multi-room systems, where time must be shared between continuing vendor system validation, verification and acceptance testing, and user commissioning and patient treatments. The challenges associated with facility operation during this period and beyond are discussed, focusing on how standardization of process, downtime and smart scheduling can influence operational efficiency. 1. To understand the available choices for proton therapy facilities, the different beam delivery systems and the financial implications associated with these choices. 2. To understand the key elements necessary for successfully implementing a proton therapy program. 3. To understand the challenges associated with on-going facility management to achieve an efficient fully operational system. © 2012 American Association of Physicists in Medicine.

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

2014-12-01

Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.

Evaluation of beam delivery and ripple filter design for non-isocentric proton and carbon ion therapy.

PubMed

Grevillot, L; Stock, M; Vatnitsky, S

2015-10-21

This study aims at selecting and evaluating a ripple filter design compatible with non-isocentric proton and carbon ion scanning beam treatment delivery for a compact nozzle. The use of non-isocentric treatments when the patient is shifted as close as possible towards the nozzle exit allows for a reduction in the air gap and thus an improvement in the quality of scanning proton beam treatment delivery. Reducing the air gap is less important for scanning carbon ions, but ripple filters are still necessary for scanning carbon ion beams to reduce the number of energy steps required to deliver homogeneous SOBP. The proper selection of ripple filters also allows a reduction in the possible transverse and depth-dose inhomogeneities that could appear in non-isocentric conditions in particular. A thorough review of existing ripple filter designs over the past 16 years is performed and a design for non-isocentric treatment delivery is presented. A unique ripple filter quality index (QIRiFi) independent of the particle type and energy and representative of the ratio between energy modulation and induced scattering is proposed. The Bragg peak width evaluated at the 80% dose level (BPW80) is proposed to relate the energy modulation of the delivered Bragg peaks and the energy layer step size allowing the production of homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for carbon ion and ripple filter simulations based on measurements performed at CNAO and subsequently used for a detailed analysis of the proposed ripple filter design. A combination of two ripple filters in a series has been validated for non-isocentric delivery and did not show significant transverse and depth-dose inhomogeneities. Non-isocentric conditions allow a significant reduction in the spot size at the patient entrance (up to 350% and 200% for protons and carbon ions with range shifter, respectively), and therefore in the lateral penumbra in the patients.

Stimulating Central Carbon Metabolism to Re-sensitize Pseudomonas aeruginosa to Aminoglycosides.

PubMed

Martins, Dorival; Nguyen, Dao

2017-02-16

In this issue of Cell Chemical Biology, Meylan et al. (2017) examine how stimulation of central carbon metabolism of Pseudomonas aeruginosa modulates aminoglycoside lethality in tolerant bacteria. They identify fumarate as a tobramycin potentiator that stimulates proton motive force-dependent drug uptake and increases respiration-dependent killing. Copyright © 2017. Published by Elsevier Ltd.

Effects of pH adjustment and sodium ions on sour taste intensity of organic acids

USDA-ARS?s Scientific Manuscript database

Protonated organic acid species have been shown to be the primary stimuli responsible for sour taste of organic acids. However, we have observed that sour taste may be modulated when the pH of acid solutions is raised using sodium hydroxide. Objectives were to evaluate the effect of pH adjustment on...

Sentinel Lymph Node Biopsy: Quantification of Lymphedema Risk Reduction

DTIC Science & Technology

2006-10-01

dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J Radiat Oncol Biol Phys...techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast. Radiother Oncol. Feb...Harris JR. Three-dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J

[Clinical experience in image-guided ultra-conformal hypofractionated radiotherapy in case of metastatic diseases at the University of Pécs].

PubMed

László, Zoltán; Boronkai, Árpád; Lõcsei, Zoltán; Kalincsák, Judit; Szappanos, Szabolcs; Farkas, Róbert; Al Farhat, Yousuf; Sebestyén, Zsolt; Sebestyén, Klára; Kovács, Péter; Csapó, László; Mangel, László

2015-06-01

With the development of radiation therapy technology, the utilization of more accurate patient fixation, inclusion of PET/CT image fusion into treatment planning, 3D image-guided radiotherapy, and intensity-modulated dynamic arc irradiation, the application of hypofractionated stereotactic radiotherapy can be extended to specified extracranial target volumes, and so even to the treatment of various metastases. Between October 2012 and August 2014 in our institute we performed extracranial, hypofractionated, image-többguided radiotherapy with RapidArc system for six cases, and 3D conformal multifield technique for one patient with Novalis TX system in case of different few-numbered and slow-growing metastases. For the precise definition of the target volumes we employed PET/CT during the treatment planning procedure. Octreotid scan was applied in one carcinoid tumour patient. Considering the localisation of the metastases and the predictable motion of the organs, we applied 5 to 20 mm safety margin during the contouring procedure. The average treatment volume was 312 cm3. With 2.5-3 Gy fraction doses we delivered 39-45 Gy total dose, and the treatment duration was 2.5 to 3 weeks. The image guidance was carried out via ExacTrac, and kV-Cone Beam CT equipment based on an online protocol, therefore localisation differences were corrected before every single treatment. The patients tolerated the treatments well without major (Gr>2) side effects. Total or near total regression of the metastases was observed at subsequent control examinations in all cases (the median follow-up time was 5 months). According to our first experience, extracranial, imageguided hypofractionated radiotherapy is well-tolerated by patients and can be effectively applied in the treatment of slow-growing and few-numbered metastases.

SU-F-T-344: Commissioning Constant Dose Rate VMAT in the Raystation Treatment Planning System for a Varian Clinac IX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pursley, J; Gueorguiev, G; Prichard, H

Purpose: To demonstrate the commissioning of constant dose rate volumetric modulated arc therapy (VMAT) in the Raystation treatment planning system for a Varian Clinac iX with Exact couch. Methods: Constant dose rate (CDR) VMAT is an option in the Raystation treatment planning system, enabling VMAT delivery on Varian linacs without a RapidArc upgrade. Raystation 4.7 was used to commission CDR-VMAT for a Varian Clinac iX. Raystation arc model parameters were selected to match machine deliverability characteristics. A Varian Exact couch model was added to Raystation 4.7 and commissioned for use in VMAT optimization. CDR-VMAT commissioning checks were performed on themore » linac, including patient-specific QA measurements for 10 test patients using both the ArcCHECK from Sun Nuclear Corporation and COMPASS from IBA Dosimetry. Multi-criteria optimization (MCO) in Raystation was used for CDR-VMAT planning. Results: Raystation 4.7 generated clinically acceptable and deliverable CDR-VMAT plans for the Varian Clinac. VMAT plans were optimized including a model of the Exact couch with both rails in the out positions. CDR-VMAT plans generated with MCO in Raystation were dosimetrically comparable to Raystation MCO-generated IMRT plans. Patient-specific QA measurements with the ArcCHECK on the couch showed good agreement with the treatment planning system prediction. Patient-specific, structure-specific, multi-statistical parameter 3D QA measurements with gantry-mounted COMPASS also showed good agreement. Conclusion: Constant dose rate VMAT was successfully modeled in Raystation 4.7 for a Varian Clinac iX, and Raystation’s multicriteria optimization generated constant dose rate VMAT plans which were deliverable and dosimetrically comparable to IMRT plans.« less

SU-E-T-430: Modeling MLC Leaf End in 2D for Sliding Window IMRT and Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Zhu, T

2014-06-01

Purpose: To develop a 2D geometric model for MLC accounting for leaf end dose leakage for dynamic IMRT and Rapidarc therapy. Methods: Leaf-end dose leakage is one of the problems for MLC dose calculation and modeling. Dosimetric leaf gap used to model the MLC and to count for leakage in dose calculation, but may not be accurate for smaller leaf gaps. We propose another geometric modeling method to compensate for the MLC round-shape leaf ends dose leakage, and improve the accuracy of dose calculation and dose verification. A triangular function is used to geometrically model the MLC leaf end leakagemore » in the leaf motion direction, and a step function is used in the perpendicular direction. Dose measurements with different leaf gap, different window width, and different window height were conducted, and the results were used to fit the analytical model to get the model parameters. Results: Analytical models have been obtained for stop-and-shoot and dynamic modes for MLC motion. Parameters a=0.4, lw'=5.0 mm for 6X and a=0.54, lw'=4.1 mm for 15x were obtained from the fitting process. The proposed MLC leaf end model improves the dose profile at the two ends of the sliding window opening. This improvement is especially significant for smaller sliding window openings, which are commonly used for highly modulated IMRT plans and arc therapy plans. Conclusion: This work models the MLC round leaf end shape and movement pattern for IMRT dose calculation. The theory, as well as the results in this work provides a useful tool for photon beam IMRT dose calculation and verification.« less

Proton therapy - Present and future.

PubMed

Mohan, Radhe; Grosshans, David

2017-01-15

In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses and greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with "passively-scattered proton therapy" (PSPT) or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality. Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost of establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons. Treatment planning and plan evaluation of PSPT and IMPT require special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc. These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of its true potential. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy and reducing the uncertainties through image-guidance, adaptive radiotherapy, further study of biological properties of protons and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giantsoudi, Drosoula, E-mail: dgiantsoudi@mgh.harvard.edu; Seco, Joao; Eaton, Bree R.

Purpose: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. Methods and Materials: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac inmore » the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (−35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. Results: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. Conclusions: Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children.« less

International Space Station (ISS)

NASA Image and Video Library

1997-10-01

The Zvezda Service Module, the first Russian contribution and third element to the International Space Station (ISS), is shown under construction in the Krunichev State Research and Production Facility (KhSC) in Moscow. Russian technicians work on the module shortly after it completed a pressurization test. In the foreground is the forward portion of the module, including the spherical transfer compartment and its three docking ports. The forward port docked with the cornected Functional Cargo Block, followed by Node 1. Launched via a three-stage Proton rocket on July 12, 2000, the Zvezda Service Module serves as the cornerstone for early human habitation of the Station, providing living quarters, life support system, electrical power distribution, data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.

Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

PubMed

Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

2016-08-26

An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Impact of spot size on plan quality of spot scanning proton radiosurgery for peripheral brain lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Dongxu, E-mail: dongxu-wang@uiowa.edu; Dirksen, Blake; Hyer, Daniel E.

Purpose: To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions. Methods: Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP). Results: For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SSmore » plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100–4.49/100) to 6.05/100 (range 1.38/100–11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100–11.5/100) for Cone and 5.22/100 (range 1.37/100–8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322). Conclusions: For treating peripheral brain lesions—where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy—the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (<7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (<70 MeV) is a major technological challenge in commercially available proton therapy systems.« less

SU-E-T-491: Importance of Energy Dependent Protons Per MU Calibration Factors in IMPT Dose Calculations Using Monte Carlo Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randeniya, S; Mirkovic, D; Titt, U

2014-06-01

Purpose: In intensity modulated proton therapy (IMPT), energy dependent, protons per monitor unit (MU) calibration factors are important parameters that determine absolute dose values from energy deposition data obtained from Monte Carlo (MC) simulations. Purpose of this study was to assess the sensitivity of MC-computed absolute dose distributions to the protons/MU calibration factors in IMPT. Methods: A “verification plan” (i.e., treatment beams applied individually to water phantom) of a head and neck patient plan was calculated using MC technique. The patient plan had three beams; one posterior-anterior (PA); two anterior oblique. Dose prescription was 66 Gy in 30 fractions. Ofmore » the total MUs, 58% was delivered in PA beam, 25% and 17% in other two. Energy deposition data obtained from the MC simulation were converted to Gy using energy dependent protons/MU calibrations factors obtained from two methods. First method is based on experimental measurements and MC simulations. Second is based on hand calculations, based on how many ion pairs were produced per proton in the dose monitor and how many ion pairs is equal to 1 MU (vendor recommended method). Dose distributions obtained from method one was compared with those from method two. Results: Average difference of 8% in protons/MU calibration factors between method one and two converted into 27 % difference in absolute dose values for PA beam; although dose distributions preserved the shape of 3D dose distribution qualitatively, they were different quantitatively. For two oblique beams, significant difference in absolute dose was not observed. Conclusion: Results demonstrate that protons/MU calibration factors can have a significant impact on absolute dose values in IMPT depending on the fraction of MUs delivered. When number of MUs increases the effect due to the calibration factors amplify. In determining protons/MU calibration factors, experimental method should be preferred in MC dose calculations. Research supported by National Cancer Institute grant P01CA021239.« less

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de; Bandurska-Luque, Anna; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based onmore » primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.« less

Neuromodulation by Mg2+ and polyamines of excitatory amino acid currents in rodent neurones in culture.

PubMed

Kumamoto, E

1996-12-01

Excitatory amino-acid currents in rodent central neurones are mediated by the activation of glutamate receptors. Ionotropic types of the receptors are divided into alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors, and the former two are collectively called non-NMDA receptors. The NMDA receptor is modulated by a number of endogenous neuromodulators including Mg2+, polyamines, glycine and protons in extracellular solutions. Although it has been generally thought that each of the neuromodulators acts on a distinct site in the NMDA receptor, recent studies have revealed that these actions may be not necessarily independent of each other. The NMDA receptor response is not only inhibited but also potentiated by Mg2+, and the latter action is due to an interaction of a Mg2+ site with either glycine- or proton-binding site. In the presence of polyamines, a tonic inhibition by protons of the NMDA receptor response is relieved, resulting in a potentiation of the response. Alternatively, it has been recently revealed that there are some subtypes of non-NMDA receptors which are negatively modulated by polyamines in either extra- or intra cellular solutions. The difference in polyamine sensitivity among non-NMDA receptors is attributed to a distinction in their constituted subunits. The inhibition of non-NMDA receptor by intracellular polyamines results in inward rectification of the current-voltage relation which is not seen for polyamine-insensitive ones. This polyamine action is not mimicked by intracellular Mg2+.

Monte Carlo calculation of the radiation field at aircraft altitudes.

PubMed

Roesler, S; Heinrich, W; Schraube, H

2002-01-01

Energy spectra of secondary cosmic rays are calculated for aircraft altitudes and a discrete set of solar modulation parameters and rigidity cut-off values covering all possible conditions. The calculations are based on the Monte Carlo code FLUKA and on the most recent information on the interstellar cosmic ray flux including a detailed model of solar modulation. Results are compared to a large variety of experimental data obtained on the ground and aboard aircraft and balloons, such as neutron, proton, and muon spectra and yields of charged particles. Furthermore, particle fluence is converted into ambient dose equivalent and effective dose and the dependence of these quantities on height above sea level, solar modulation, and geographical location is studied. Finally, calculated dose equivalent is compared to results of comprehensive measurements performed aboard aircraft.

International Space Station (ISS)

NASA Image and Video Library

1997-01-01

This photograph, taken by the Boeing Company,shows Boeing technicians preparing to install one of six hatches or doors to the Node 1 (also called Unity), the first U.S. Module for the International Space Station (ISS). The Node 1, or Unity, serves as a cornecting passageway to Space Station modules and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian-built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

International Space Station (ISS)

NASA Image and Video Library

1997-01-01

This photograph, taken by the Boeing Company, shows Boeing technicians preparing to install one of six hatches or doors to the Node 1 (also called Unity), the first U.S. Module for the International Space Station (ISS). The Node 1, or Unity, serves as a cornecting passageway to Space Station modules and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian-built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

Mitochondrial uncoupling, ROS generation and cardioprotection.

PubMed

Cadenas, Susana

2018-05-31

Mitochondrial oxidative phosphorylation is incompletely coupled, since protons translocated to the intermembrane space by specific respiratory complexes of the electron transport chain can return to the mitochondrial matrix independently of the ATP synthase -a process known as proton leak- generating heat instead of ATP. Proton leak across the inner mitochondrial membrane increases the respiration rate and decreases the electrochemical proton gradient (Δp), and is an important mechanism for energy dissipation that accounts for up to 25% of the basal metabolic rate. It is well established that mitochondrial superoxide production is steeply dependent on Δp in isolated mitochondria and, correspondingly, mitochondrial uncoupling has been identified as a cytoprotective strategy under conditions of oxidative stress, including diabetes, drug-resistance in tumor cells, ischemia-reperfusion (IR) injury or aging. Mitochondrial uncoupling proteins (UCPs) are able to lower the efficiency of oxidative phosphorylation and are involved in the control of mitochondrial reactive oxygen species (ROS) production. There is strong evidence that UCP2 and UCP3, the UCP1 homologues expressed in the heart, protect against mitochondrial oxidative damage by reducing the production of ROS. This review first analyzes the relationship between mitochondrial proton leak and ROS generation, and then focuses on the cardioprotective role of chemical uncoupling and uncoupling mediated by UCPs. This includes their protective effects against cardiac IR, a condition known to increase ROS production, and their roles in modulating cardiovascular risk factors such as obesity, diabetes and atherosclerosis. Copyright © 2018. Published by Elsevier B.V.

Push or Pull? Proton Responsive Ligand Effects in Rhenium Tricarbonyl CO 2 Reduction Catalysts

DOE PAGES

Manbeck, Gerald F.; Muckerman, James T.; Szalda, David J.; ...

2015-02-19

Proton responsive ligands offer control of catalytic reactions through modulation of pH-dependent properties, second coordination sphere stabilization of transition states, or by providing a local proton source for multi-proton, multi-electron reactions. Two fac-[ReI(α-diimine)(CO)₃Cl] complexes with α-diimine = 4,4'- (or 6,6'-) dihydroxy-2,2'-bipyridine (4DHBP and 6DHBP) have been prepared and analyzed as electrocatalysts for reduction of carbon dioxide. Consecutive electrochemical reduction of these complexes yields species identical to those obtained by chemical deprotonation. An energetically feasible mechanism for reductive deprotonation is proposed in which the bpy anion is protonated followed by loss of H₂ and 2H⁺. Cyclic voltammetry reveals a two-electron, three-wavemore » system owing to competing EEC and ECE pathways. The chemical step of the ECE pathway might be attributed to the reductive deprotonation. but cannot be distinguished from chloride dissociation. The rate obtained by digital simulation is approximately 8 s⁻¹. Under CO₂, these competing reactions generate a two-slope catalytic waveform with onset potential of –1.65 V vs Ag/AgCl. Reduction of CO₂ to CO by the [ReI (4DHBP–2H⁺)(CO)₃]⁻ suggests the interaction of CO₂ with the deprotonated species or a third reduction followed by catalysis. Conversely, the reduced form of [Re(6DHBP)(CO)₃Cl] converts CO₂ to CO with a single turnover.« less

Exchange-mediated contrast in CEST and spin-lock imaging.

PubMed

Cobb, Jared Guthrie; Li, Ke; Xie, Jingping; Gochberg, Daniel F; Gore, John C

2014-01-01

Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. Simulations and experimental measurements at 9.4 T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. The simulations and experimental measurements confirm that both CEST and R1ρ measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. >2 ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (<2 ppm) and exchange is in the intermediate-to-fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CEST and R1ρ measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1ρ-dependent acquisitions can be employed to selectively portray protons of specific exchange rates. © 2013.

Exchange-Mediated Contrast in CEST and Spin-Lock Imaging

PubMed Central

Cobb, Jared Guthrie; Li, Ke; Xie, Jingping; Gochberg, Daniel F.; Gore, John C.

2014-01-01

PURPOSE Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. METHODS Simulations and experimental measurements at 9.4T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. RESULTS The simulations and experimental measurements confirm that both CEST and R1ρ measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. > 2ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (< 2 ppm) and exchange is in the intermediate to fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CONCLUSION CEST and R1ρ measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1ρ dependent acquisitions can be employed to selectively portray protons of specific exchange rates. PMID:24239335

Silicon Photoelectrode Thermodynamics and Hydrogen Evolution Kinetics Measured by Intensity-Modulated High-Frequency Resistivity Impedance Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Nicholas C.; Carroll, Gerard M.; Pekarek, Ryan T.

Here, we present an impedance technique based on light intensity-modulated high-frequency resistivity (IMHFR) that provides a new way to elucidate both the thermodynamics and kinetics in complex semiconductor photoelectrodes. We apply IMHFR to probe electrode interfacial energetics on oxide-modified semiconductor surfaces frequently used to improve the stability and efficiency of photoelectrochemical water splitting systems. Combined with current density-voltage measurements, the technique quantifies the overpotential for proton reduction relative to its thermodynamic potential in Si photocathodes coated with three oxides (SiO x, TiO 2, and Al 2O 3) and a Pt catalyst. In pH 7 electrolyte, the flatband potentials of TiOmore » 2- and Al 2O 3-coated Si electrodes are negative relative to samples with native SiO x, indicating that SiO x is a better protective layer against oxidative electrochemical corrosion than ALD-deposited crystalline TiO 2 or Al 2O 3. Adding a Pt catalyst to SiO x/Si minimizes proton reduction overpotential losses but at the expense of a reduction in available energy characterized by a more negative flatband potential relative to catalyst-free SiO x/Si.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pfeffer, H.; Saewert, G.

This paper reports on a 6 kV modulator built and installed at Fermilab to drive the electron gun anode for the Tevatron Electron Lens (TEL). The TEL was built with the intention of shifting the individual (anti)proton bunch tunes to even out the tune spread among all 36 bunches with the desire of improving Tevatron integrated luminosity. This modulator is essentially a 6 kV arbitrary waveform generator that enables the TEL to define the electron beam intensity on a bunch-by-bunch basis. A voltage waveform is constructed having a 7 μs duration that corresponds to the tune shift requirements of amore » 12-bunch (anti)proton beam pulse train. This waveform is played out for any one or all three bunch trains in the Tevatron. The programmed waveform voltages transition to different levels at time intervals corresponding to the 395 ns bunch spacing. In addition, complex voltage waveforms can be played out at a sustained rate of 143 kHz over the full 6 kV output range. This paper describes the novel design of the inductive adder topology employing five transformers. It describes the design aspects that minimize switching losses for this multi-kilovolt, high repetition rate and high duty factor application.« less

Silicon Photoelectrode Thermodynamics and Hydrogen Evolution Kinetics Measured by Intensity-Modulated High-Frequency Resistivity Impedance Spectroscopy

DOE PAGES

Anderson, Nicholas C.; Carroll, Gerard M.; Pekarek, Ryan T.; ...

2017-10-05

Here, we present an impedance technique based on light intensity-modulated high-frequency resistivity (IMHFR) that provides a new way to elucidate both the thermodynamics and kinetics in complex semiconductor photoelectrodes. We apply IMHFR to probe electrode interfacial energetics on oxide-modified semiconductor surfaces frequently used to improve the stability and efficiency of photoelectrochemical water splitting systems. Combined with current density-voltage measurements, the technique quantifies the overpotential for proton reduction relative to its thermodynamic potential in Si photocathodes coated with three oxides (SiO x, TiO 2, and Al 2O 3) and a Pt catalyst. In pH 7 electrolyte, the flatband potentials of TiOmore » 2- and Al 2O 3-coated Si electrodes are negative relative to samples with native SiO x, indicating that SiO x is a better protective layer against oxidative electrochemical corrosion than ALD-deposited crystalline TiO 2 or Al 2O 3. Adding a Pt catalyst to SiO x/Si minimizes proton reduction overpotential losses but at the expense of a reduction in available energy characterized by a more negative flatband potential relative to catalyst-free SiO x/Si.« less

Quantitative two-dimensional HSQC experiment for high magnetic field NMR spectrometers

NASA Astrophysics Data System (ADS)

Koskela, Harri; Heikkilä, Outi; Kilpeläinen, Ilkka; Heikkinen, Sami

2010-01-01

The finite RF power available on carbon channel in proton-carbon correlation experiments leads to non-uniform cross peak intensity response across carbon chemical shift range. Several classes of broadband pulses are available that alleviate this problem. Adiabatic pulses provide an excellent magnetization inversion over a large bandwidth, and very recently, novel phase-modulated pulses have been proposed that perform 90° and 180° magnetization rotations with good offset tolerance. Here, we present a study how these broadband pulses (adiabatic and phase-modulated) can improve quantitative application of the heteronuclear single quantum coherence (HSQC) experiment on high magnetic field strength NMR spectrometers. Theoretical and experimental examinations of the quantitative, offset-compensated, CPMG-adjusted HSQC (Q-OCCAHSQC) experiment are presented. The proposed experiment offers a formidable improvement to the offset performance; 13C offset-dependent standard deviation of the peak intensity was below 6% in range of ±20 kHz. This covers the carbon chemical shift range of 150 ppm, which contains the protonated carbons excluding the aldehydes, for 22.3 T NMR magnets. A demonstration of the quantitative analysis of a fasting blood plasma sample obtained from a healthy volunteer is given.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primarymore » amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators.« less

Investigation and Development of Data-Driven D-Region Model for HF Systems Impacts

NASA Technical Reports Server (NTRS)

Eccles, J. V.; Rice, D.; Sojka, J. J.; Hunsucker, R. D.

2002-01-01

Space Environment Corporation (SEC) and RP Consultants (RPC) are to develop and validate a weather-capable D region model for making High Frequency (HF) absorption predictions in support of the HF communications and radar communities. The weather-capable model will assimilate solar and earth space observations from NASA satellites. The model will account for solar-induced impacts on HF absorption, including X-rays, Solar Proton Events (SPE's), and auroral precipitation. The work plan includes: I . Optimize D-region model to quickly obtain ion and electron densities for proper HF absorption calculations. 2. Develop indices-driven modules for D-region ionization sources for low, mid, & high latitudes including X-rays, cosmic rays, auroral precipitation, & solar protons. (Note: solar spectrum & auroral modules already exist). 3. Setup low-cost monitors of existing HF beacons and add one single-frequency beacon. 4. Use PENEX HF-link database with HF monitor data to validate D-region/HF absorption model using climatological ionization drivers. 5. Develop algorithms to assimilate NASA satellite data of solar, interplanetary, and auroral observations into ionization source modules. 6. Use PENEX HF-link & HF-beacon data for skill score comparison of assimilation versus climatological D-region/HF absorption model. Only some satellites are available for the PENEX time period, thus, HF-beacon data is necessary. 7. Use HF beacon monitors to develop HF-link data assimilation algorithms for regional improvement to the D-region/HF absorption model.

Bone Marrow Sparing in Intensity Modulated Proton Therapy for Cervical Cancer: Efficacy and Robustness under Range and Setup Uncertainties

PubMed Central

Dinges, Eric; Felderman, Nicole; McGuire, Sarah; Gross, Brandie; Bhatia, Sudershan; Mott, Sarah; Buatti, John; Wang, Dongxu

2015-01-01

Background and Purpose This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. Material and Methods IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated x-ray therapy (IMRT). Functional bone marrow was identified by 18F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5–40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3mm translational setup errors in all three principal dimensions. Results In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V5GY, 47% for V10Gy, 54% for V20Gy, and 57% for V40Gy, all with p<0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V5Gy, 37% for V10Gy, 41% for V20Gy, and 39% for V40Gy, all with p<0.01. Conclusions The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors. PMID:25981130

Glutaredoxin-2 is required to control proton leak through uncoupling protein-3.

PubMed

Mailloux, Ryan J; Xuan, Jian Ying; Beauchamp, Brittany; Jui, Linda; Lou, Marjorie; Harper, Mary-Ellen

2013-03-22

Glutathionylation has emerged as a key modification required for controlling protein function in response to changes in cell redox status. Recently, we showed that the glutathionylation state of uncoupling protein-3 (UCP3) modulates the leak of protons back into the mitochondrial matrix, thus controlling reactive oxygen species production. However, whether or not UCP3 glutathionylation is mediated enzymatically has remained unknown because previous work relied on the use of pharmacological agents, such as diamide, to alter the UCP3 glutathionylation state. Here, we demonstrate that glutaredoxin-2 (Grx2), a matrix oxidoreductase, is required to glutathionylate and inhibit UCP3. Analysis of bioenergetics in skeletal muscle mitochondria revealed that knock-out of Grx2 (Grx2(-/-)) increased proton leak in a UCP3-dependent manner. These effects were reversed using diamide, a glutathionylation catalyst. Importantly, the increased leak did not compromise coupled respiration. Knockdown of Grx2 augmented proton leak-dependent respiration in primary myotubes from wild type mice, an effect that was absent in UCP3(-/-) cells. These results confirm that Grx2 deactivates UCP3 by glutathionylation. To our knowledge, this is the first enzyme identified to regulate UCP3 by glutathionylation and is the first study on the role of Grx2 in the regulation of energy metabolism.

Dosimetric characterization with 62 MeV protons of a silicon-segmented detector for 2D dose verifications in radiotherapy

NASA Astrophysics Data System (ADS)

Talamonti, C.; Bucciolini, M.; Marrazzo, L.; Menichelli, D.; Bruzzi, M.; Cirrone, G. A. P.; Cuttone, G.; LoJacono, P.

2008-10-01

Due to the features of the modern radiotherapy techniques, namely intensity modulated radiation therapy and proton therapy, where high spatial dose gradients are often present, detectors to be employed for 2D dose verifications have to satisfy very narrow requirements. In particular they have to show high spatial resolution. In the framework of the European Integrated Project—Methods and Advanced Equipment for Simulation and Treatment in Radio-Oncology (MAESTRO, no. LSHC-CT-2004-503564), a dosimetric detector adequate for 2D pre-treatment dose verifications was developed. It is a modular detector, based on a monolithic silicon-segmented sensor, with an n-type implantation on an epitaxial p-type layer. Each pixel element is 2×2 mm 2 and the distance center-to-center is 3 mm. The sensor is composed of 21×21 pixels. In this paper, we report the dosimetric characterization of the system with a proton beam. The sensor was irradiated with 62 MeV protons for clinical treatments at INFN-Laboratori Nazionali del Sud (LNS) Catania. The studied parameters were repeatability of a same pixel, response linearity versus absorbed dose, and dose rate and dependence on field size. The obtained results are promising since the performances are within the project specifications.